Trial Outcomes & Findings for Open Label Extension Study of 1 mg/kg Pegunigalsidase Alfa Every 2 Weeks in Patients With Fabry Disease (NCT NCT03566017)

Last Updated: 2026-03-24

Results Overview

No primary or secondary endpoints were specified for this trial. Evaluation of safety was a main objective. A treatment-emergent adverse event (TEAE) was defined as any adverse event (AE) occurring after the start of study treatment and within the time of residual drug effect (20 days after last administration of study treatment) or a pre-treatment AE or medical condition that worsened in severity after the start of study treatment and within the time of residual drug effect. Each TEAE was classified for severity based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and for causality in the categories unrelated, unlikely, possible, probable and definitely. Treatment-related AEs were TEAEs with causality assessed as possible, probable or definitely related to study treatment. TEAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version (v)19.0. Related TEAEs reported in ≥2 percent of participants by Preferred Term are reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

97 participants

Primary outcome timeframe

From first ever infusion of pegunigalsidase alfa, which could have been in the parent study (PB-102-F01/F20/F30) or this extension study, CLI-06657AA1-04, until 90 days after the final dose visit for each participant. Mean individual exposure: 5.5 years

Results posted on

2026-03-24

Participant Flow

Study CLI-06657AA1-04 was an extension study of studies PB-102-F03, PB-102-F20 and PB-102-F30. Participants who completed studies PB-102-F20 or PB-102-F30 or at least 48 months in study PB-102-F03 and opted to enroll in the extension study were included.

Participant milestones

Participant milestones
Measure	Experimental Open Label pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Overall Study STARTED	97
Overall Study COMPLETED	81
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental Open Label pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Overall Study Withdrawal by Subject	7
Overall Study Adverse Event	5
Overall Study Lost to Follow-up	2
Overall Study Physician Decision	1
Overall Study Advice of physician - disease progression on treatment	1

Baseline Characteristics

Participants in Cohort F03 (those enrolled from study PB-102-F03) were excluded as the plasma Lyso-Gb3 was assessed in different laboratories in studies PB-102-F01/F02/F03 and in studies PB-102-F20, PB-102-F30 and CLI-06657AA1-04. Baseline data were available for 86/87 participants in the Intention-to-Treat (ITT) Population excluding Cohort F03.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Age, Continuous	45.0 years STANDARD_DEVIATION 10.80 • n=97 Participants
Sex: Female, Male Female	37 Participants n=97 Participants
Sex: Female, Male Male	60 Participants n=97 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=97 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	95 Participants n=97 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=97 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=97 Participants
Race (NIH/OMB) Asian	1 Participants n=97 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=97 Participants
Race (NIH/OMB) Black or African American	4 Participants n=97 Participants
Race (NIH/OMB) White	92 Participants n=97 Participants
Race (NIH/OMB) More than one race	0 Participants n=97 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=97 Participants
Fabry disease classification Classic Fabry disease	53 Participants n=97 Participants
Fabry disease classification Non-classic Fabry disease	44 Participants n=97 Participants
Estimated glomerular filtration rate (eGFR)	78.2 mL/min/1.73m^2 STANDARD_DEVIATION 23.27 • n=97 Participants
Plasma globotriaosylsphingosine (Lyso-Gb3) concentration	27.8 nM STANDARD_DEVIATION 30.59 • n=86 Participants • Participants in Cohort F03 (those enrolled from study PB-102-F03) were excluded as the plasma Lyso-Gb3 was assessed in different laboratories in studies PB-102-F01/F02/F03 and in studies PB-102-F20, PB-102-F30 and CLI-06657AA1-04. Baseline data were available for 86/87 participants in the Intention-to-Treat (ITT) Population excluding Cohort F03.
Status of immunoglobulin G (IgG) anti-drug antibodies to pegunigalsidase alfa (ADA) ADA-positive	25 Participants n=97 Participants
Status of immunoglobulin G (IgG) anti-drug antibodies to pegunigalsidase alfa (ADA) ADA-negative	72 Participants n=97 Participants
Urine protein to creatinine ratio (UPCR) > 0.5 g/g UPCR >0.5 to <1 g/g	11 Participants n=97 Participants
Urine protein to creatinine ratio (UPCR) > 0.5 g/g UPCR ≥1 g/g	11 Participants n=97 Participants
Previous treatment with enzyme replacement therapy Agalsidase alfa	18 Participants n=97 Participants
Previous treatment with enzyme replacement therapy Agalsidase beta	69 Participants n=97 Participants
Previous treatment with enzyme replacement therapy None	10 Participants n=97 Participants
Mainz Severity Score Index (MSSI)	23.4 Score on a scale STANDARD_DEVIATION 10.67 • n=97 Participants

PRIMARY outcome

Timeframe: From first ever infusion of pegunigalsidase alfa, which could have been in the parent study (PB-102-F01/F20/F30) or this extension study, CLI-06657AA1-04, until 90 days after the final dose visit for each participant. Mean individual exposure: 5.5 years

Population: Safety Population, which included all participants who provided informed consent for study CLI-06657AA1-04 and received any dose (including a partial dose) of pegunigalsidase alfa in study CLI-06657AA1-04.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Number of Participants With Treatment-related Adverse Events At least one related TEAE	46 Participants
Number of Participants With Treatment-related Adverse Events Infusion related reaction	8 Participants
Number of Participants With Treatment-related Adverse Events Nausea	6 Participants
Number of Participants With Treatment-related Adverse Events Pruritus	5 Participants
Number of Participants With Treatment-related Adverse Events Headache	4 Participants
Number of Participants With Treatment-related Adverse Events Abdominal pain	3 Participants
Number of Participants With Treatment-related Adverse Events Chills	3 Participants
Number of Participants With Treatment-related Adverse Events Dizziness	3 Participants
Number of Participants With Treatment-related Adverse Events Fatigue	3 Participants
Number of Participants With Treatment-related Adverse Events Vomiting	3 Participants
Number of Participants With Treatment-related Adverse Events Body temperature increased	2 Participants
Number of Participants With Treatment-related Adverse Events Chest discomfort	2 Participants
Number of Participants With Treatment-related Adverse Events Diarhoea	2 Participants
Number of Participants With Treatment-related Adverse Events Hypersensitivity	2 Participants
Number of Participants With Treatment-related Adverse Events Infusion site extravasation	2 Participants
Number of Participants With Treatment-related Adverse Events Oedema peripheral	2 Participants
Number of Participants With Treatment-related Adverse Events Paraesthesia	2 Participants
Number of Participants With Treatment-related Adverse Events Peripheral swelling	2 Participants
Number of Participants With Treatment-related Adverse Events Sneezing	2 Participants
Number of Participants With Treatment-related Adverse Events Supraventricular extrasystoles	2 Participants
Number of Participants With Treatment-related Adverse Events Weight increased	2 Participants

SECONDARY outcome

Timeframe: From baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

Population: Intent-to-treat (ITT) Population, which included all participants who provided informed consent for study CLI-06657AA1-04 and received any dose, including a partial dose of pegunigalsidase alfa in study CLI-06657AA1-04.

The eGFR, calculated based on serum creatinine values, according to the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula (2009).

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change From Baseline to the Last Observation for the eGFR	-10.5 mL/min/1.73 m^2 Standard Deviation 12.91

SECONDARY outcome

Timeframe: From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or this extension study, CLI-06657AA1-04), until the end of the extension study; mean individual exposure: 5.5 years

Population: The ITT population, which included all participants who provided informed consent for study CLI-06657AA1-04 and received any dose, including a partial dose of pegunigalsidase alfa in study CLI-06657AA1-04.

The annualized eGFR slope was added in the statistical analysis plan. Individual eGFR slopes were derived for each participant using a linear regression model and summarized descriptively.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Annualized eGFR Slope	-2.2 mL/min/1.73 m^2/year Standard Deviation 3.52

SECONDARY outcome

Timeframe: Shift from baseline (assessment before first exposure to study drug which could be in the parent study PB-102-F01/F02/F30 or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

Population: Shift table was generated. The number of participants in the ITT Population per UPCR category at baseline is presented by row with shifts in UPCR category at the last scheduled visit for each row.

The UPCR was assessed by spot urine test. Participants were categorized according to UPCR at baseline and subsequent visits.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥0.15 to ≤0.5 g/g at baseline · UPCR ≥1 g/g at last scheduled visit	3 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR >0.5 to <1 g/g at baseline · UPCR <0.15 g/g at last scheduled visit	4 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR >0.5 to <1 g/g at baseline · UPCR ≥0.15 to ≤0.5 g/g at last scheduled visit	2 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR >0.5 to <1 g/g at baseline · UPCR >0.5 to <1 g/g at last scheduled visit	2 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR <0.15 g/g at baseline · UPCR <0.15 g/g at last scheduled visit	45 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR <0.15 g/g at baseline · UPCR ≥0.15 to ≤0.5 g/g at last scheduled visit	9 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR <0.15 g/g at baseline · UPCR >0.5 to <1 g/g at last scheduled visit	0 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR <0.15 g/g at baseline · UPCR ≥1 g/g at last scheduled visit	0 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥0.15 to ≤0.5 g/g at baseline · UPCR <0.15 g/g at last scheduled visit	8 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥0.15 to ≤0.5 g/g at baseline · UPCR ≥0.15 to ≤0.5 g/g at last scheduled visit	8 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥0.15 to ≤0.5 g/g at baseline · UPCR >0.5 to <1 g/g at last scheduled visit	2 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR >0.5 to <1 g/g at baseline · UPCR ≥1 g/g at last scheduled visit	3 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥1 g/g at baseline · UPCR <0.15 g/g at last scheduled visit	3 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥1 g/g at baseline · UPCR ≥0.15 to ≤0.5 g/g at last scheduled visit	0 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥1 g/g at baseline · UPCR >0.5 to <1 g/g at last scheduled visit	2 Participants
Shift From Baseline to the Last Scheduled Visit in UPCR Category UPCR ≥1 g/g at baseline · UPCR ≥1 g/g at last scheduled visit	6 Participants

SECONDARY outcome

Timeframe: Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04 ) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

Population: Plasma Lyso-Gb3 was assessed in different laboratories in studies PB-102-F01/F02/F03 and studies PB-102-F20/F30 and CLI-06657AA1-04. Plasma Gb3 was assessed in a different unit in studies PB-102-F01/F02/F03 and and studies PB-102-F20/F30 and CLI-06657AA1-04 and conversion between the units was not possible. Therefore, analyses of changes from baseline were performed in the pooled sample of participants enrolled from studies PB-102-F20 and PB-102-F30 (87 participants).

Plasma concentrations of Lyso-Gb3 and Gb3 (biomarkers for Fabry disease) were assessed at baseline and subsequent time points and change from baseline was assessed.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=87 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change From Baseline to the Last Observation in Plasma Lyso-Gb3 and Globotriaosylceramide (Gb3) Concentrations Plasma Lyso-Gb3 concentration	-1.7 nM Standard Deviation 18.87
Change From Baseline to the Last Observation in Plasma Lyso-Gb3 and Globotriaosylceramide (Gb3) Concentrations Plasma Gb3 concentration	-776.9 nM Standard Deviation 1568.08

SECONDARY outcome

Timeframe: Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

The short form Brief Pain Inventory (BPI) consists of 4 pain severity items (pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on average and current pain) and 7 pain interference items (general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life) assessed over a 24-hour recall period. Each item is rated on a scale from 0 (no pain/interference) to 10 (worst pain imaginable/complete interference). Participants report percentage of pain relief by analgesics over the past 24 hours as well. Assessment of pain (by the BPI) was performed at baseline and subsequent time points.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change From Baseline to the Last Observation for Pain Severity Items of the Brief Pain Inventory (BPI) Pain at its worst in the last 24 hours	-0.3 score on a scale Standard Deviation 2.33
Change From Baseline to the Last Observation for Pain Severity Items of the Brief Pain Inventory (BPI) Pain at its least in the last 24 hours	0.2 score on a scale Standard Deviation 1.77
Change From Baseline to the Last Observation for Pain Severity Items of the Brief Pain Inventory (BPI) Pain right now	0.1 score on a scale Standard Deviation 1.84
Change From Baseline to the Last Observation for Pain Severity Items of the Brief Pain Inventory (BPI) Pain on the average	-0.1 score on a scale Standard Deviation 1.68

SECONDARY outcome

Timeframe: Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

The MSSI represents patients with Fabry disease. Overall scores of \<20, ≥20 and ≤40 and \>40 indicate that patients are mildly, moderately or severely affected, respectively. An increase in the score indicates increased severity of the disease. Symptom assessment by the MSSI was performed at baseline and at subsequent time points. The ranges for the MSSI general, neurological, cardiovascular and renal dysfunction domain scores are 0 to 18, 0 to 20, 0 to 20 and 0 to 18 respectively. The overall score considered for the study is the sum of the domain scores - min 0 max 76

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change From Baseline to the Last Observation in Overall Score for the Mainz Severity Score Index (MSSI)	0.6 score on a scale Standard Deviation 7.94

SECONDARY outcome

Timeframe: Shift from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to 72 months, in number of participants using pain medications (categorized by 0, 1 and 2+ pain medications)

Population: Participants in the ITT population with data available for pain medication use at baseline and at 72 months

At baseline, participants were categorized by the number of pain medications used (0, 1 and 2+ pain medications). Shifts from baseline to 72 months in the number of participants using pain medications (categorized by number of pain medications used) are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=47 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change in Use of Pain Medication During Treatment Participants using 0 pain medication at baseline with data available at 72 months · Participants using 0 pain medication at 72 months	9 Participants
Change in Use of Pain Medication During Treatment Participants using 0 pain medication at baseline with data available at 72 months · Participants using 1 pain medications at 72 months	11 Participants
Change in Use of Pain Medication During Treatment Participants using 0 pain medication at baseline with data available at 72 months · Participants using 2 or more pain medications at 72 months	1 Participants
Change in Use of Pain Medication During Treatment Participants using 1 pain medication at baseline with data available at 72 months · Participants using 0 pain medication at 72 months	0 Participants
Change in Use of Pain Medication During Treatment Participants using 1 pain medication at baseline with data available at 72 months · Participants using 1 pain medications at 72 months	7 Participants
Change in Use of Pain Medication During Treatment Participants using 1 pain medication at baseline with data available at 72 months · Participants using 2 or more pain medications at 72 months	10 Participants
Change in Use of Pain Medication During Treatment Participants using 2 or more pain medications at baseline with data available at 72 months · Participants using 0 pain medication at 72 months	0 Participants
Change in Use of Pain Medication During Treatment Participants using 2 or more pain medications at baseline with data available at 72 months · Participants using 1 pain medications at 72 months	1 Participants
Change in Use of Pain Medication During Treatment Participants using 2 or more pain medications at baseline with data available at 72 months · Participants using 2 or more pain medications at 72 months	8 Participants

SECONDARY outcome

Timeframe: Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

Population: The EQ-5D-5L was not evaluated during study PB-102-F03. Therefore, analysis of change from baseline was performed in a pooled sample of participants from studies PB-102-F20 and PB-102-F30 (ITT Population excluding Cohort F03).

Quality of life was assessed by administering the EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire at baseline and subsequent time points. The assessment includes the EuroQoL-5 Dimensions (EQ-5D) descriptive system and the EQ VAS. For the EQ VAS, participants rated their current health on a vertical VAS which has endpoints labelled 'the best health you can imagine' (score of 100) and 'the worst health you can imagine' (score of 0). An increase in score indicates improvement.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=87 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change From Baseline to the Last Observation in the EuroQoL Visual Analog Scale (EQ VAS) Score	0.9 score on a scale Standard Deviation 17.30

SECONDARY outcome

Timeframe: Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years)

Cardiac assessment was performed by cardiac magnetic resonance imaging (MRI) at baseline and subsequent time points and various parameters including the left ventricular mass index (LVMI) (g/m\^2) with and without hypertrophy were assessed.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change From Baseline to the Last Observation in Left Ventricular Mass Index LVMI with hypertrophy	7.5 g/m^2 Standard Deviation 19.97
Change From Baseline to the Last Observation in Left Ventricular Mass Index LVMI without hypertrophy	9.0 g/m^2 Standard Deviation 11.73

SECONDARY outcome

Timeframe: Baseline (assessment before fist exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or this extension study, CLI-06657AA1-04) to 12 months

Population: Number of participants in the Safety Population (excluding Cohort F03) who had data available for infusion premedication use at baseline and at 12 months.

Infusion premedication use was not collected in studies PB-102-F01/F02/F03. Changes in use of infusion premedication were analyzed in a pooled sample of participants enrolled from studies PB-102-F20 and PB-102-F30. Participants were categorized at baseline by number of infusion premedications used (0, 1, 2 and 3 or more) and shifts from baseline to 12 months in the number of participants using infusion premedications, categorized by number of infusion premedications used, are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=87 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 0 infusion premedication at baseline with data available at 12 months · Participants who used 0 infusion premedication at 12 months	61 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 0 infusion premedication at baseline with data available at 12 months · Participants who used 1 infusion premedication at 12 months	1 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 0 infusion premedication at baseline with data available at 12 months · Participants who used 2 infusion premedications at 12 months	2 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 0 infusion premedication at baseline with data available at 12 months · Participants who used 3 or more infusion premedications at 12 months	1 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 1 infusion premedication at baseline with data available at 12 months · Participants who used 0 infusion premedication at 12 months	6 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 1 infusion premedication at baseline with data available at 12 months · Participants who used 1 infusion premedication at 12 months	3 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 1 infusion premedication at baseline with data available at 12 months · Participants who used 2 infusion premedications at 12 months	0 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 1 infusion premedication at baseline with data available at 12 months · Participants who used 3 or more infusion premedications at 12 months	0 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 2 infusion premedications at baseline with data available at 12 months · Participants who used 0 infusion premedication at 12 months	8 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 2 infusion premedications at baseline with data available at 12 months · Participants who used 1 infusion premedication at 12 months	0 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 2 infusion premedications at baseline with data available at 12 months · Participants who used 2 infusion premedications at 12 months	0 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 2 infusion premedications at baseline with data available at 12 months · Participants who used 3 or more infusion premedications at 12 months	0 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 3 or more infusion premedication at baseline with data available at 12 months · Participants who used 0 infusion premedication at 12 months	3 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 3 or more infusion premedication at baseline with data available at 12 months · Participants who used 1 infusion premedication at 12 months	1 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 3 or more infusion premedication at baseline with data available at 12 months · Participants who used 2 infusion premedications at 12 months	0 Participants
Change in Infusion Premedication Use From Baseline to 12 Months Participants who used 3 or more infusion premedication at baseline with data available at 12 months · Participants who used 3 or more infusion premedications at 12 months	1 Participants

SECONDARY outcome

Timeframe: Baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30 or this extension study, CLI-06657AA1-04) to 24 months

Population: Number of participants in the Safety Population (excluding Cohort F03) who had data available for infusion premedication use at baseline and at 24 months.

Infusion premedication use was not collected in studies PB-102-F01/F02/F03. Changes in use of infusion premedication were analyzed in a pooled sample of participants enrolled from studies PB-102-F20 and PB-102-F30. Participants were categorized at baseline by number of infusion premedications used (0, 1, 2 and 3 or more) and shifts from baseline to 24 months in the number of participants using infusion premedications, categorized by number of infusion premedications used, are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=83 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 0 infusion premedication at baseline with data available at 24 months · Participants who used 0 infusion premedication at 24 months	55 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 0 infusion premedication at baseline with data available at 24 months · Participants who used 1 infusion premedication at 24 months	4 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 0 infusion premedication at baseline with data available at 24 months · Participants who used 2 infusion premedications at 24 months	1 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 0 infusion premedication at baseline with data available at 24 months · Participants who used 3 or more infusion premedication at 24 months	1 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 1 infusion premedication at baseline with data available at 24 months · Participants who used 0 infusion premedication at 24 months	6 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 1 infusion premedication at baseline with data available at 24 months · Participants who used 1 infusion premedication at 24 months	3 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 1 infusion premedication at baseline with data available at 24 months · Participants who used 2 infusion premedications at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 1 infusion premedication at baseline with data available at 24 months · Participants who used 3 or more infusion premedication at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 2 infusion premedications at baseline with data available at 24 months · Participants who used 0 infusion premedication at 24 months	8 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 2 infusion premedications at baseline with data available at 24 months · Participants who used 1 infusion premedication at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 2 infusion premedications at baseline with data available at 24 months · Participants who used 2 infusion premedications at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 2 infusion premedications at baseline with data available at 24 months · Participants who used 3 or more infusion premedication at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 3 or more infusion premedications at baseline with data available at 24 months · Participants who used 0 infusion premedication at 24 months	2 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 3 or more infusion premedications at baseline with data available at 24 months · Participants who used 1 infusion premedication at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 3 or more infusion premedications at baseline with data available at 24 months · Participants who used 2 infusion premedications at 24 months	0 Participants
Change in Infusion Premedication Use From Baseline to 24 Months Participants who used 3 or more infusion premedications at baseline with data available at 24 months · Participants who used 3 or more infusion premedication at 24 months	3 Participants

SECONDARY outcome

Timeframe: Baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30 or this extension study, CLI-06657AA1-04) to 48 months

Population: Number of participants in the Safety Population (excluding Cohort F03) who had data available for infusion premedication use at baseline and at 48 months

Infusion premedication use was not collected in studies PB-102-F01/F02/F03. Changes in use of infusion premedication were analyzed in a pooled sample of participants enrolled from studies PB-102-F20 and PB-102-F30. Participants were categorized at baseline by number of infusion premedications used (0, 1, 2 and 3 or more) and shifts from baseline to 48 months in the number of participants using infusion premedications, categorized by number of infusion premedications used, are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=69 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 2 infusion premedications at baseline with data available at 48 months · Participants who used 1 infusion premedication at 48 months	1 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 2 infusion premedications at baseline with data available at 48 months · Participants who used 2 infusion premedications at 48 months	0 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 2 infusion premedications at baseline with data available at 48 months · Participants who used 3 or more infusion premedications at 48 months	0 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 3 or more infusion premedications at baseline with data available at 48 months · Participants who used 0 infusion premedication at 48 months	2 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 3 or more infusion premedications at baseline with data available at 48 months · Participants who used 1 infusion premedication at 48 months	1 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 3 or more infusion premedications at baseline with data available at 48 months · Participants who used 2 infusion premedications at 48 months	0 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 3 or more infusion premedications at baseline with data available at 48 months · Participants who used 3 or more infusion premedications at 48 months	2 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 0 infusion premedication at baseline with data available at 48 months · Participants who used 0 infusion premedication at 48 months	45 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 0 infusion premedication at baseline with data available at 48 months · Participants who used 1 infusion premedication at 48 months	3 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 0 infusion premedication at baseline with data available at 48 months · Participants who used 2 infusion premedications at 48 months	0 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 0 infusion premedication at baseline with data available at 48 months · Participants who used 3 or more infusion premedications at 48 months	1 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 1 infusion premedication at baseline with data available at 48 months · Participants who used 0 infusion premedication at 48 months	5 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 1 infusion premedication at baseline with data available at 48 months · Participants who used 1 infusion premedication at 48 months	1 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 1 infusion premedication at baseline with data available at 48 months · Participants who used 2 infusion premedications at 48 months	1 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 1 infusion premedication at baseline with data available at 48 months · Participants who used 3 or more infusion premedications at 48 months	0 Participants
Change in Infusion Premedication Use From Baseline to 48 Months Participants who used 2 infusion premedications at baseline with data available at 48 months · Participants who used 0 infusion premedication at 48 months	7 Participants

SECONDARY outcome

Timeframe: Baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30 or this extension study, CLI-06657AA1-04) to 72 months

Population: Number of participants in the Safety Population (excluding Cohort F03) who had data available for infusion premedication use at baseline and at 72 months

Infusion premedication use was not collected in studies PB-102-F01/F02/F03. Changes in use of infusion premedication were analyzed in a pooled sample of participants enrolled from studies PB-102-F20 and PB-102-F30. Participants were categorized at baseline by number of infusion premedications used (0, 1, 2 and 3 or more) and shifts from baseline to 72 months in the number of participants using infusion premedications, categorized by number of infusion premedications used, are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=37 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 0 infusion premedication at baseline with data available at 72 months · Participants who used 0 infusion premedication at 72 months	25 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 0 infusion premedication at baseline with data available at 72 months · Participants who used 1 infusion premedication at 72 months	1 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 0 infusion premedication at baseline with data available at 72 months · Participants who used 2 infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 0 infusion premedication at baseline with data available at 72 months · Participants who used 3 or more infusion premedication at 72 months	1 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 1 infusion premedication at baseline with data available at 72 months · Participants who used 3 or more infusion premedication at 72 months	1 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 2 infusion premedications at baseline with data available at 72 months · Participants who used 0 infusion premedication at 72 months	5 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 2 infusion premedications at baseline with data available at 72 months · Participants who used 1 infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 2 infusion premedications at baseline with data available at 72 months · Participants who used 2 infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 2 infusion premedications at baseline with data available at 72 months · Participants who used 3 or more infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 3 or more infusion premedications at baseline with data available at 72 months · Participants who used 0 infusion premedication at 72 months	1 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 3 or more infusion premedications at baseline with data available at 72 months · Participants who used 1 infusion premedication at 72 months	1 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 3 or more infusion premedications at baseline with data available at 72 months · Participants who used 2 infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 1 infusion premedication at baseline with data available at 72 months · Participants who used 0 infusion premedication at 72 months	2 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 1 infusion premedication at baseline with data available at 72 months · Participants who used 1 infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 1 infusion premedication at baseline with data available at 72 months · Participants who used 2 infusion premedication at 72 months	0 Participants
Change in Infusion Premedication Use From Baseline to 72 Months Participants who used 3 or more infusion premedications at baseline with data available at 72 months · Participants who used 3 or more infusion premedication at 72 months	0 Participants

SECONDARY outcome

Timeframe: From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or in this extension study, CLI-06657AA1-04), until the end of the study. Mean individual exposure was 5.5 years.

The ADA status was assessed as per the schedule of assessments based on sequential evaluation. The participant was considered ADA-positive if IgG screening was presumptive positive and subsequent IgG immunodepletion was positive.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Number of Participants Who Had ADA at Any Post-baseline Visit	47 Participants

SECONDARY outcome

Population: Participants in the Safety Population with treatment-emergent ADA

The ADA status at a visit was decided based on a sequential evaluation as per the schedule of assessments. If the IgG screening was negative, the participant was ADA-negative at that visit. If the IgG screening was presumptive positive, an IgG immunodepletion test was performed and the participant was considered ADA-positive or -negative at the visit based on whether the test was positive or negative. Baseline was the last assessment before the first infusion of pegunigalsidase alfa. Participants were considered to be treatment-emergent ADA-positive if they had titer-boosted or treatment-induced ADA. The ADA were titer-boosted if participants were ADA-positive at baseline and ADA titer had increased by at least 4-fold from baseline during treatment. The ADA were treatment-induced if participants were ADA-negative at baseline and ADA-positive in at least one timepoint post-first infusion.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=31 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Number of Participants With Treatment-emergent ADA Who Had Titer-boosted or Treatment-induced ADA Participants with titer-boosted ADA	7 Participants
Number of Participants With Treatment-emergent ADA Who Had Titer-boosted or Treatment-induced ADA Participants with treatment-induced ADA	24 Participants

SECONDARY outcome

An IRR was defined as a reaction to the infusion of pharmacological and/or biological substances; symptoms could appear within minutes to 2 hours following the end of the infusion and could include pruritus, flushing, swelling, dyspnea, bronchospasm and hypotension. IRRs could be evaluated up to 24 hours from occurrence. Two time frames were considered for IRR analysis: IRR-2H and IRRs occurring during the infusion or within 24 hours after its completion (IRR-24H). All IRR-2H were also classified as IRR-24H. The IRR-2H reported for more than one participant overall by MedDRA PT are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) At least one IRR-2H	23 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Infusion related reaction	7 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Pruritus	4 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Chills	3 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Nausea	2 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Sneezing	2 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Body temperature increased	2 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Dizziness	2 Participants
Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT) Hypersensitivity	2 Participants

SECONDARY outcome

An IRR was defined as a reaction to the infusion of pharmacological and/or biological substances; symptoms could appear within minutes to 2 hours following the end of the infusion and could include pruritus, flushing, swelling, dyspnea, bronchospasm and hypotension. IRRs could be evaluated up to 24 hours from occurrence. Two time frames were considered for IRR analysis: IRR-2H and IRR-24H. All IRR-2H were also classified as IRR-24H. IRR-24H reported for more than one participant overall by MedDRA PT are presented.

Outcome measures

Outcome measures
Measure	Experimental Open Label n=97 Participants pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT At least one IRR-24H	29 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Infusion related reaction	8 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Nausea	4 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Pruritus	4 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Dizziness	2 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Hypersensitivity	2 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Sneezing	2 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Vomiting	2 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Chills	3 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Fatigue	3 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Abdominal pain	2 Participants
Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT Body temperature increased	2 Participants

Adverse Events

Experimental Open Label

Serious events: 45 serious events

Other events: 97 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Experimental Open Label n=97 participants at risk pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Cardiac disorders Acute myocardial infarction	2.1% 2/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Atrial fibrillation	2.1% 2/97 • Number of events 3 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Atrial flutter	2.1% 2/97 • Number of events 3 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Cardiac failure	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Cardiac failure congestive	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Myocardial ischaemia	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Acute coronary syndrome	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Angina pectoris	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Arrhythmia	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Atrioventricular block complete	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Atrioventricular block second degree	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Bradycardia	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Coronary artery disease	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Left ventricular dysfunction	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Sinus arrest	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Ventricular tachycardia	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Congenital, familial and genetic disorders Left ventricular outflow tract obstruction	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Ear and labyrinth disorders Vertigo positional	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Pneumoperitoneum	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Protein-losing gastroenteropathy	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Sudden death	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Chills	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Hypothermia	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Non-cardiac chest pain	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Immune system disorders Anaphylactic reaction	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Cellulitis	3.1% 3/97 • Number of events 3 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Pneumonia	3.1% 3/97 • Number of events 3 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Sepsis	3.1% 3/97 • Number of events 3 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Corona virus infection	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Arthritis bacterial	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Bronchitis	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Clostridial infection	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Infectious mononucleosis	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Meningitis aseptic	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Pyelonephritis	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Septic shock	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Urinary tract infection	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Femur fracture	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Alcohol poisoning	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Clavicle fracture	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Contusion	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Meniscus injury	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Pelvic fracture	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Spinal compression fracture	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Tendon rupture	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Vaccination complication	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Investigations Hepatic enzyme increased	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Investigations Troponin I increased	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Metabolism and nutrition disorders Dehydration	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Osteoarthritis	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Soft tissue mass	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Cerebrovascular accident	3.1% 3/97 • Number of events 3 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Ischaemic stroke	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Syncope	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Cerebral infarction	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Headache	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Loss of consciousness	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Psychiatric disorders Agitation	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Psychiatric disorders Anxiety	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders Chronic kidney disease	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders Acute kidney injury	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders End stage renal disease	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders Renal failure	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Eosinophilic bronchitis	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Surgical and medical procedures Implantable defibrillator insertion	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Surgical and medical procedures Medical device battery replacement	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Surgical and medical procedures Nephrectomy	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Surgical and medical procedures Postoperative care	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Vascular disorders Aortic stenosis	2.1% 2/97 • Number of events 2 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Vascular disorders Extremity necrosis	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Vascular disorders Venous thrombosis limb	1.0% 1/97 • Number of events 1 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).

Other adverse events

Other adverse events
Measure	Experimental Open Label n=97 participants at risk pegunigalsidase alfa pegunigalsidase alfa: Recombinant human alpha galactosidase A
Blood and lymphatic system disorders Anaemia	10.3% 10/97 • Number of events 11 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Atrial fibrillation	12.4% 12/97 • Number of events 20 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Palpitations	11.3% 11/97 • Number of events 14 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Bradycardia	10.3% 10/97 • Number of events 12 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Left ventricular hypertrophy	7.2% 7/97 • Number of events 9 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Bundle branch block right	7.2% 7/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Mitral valve incompetence	7.2% 7/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Bundle branch block left	6.2% 6/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Arrhythmia	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Cardiac disorders Tricuspid valve incompetence	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Ear and labyrinth disorders Hypoacusis	9.3% 9/97 • Number of events 13 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Ear and labyrinth disorders Vertigo	9.3% 9/97 • Number of events 10 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Ear and labyrinth disorders Tinnitus	7.2% 7/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Diarrhoea	22.7% 22/97 • Number of events 37 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Vomiting	20.6% 20/97 • Number of events 28 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Abdominal pain	17.5% 17/97 • Number of events 35 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Nausea	15.5% 15/97 • Number of events 22 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Abdominal discomfort	10.3% 10/97 • Number of events 19 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Gastrooesophageal reflux disease	8.2% 8/97 • Number of events 9 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Abdominal pain upper	7.2% 7/97 • Number of events 11 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Toothache	6.2% 6/97 • Number of events 11 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Dyspepsia	6.2% 6/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Constipation	6.2% 6/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Gastrointestinal disorders Haemorrhoids	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Fatigue	26.8% 26/97 • Number of events 30 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Pyrexia	18.6% 18/97 • Number of events 23 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Oedema peripheral	12.4% 12/97 • Number of events 23 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Infusion site extravasation	10.3% 10/97 • Number of events 18 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Chest pain	8.2% 8/97 • Number of events 15 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Pain	8.2% 8/97 • Number of events 10 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Oedema	7.2% 7/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
General disorders Peripheral swelling	5.2% 5/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Immune system disorders Seasonal allergy	6.2% 6/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Corona virus infection	47.4% 46/97 • Number of events 59 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Nasopharyngitis	36.1% 35/97 • Number of events 74 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Upper respiratory tract infection	23.7% 23/97 • Number of events 43 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Viral infection	19.6% 19/97 • Number of events 25 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Urinary tract infection	17.5% 17/97 • Number of events 18 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Sinusitis	14.4% 14/97 • Number of events 22 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Respiratory tract infection	13.4% 13/97 • Number of events 25 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Influenza	13.4% 13/97 • Number of events 16 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Viral upper respiratory tract infection	11.3% 11/97 • Number of events 22 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Bronchitis	11.3% 11/97 • Number of events 21 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Gastroenteritis viral	8.2% 8/97 • Number of events 10 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Gastroenteritis	7.2% 7/97 • Number of events 11 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Cellulitis	5.2% 5/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Ear infection	5.2% 5/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Infections and infestations Lower respiratory tract infection	5.2% 5/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Infusion related reaction	10.3% 10/97 • Number of events 29 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Vaccination complication	9.3% 9/97 • Number of events 15 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Limb injury	6.2% 6/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Injury, poisoning and procedural complications Contusion	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Investigations Coronavirus test positive	9.3% 9/97 • Number of events 13 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Investigations Blood creatinine increased	8.2% 8/97 • Number of events 12 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Investigations Urine protein/creatinine ratio	7.2% 7/97 • Number of events 9 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Metabolism and nutrition disorders Vitamin D deficiency	7.2% 7/97 • Number of events 8 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Back pain	26.8% 26/97 • Number of events 34 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Pain in extremity	23.7% 23/97 • Number of events 33 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Arthralgia	22.7% 22/97 • Number of events 29 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.3% 11/97 • Number of events 11 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Muscle spasms	8.2% 8/97 • Number of events 12 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Osteoarthritis	5.2% 5/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Musculoskeletal and connective tissue disorders Neck pain	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Headache	29.9% 29/97 • Number of events 52 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Dizziness	16.5% 16/97 • Number of events 27 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Paraesthesia	13.4% 13/97 • Number of events 17 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Migraine	6.2% 6/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Sciatica	5.2% 5/97 • Number of events 8 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Transient ischaemic attack	5.2% 5/97 • Number of events 6 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Nervous system disorders Hypoaesthesia	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Psychiatric disorders Insomnia	9.3% 9/97 • Number of events 12 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Psychiatric disorders Anxiety	8.2% 8/97 • Number of events 10 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Psychiatric disorders Depression	7.2% 7/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders Proteinuria	14.4% 14/97 • Number of events 17 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders Haematuria	10.3% 10/97 • Number of events 13 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Renal and urinary disorders Renal impairment	5.2% 5/97 • Number of events 7 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Cough	28.9% 28/97 • Number of events 39 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	17.5% 17/97 • Number of events 23 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.4% 13/97 • Number of events 15 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.2% 6/97 • Number of events 15 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.2% 6/97 • Number of events 9 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	5.2% 5/97 • Number of events 8 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Skin and subcutaneous tissue disorders Rash	14.4% 14/97 • Number of events 26 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Skin and subcutaneous tissue disorders Pruritus	8.2% 8/97 • Number of events 9 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Skin and subcutaneous tissue disorders Erythema	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Vascular disorders Hypertension	8.2% 8/97 • Number of events 11 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).
Vascular disorders Hypotension	5.2% 5/97 • Number of events 5 • From first infusion until 90 days following the final visit dose for each participant. Mean (SD) individual exposure to study treatment was 5.5 (1.96) years. Each participant was questioned about AEs. The Investigator reported all AEs (directly observed or spontaneously reported by the participant).

Additional Information

Clinical Trial Transparency

Chiesi Farmaceutici S.p.A.

Phone: +3905212791

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any information relating to the study product or the study including any data and results from the study is the exclusive property of the Sponsor. The Investigator and any other persons involved in the study must protect the confidentiality of the proprietary information belonging to Chiesi Farmaceutici S.p.A. The Investigator should ensure that confidentiality of participants' data is preserved.
Publication restrictions are in place

Restriction type: OTHER