Trial Outcomes & Findings for Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks (NCT NCT04739059)

NCT ID: NCT04739059

Last Updated: 2026-06-02

Results Overview

The percentage of participants was rounded to one place of decimal.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

171 participants

Primary outcome timeframe

Approximately up to 54 months

Results posted on

2026-06-02

Participant Flow

This study was conducted at 44 sites in 14 countries (Australia, Canada, Czechia, Germany, Hong Kong, Hungary, Israel, Japan, Netherlands, New Zealand, Russia, Spain, Taiwan, and United States of America).

Total of 171 participants provided informed consent, of which 92 were rolled over from prior studies (CSL312\_2001 and CSL312\_3001) and 79 were treatment-naive. Of 79 participants, 2 failed screening and 77 entered the run-in period. Only 69 participants completed the run-in period. Total of 8 participants discontinued during run-in period: 1 participated less than 1 month, 5 had insufficient HAE attacks, 1 discontinued due to a laboratory abnormality, and 1 discontinued for other reason.

Participant milestones

Participant milestones
Measure
CSL312 (Garadacimab)
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg subcutaneously (SC) once monthly. The treatment-naive (newly enrolled) participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Overall Study
STARTED
161
Overall Study
COMPLETED
146
Overall Study
NOT COMPLETED
15

Reasons for withdrawal

Reasons for withdrawal
Measure
CSL312 (Garadacimab)
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg subcutaneously (SC) once monthly. The treatment-naive (newly enrolled) participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Overall Study
Adverse Event
4
Overall Study
Pregnancy
1
Overall Study
Lack of Efficacy
1
Overall Study
Lost to Follow-up
1
Overall Study
Withdrawal by Subject
3
Overall Study
Physician Decision
2
Overall Study
Site Terminated by Sponsor due to war
3

Baseline Characteristics

Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Age, Continuous
42.3 Years
STANDARD_DEVIATION 15.31 • n=9 Participants
Age, Customized
<=18 years
12 Participants
n=9 Participants
Age, Customized
Between 18 and 64 years
134 Participants
n=9 Participants
Age, Customized
>=65 years
15 Participants
n=9 Participants
Sex: Female, Male
Female
101 Participants
n=9 Participants
Sex: Female, Male
Male
60 Participants
n=9 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
9 Participants
n=9 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
150 Participants
n=9 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants
n=9 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=9 Participants
Race (NIH/OMB)
Asian
22 Participants
n=9 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=9 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=9 Participants
Race (NIH/OMB)
White
135 Participants
n=9 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=9 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
n=9 Participants

PRIMARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the ATP analysis set who received at least one dose of investigational product (IP), and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=159 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants With Treatment-emergent Adverse Events (TEAE)
146 Participants

PRIMARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the ATP analysis set who received at least one dose of IP, and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

The percentage of participants was rounded to one place of decimal.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=159 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants With TEAE
91.8 Percentage of participants

PRIMARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the ATP analysis set who received at least one dose of IP, and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=159 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of TEAE
1196 Events

PRIMARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the ATP analysis set who received at least one dose of IP, and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

The TEAE rate per injection was calculated as the number of TEAE/ total number of injections. The number of injections was defined as the total injections received by participants during the respective safety evaluation period.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=159 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
TEAE Rates Per Injection
0.20 Number of TEAE per injection

PRIMARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the ATP analysis set who received at least one dose of IP, and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

The TEAE rate per participant year was calculated as the total number of TEAE/ participant years. Participant years was defined as the sum of the time (in years) that participant were exposed to study treatment during the respective safety evaluation period.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=159 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
TEAE Rates Per Participant Year
2.26 Number of TEAE per participant year

SECONDARY outcome

Timeframe: Run-in Period: Up to Day 60 and Treatment Period: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\]\*30.4375.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
The Time-normalized Number (Per Month) of Hereditary Angioedema (HAE) Attacks During the Run-in Period and Treatment Period
Per month (Run-in Period)
2.85 Number of HAE attacks per month
Interval 2.61 to 3.17
The Time-normalized Number (Per Month) of Hereditary Angioedema (HAE) Attacks During the Run-in Period and Treatment Period
Per month (Treatment Period)
0.02 Number of HAE attacks per month
Interval 0.0 to 0.02

SECONDARY outcome

Timeframe: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

Time-normalized number of HAE attacks per year during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\]\*365.25.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
The Time-normalized Number (Per Year) of HAE Attacks During Treatment Period
0.25 Number of HAE attacks per year
Interval 0.0 to 0.28

SECONDARY outcome

Timeframe: Run-in Period: Up to 60 days and Treatment Period: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

The percentage reduction in the time-normalized number of HAE attacks was calculated within a participant as: 100\*(1- time normalized number of HAE attacks per month during Treatment Period/time-normalized number of HAE attacks per month during Run-in Period).

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage Reduction in the Attack Rate During the Treatment Period Compared to the Run-in Period
95.41 Percentage reduction in HAE attacks
Standard Deviation 11.073

SECONDARY outcome

Timeframe: Run-in Period: Up to Day 60 and Treatment Period: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

The number of participants who achieved a percentage reduction in HAE attacks of \>=50% (also considered as responders), \>=70%, \>=90%, and 100% (attack free) during the Treatment Period compared with the Run-in Period. The percentage reduction in the time-normalized number of HAE attacks per month was calculated as 100\*\[1 - (time-normalized number of HAE attacks per month under CSL312 treatment / time-normalized number of HAE attacks per month during Run-in Period)\].

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants With Percentage Reduction (of >=50%, >=70%, >=90%, and 100%) in HAE Attacks
>= 50%
158 Participants
Number of Participants With Percentage Reduction (of >=50%, >=70%, >=90%, and 100%) in HAE Attacks
>= 70%
155 Participants
Number of Participants With Percentage Reduction (of >=50%, >=70%, >=90%, and 100%) in HAE Attacks
>= 90%
139 Participants
Number of Participants With Percentage Reduction (of >=50%, >=70%, >=90%, and 100%) in HAE Attacks
Attack free (Reduction of 100%)
76 Participants

SECONDARY outcome

Timeframe: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

Time-normalized number of HAE attacks per month requiring on demand treatment was calculated per participant as: \[number of HAE attacks requiring on demand treatment during treatment period / length of participant treatment in days\]\*30.4375.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
The Time-normalized Number (Per Month) of HAE Attacks Requiring On-demand Treatment
0.00 Number of HAE attacks per month
Interval 0.0 to 0.02

SECONDARY outcome

Timeframe: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

Time-normalized number of HAE attacks requiring on demand treatment per year was calculated per participant as: \[number of HAE attacks requiring on demand treatment during treatment period / length of participant treatment in days\]\*365.25.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
The Time-normalized Number (Per Year) of HAE Attacks Requiring On-demand Treatment
0.00 Number of HAE attacks per year
Interval 0.0 to 0.25

SECONDARY outcome

Timeframe: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks / length of participant treatment in days\]\*30.4375.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
The Time-normalized Number (Per Month) of Moderate and/or Severe HAE Attacks
0.00 Number of HAE attacks per month
Interval 0.0 to 0.02

SECONDARY outcome

Timeframe: Approximately up to 52 months

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment.

Time-normalized number of moderate or severe HAE attacks per year during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks /length of participant treatment in days\]\*365.25.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
The Time-normalized Number (Per Year) of Moderate and/or Severe HAE Attacks
0.00 Number of HAE attacks per year
Interval 0.0 to 0.23

SECONDARY outcome

Timeframe: At Months 12, 24, and 36

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment. The 'number analyzed' represents the participants with available data for each specified category.

Number of participants rating their response to therapy as good or excellent was evaluated as per Subject's Global Assessment of Response to Therapy (SGART) questionnaire. SGART is a patient-reported outcome that represents the participant's overall response to treatment using the following ratings: (0) none: worse or no response at all, not acceptable, (1) poor: very little response, not acceptable, (2) fair: some response, acceptable but could be better, (3) good: good response, acceptable, and (4) excellent: excellent response, as good as can be imagined. Cumulative responses as "Good or Excellent" are reported for this outcome measure.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants Rating Their Response to Therapy as Good or Excellent
At Month 12
136 Participants
Number of Participants Rating Their Response to Therapy as Good or Excellent
At Month 24
130 Participants
Number of Participants Rating Their Response to Therapy as Good or Excellent
At Month 36
108 Participants

SECONDARY outcome

Timeframe: At Months 12, 24, and 36

Population: Analysis was performed on the ATP analysis set which consisted of all participants in the Screened analysis set who were assigned to treatment. The 'number analyzed' represents the participants with available data for each specified category.

Percentage of participants rating their response to therapy as good or excellent was evaluated as per SGART questionnaire. SGART is a patient-reported outcome that represents the participant's overall response to treatment using the following ratings: (0) none: worse or no response at all, not acceptable, (1) poor: very little response, not acceptable, (2) fair: some response, acceptable but could be better, (3) good: good response, acceptable, and (4) excellent: excellent response, as good as can be imagined. Cumulative responses as "Good or Excellent" are reported for this outcome measure. The percentage of participants was rounded to one place of decimal.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants Rating Their Response to Therapy as Good or Excellent
At Month 12
93.8 Percentage of Participants
Percentage of Participants Rating Their Response to Therapy as Good or Excellent
At Month 24
97.7 Percentage of Participants
Percentage of Participants Rating Their Response to Therapy as Good or Excellent
At Month 36
94.7 Percentage of Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
SAE
14 Participants
Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
Experiencing Death
0 Participants
Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
Related TEAE
24 Participants
Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
TEAE leading to study discontinuation
4 Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

The percentage of participants was rounded to one decimal place.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
SAE
8.7 Percentage of participants
Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
Experiencing Death
0 Percentage of participants
Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
Related TEAE
14.9 Percentage of participants
Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation
TEAE leading to study discontinuation
2.5 Percentage of participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Severity of AE was assessed by the investigator and categorized as mild, moderate and severe. A mild AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. A moderate AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. A severe AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants Experiencing TEAE by Severity
Mild
121 Participants
Number of Participants Experiencing TEAE by Severity
Moderate
111 Participants
Number of Participants Experiencing TEAE by Severity
Severe
20 Participants
Number of Participants Experiencing TEAE by Severity
Missing
1 Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Severity of AE was assessed by the investigator and categorized as mild, moderate and severe. A mild AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. A moderate AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. A severe AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention. The percentage of participants was rounded to one decimal place.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants Experiencing TEAE by Severity
Mild
75.2 Percentage of participants
Percentage of Participants Experiencing TEAE by Severity
Moderate
68.9 Percentage of participants
Percentage of Participants Experiencing TEAE by Severity
Severe
12.4 Percentage of participants
Percentage of Participants Experiencing TEAE by Severity
Missing
0.6 Percentage of participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

The AESI defined for this study were thromboembolic events, abnormal bleeding events, and severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants Experiencing Adverse Events of Special Interest (AESI)
Thromboembolic events (Investigator)
0 Participants
Number of Participants Experiencing Adverse Events of Special Interest (AESI)
Abnormal bleeding events (Investigator)
0 Participants
Number of Participants Experiencing Adverse Events of Special Interest (AESI)
Hypersensitivity including anaphylaxis (Investigator)
0 Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

The AESI defined for this study were thromboembolic events, abnormal bleeding events, and severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants Experiencing AESI
Thromboembolic events (Investigator)
0 Percenatge of participants
Percentage of Participants Experiencing AESI
Abnormal bleeding events (Investigator)
0 Percenatge of participants
Percentage of Participants Experiencing AESI
Hypersensitivity including anaphylaxis (Investigator)
0 Percenatge of participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants With Laboratory Findings Reported as TEAE
Urinary occult blood positive
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Urinary sediment present
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Urinary tract infection
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Urine analysis abnormal
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Hyperbilirubinaemia
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Urine ketone body present
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Lymphocyte count decreased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Neutrophil count decreased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Nitrite urine present
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Platelet count increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Protein urine present
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Specific gravity urine increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Thrombocytopenia
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Bacterial test positive
6 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Urinary squamous epithelial cells increased
4 Participants
Number of Participants With Laboratory Findings Reported as TEAE
White blood cells urine positive
2 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Crystal urine present
2 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Red blood cells urine positive
2 Participants
Number of Participants With Laboratory Findings Reported as TEAE
White blood cell count increased
2 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Neutrophil count increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Bilirubin conjugated increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Blood bilirubin increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Blood calcium decreased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Blood creatinine increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Crystalluria
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Cystitis
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Fibrin D dimer increased
1 Participants
Number of Participants With Laboratory Findings Reported as TEAE
Gastroenteritis
1 Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

The percentage of participant was rounded to one place of decimal.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants With Laboratory Findings Reported as TEAE
Blood creatinine increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Crystalluria
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Cystitis
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Fibrin D dimer increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Gastroenteritis
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Hyperbilirubinaemia
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Lymphocyte count decreased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Neutrophil count decreased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Nitrite urine present
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Platelet count increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Protein urine present
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Specific gravity urine increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Thrombocytopenia
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Urinary occult blood positive
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Urinary sediment present
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Urinary tract infection
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Urine ketone body present
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Bacterial test positive
3.7 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Urinary squamous epithelial cells increased
2.5 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
White blood cells urine positive
1.2 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Crystal urine present
1.2 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Red blood cells urine positive
1.2 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
White blood cell count increased
1.2 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Neutrophil count increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Bilirubin conjugated increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Blood bilirubin increased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Blood calcium decreased
0.6 Percentage of Participants
Percentage of Participants With Laboratory Findings Reported as TEAE
Urine analysis abnormal
0.6 Percentage of Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=2 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants With Normal C1-esterase Inhibitor (nC1-INH) Experiencing TEAE
2 Participants

SECONDARY outcome

Timeframe: Approximately up to 54 months

Population: Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received. Here, 'overall number of participants analyzed' = participants with available data for this endpoint.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=2 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants With nC1-INH Experiencing TEAE
100 Percenatge of participants

SECONDARY outcome

Timeframe: At Day 1, Months 6, 12, 36 and 43 (end of treatment [EOT])

Population: Analysis was performed on the Safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Number of Participants With Anti-CSL312 Antibodies
Day 1: Positive
1 Participants
Number of Participants With Anti-CSL312 Antibodies
Month 6: Positive
1 Participants
Number of Participants With Anti-CSL312 Antibodies
Month 12: Positive
4 Participants
Number of Participants With Anti-CSL312 Antibodies
Month 24: Positive
0 Participants
Number of Participants With Anti-CSL312 Antibodies
Month 36: Positive
0 Participants
Number of Participants With Anti-CSL312 Antibodies
EOT: Positive
2 Participants

SECONDARY outcome

Timeframe: At Day 1, Months 6, 12, 36 and 43 (EOT)

Population: Analysis was performed on the Safety analysis set which included all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

The percentage of participants was rounded to one decimal place.

Outcome measures

Outcome measures
Measure
CSL312 (Garadacimab)
n=161 Participants
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Percentage of Participants With Anti-CSL312 Antibodies
Day 1: Positive
0.6 Percentage of participants
Percentage of Participants With Anti-CSL312 Antibodies
Month 6: Positive
0.6 Percentage of participants
Percentage of Participants With Anti-CSL312 Antibodies
Month 12: Positive
2.5 Percentage of participants
Percentage of Participants With Anti-CSL312 Antibodies
Month 24: Positive
0 Percentage of participants
Percentage of Participants With Anti-CSL312 Antibodies
Month 36: Positive
0 Percentage of participants
Percentage of Participants With Anti-CSL312 Antibodies
EOT: Positive
1.2 Percentage of participants

Adverse Events

CSL312 (Garadacimab)

Serious events: 14 serious events
Other events: 147 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
CSL312 (Garadacimab)
n=161 participants at risk
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Infections and infestations
COVID-19
1.2%
2/161 • Number of events 2 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Appendicitis perforated
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Gastroenteritis
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Gastroenteritis viral
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Sinusitis
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Injury, poisoning and procedural complications
Craniofacial injury
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Injury, poisoning and procedural complications
Hand fracture
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Congenital, familial and genetic disorders
Hereditary angioedema
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Gastrointestinal disorders
Abdominal incarcerated hernia
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Immune system disorders
Food allergy
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Metabolism and nutrition disorders
Dehydration
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Nervous system disorders
Radiculopathy
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Skin and subcutaneous tissue disorders
Drug eruption
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Vascular disorders
Hypotension
0.62%
1/161 • Number of events 1 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Other adverse events

Other adverse events
Measure
CSL312 (Garadacimab)
n=161 participants at risk
Participants who rolled over from previous CSL312 (garadacimab) studies into this study received CSL312 at 200 mg SC once monthly. The treatment-naive participants received a loading dose of 400 mg (two 200 mg) CSL312 in the first month, followed by 200 mg CSL312 once monthly in subsequent months.
Infections and infestations
COVID-19
41.6%
67/161 • Number of events 86 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Nasopharyngitis
28.0%
45/161 • Number of events 102 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Influenza
10.6%
17/161 • Number of events 20 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Upper respiratory tract infection
8.7%
14/161 • Number of events 17 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Sinusitis
6.2%
10/161 • Number of events 13 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Gastrointestinal disorders
Abdominal pain
6.8%
11/161 • Number of events 24 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
General disorders
Injection site erythema
8.1%
13/161 • Number of events 18 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Musculoskeletal and connective tissue disorders
Arthralgia
8.1%
13/161 • Number of events 20 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Musculoskeletal and connective tissue disorders
Back Pain
6.2%
10/161 • Number of events 12 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Injury, poisoning and procedural complications
Fall
5.6%
9/161 • Number of events 10 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Nervous system disorders
Headache
9.3%
15/161 • Number of events 25 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Gastroenteritis
5.0%
8/161 • Number of events 8 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Infections and infestations
Urinary tract infection
5.0%
8/161 • Number of events 9 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Gastrointestinal disorders
Toothache
6.8%
11/161 • Number of events 19 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Gastrointestinal disorders
Diarrhoea
5.6%
9/161 • Number of events 9 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Injury, poisoning and procedural complications
Contusion
5.0%
8/161 • Number of events 10 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.
Respiratory, thoracic and mediastinal disorders
Cough
6.2%
10/161 • Number of events 12 • Approximately up to 54 months
Analysis was performed on the Safety analysis set which consisted of all participants in the all treated participants analysis set who received at least 1 dose of IP, and were analyzed using the actual treatment received.

Additional Information

Clinical Study Disclosure Manager

CSL Behring

Phone: 1-610-878-4697

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place