Trial Outcomes & Findings for Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension (NCT NCT03001414)

NCT ID: NCT03001414

Last Updated: 2025-01-31

Results Overview

Change was calculated as the distance walked at 6 months minus the distance at baseline.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

22 participants

Primary outcome timeframe

Baseline, 6 months

Results posted on

2025-01-31

Participant Flow

Participants were recruited based on physician referral from specialized Pulmonary Arterial Hypertension clinics at 6 participating study sites between October 2017 and August 2022. The first participant was enrolled on November 24, 2017 and the last participant was enrolled on August 24, 2022.

Of 22 enrolled participants, 12 met the required inclusion criteria and were randomized to receive treatment with the study product.

Participant milestones

Participant milestones
Measure	Arm 1 - Placebo Followed by Autologous Endothelial Progenitor Cells (EPCs) Transfected With eNOS 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1 followed by 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 2 Placebo followed by Autologous EPCs transfected with human eNOS: 4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months	Arm 2 - Autologous EPCs Transfected With Endothelial NO-synthase (eNOS) Followed by Placebo 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 1 followed by 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 2 Autologous EPCs transfected with human eNOS followed by Placebo: 4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months	Arm 3 - Autologous EPCs Transfected With eNOS 4 monthly IV injections of Autologous EPCs transfected with human eNOS in Course 1 followed by 4 monthly injections of Autologous EPCs transfected with human eNOS in Course 2 (total of 160 million cells) Autologous EPCs transfected with human eNOS: 4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months
Overall Study STARTED	5	3	4
Overall Study COMPLETED	5	3	4
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Followed by Autologous EPCs Transfected With eNOS n=5 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1 followed by 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 2 Placebo followed by Autologous EPCs transfected with human eNOS: 4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months	Autologous EPCs Transfected With eNOS Followed by Placebo n=3 Participants 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 1 followed by 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 2 Autologous EPCs transfected with human eNOS followed by Placebo: 4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months	Autologous EPCs Transfected With eNOS n=4 Participants 4 monthly IV injections of Autologous EPCs transfected with human eNOS in Course 1 followed by 4 monthly injections of Autologous EPCs transfected with human eNOS in Course 2 (total of 160 million cells) Autologous EPCs transfected with human eNOS: 4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months	Total n=12 Participants Total of all reporting groups
Age, Continuous	59.6 Years STANDARD_DEVIATION 15.4 • n=99 Participants	48.7 Years STANDARD_DEVIATION 5.8 • n=107 Participants	55 Years STANDARD_DEVIATION 4.3 • n=206 Participants	55.3 Years STANDARD_DEVIATION 10.9 • n=7 Participants
Sex: Female, Male Female	4 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants	10 Participants n=7 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants
Race/Ethnicity, Customized Caucasian	4 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants	10 Participants n=7 Participants
Race/Ethnicity, Customized Indigenous	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Pulmonary arterial hypertension (PAH) Diagnosis Idopathic/Hereditable	3 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	7 Participants n=7 Participants
Pulmonary arterial hypertension (PAH) Diagnosis Drugs/Toxins	2 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	3 Participants n=7 Participants
Pulmonary arterial hypertension (PAH) Diagnosis Congenital Heart Defects	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants
Oxygen Saturation	93.4 Percent STANDARD_DEVIATION 3.7 • n=99 Participants	95.0 Percent STANDARD_DEVIATION 3.0 • n=107 Participants	95.0 Percent STANDARD_DEVIATION 3.6 • n=206 Participants	94.3 Percent STANDARD_DEVIATION 3.3 • n=7 Participants
6 Minute Walk Test Distance	345.4 Meters STANDARD_DEVIATION 71.48 • n=99 Participants	381.0 Meters STANDARD_DEVIATION 11.53 • n=107 Participants	329.25 Meters STANDARD_DEVIATION 78.08 • n=206 Participants	348.92 Meters STANDARD_DEVIATION 60.57 • n=7 Participants
Concurrent Medications PDE5 Inhibitor	4 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	7 Participants n=7 Participants
Concurrent Medications Endothelin Receptor Antagonist	3 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants	10 Participants n=7 Participants
Concurrent Medications Soluble GC Stimulator	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Concurrent Medications Prostaglandin Intravenous	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Concurrent Medications Dual Therapy	3 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	6 Participants n=7 Participants
Concurrent Medications Triple Therapy	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	4 Participants n=7 Participants
Comorbidities Hypertension	2 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	3 Participants n=7 Participants
Comorbidities Asthma	2 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	3 Participants n=7 Participants
Comorbidities Emphysema	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Comorbidities Obstructive Sleep Apnea	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Comorbidities Gastrointestinal Reflux	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants	6 Participants n=7 Participants
Comorbidities Type 2 Diabetes	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Comorbidities Hypothyroidism	2 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Comorbidities Morbid Obesity	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Comorbidities Seasonal Allergies	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Hemodynamic Parameters Mean pulmonary arterial pressure (PAP) (mmHg)	79 mmHg STANDARD_DEVIATION 13 • n=99 Participants	74 mmHg STANDARD_DEVIATION 4 • n=107 Participants	80 mmHg STANDARD_DEVIATION 15 • n=206 Participants	78 mmHg STANDARD_DEVIATION 11 • n=7 Participants
Hemodynamic Parameters PCWP (mmHg)	11 mmHg STANDARD_DEVIATION 6 • n=99 Participants	9.7 mmHg STANDARD_DEVIATION 7.2 • n=107 Participants	8.5 mmHg STANDARD_DEVIATION 4.8 • n=206 Participants	9.9 mmHg STANDARD_DEVIATION 5.5 • n=7 Participants
Cardiac Output	5.39 L/min STANDARD_DEVIATION 1.36 • n=99 Participants	4.55 L/min STANDARD_DEVIATION 0.41 • n=107 Participants	5.25 L/min STANDARD_DEVIATION 2.26 • n=206 Participants	5.13 L/min STANDARD_DEVIATION 1.49 • n=7 Participants
Pulmonary vascular resistance (PVR)	6.18 WU STANDARD_DEVIATION 2.87 • n=99 Participants	7.87 WU STANDARD_DEVIATION 2.87 • n=107 Participants	7.95 WU STANDARD_DEVIATION 3.26 • n=206 Participants	7.19 WU STANDARD_DEVIATION 2.78 • n=7 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Population: All participants for whom the 6MWD test was completed at baseline and 6 months.

Change was calculated as the distance walked at 6 months minus the distance at baseline.

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=5 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months n=7 Participants 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in 6 Minute Walk Distance (6MWD) From Baseline	22.3 Meters Standard Deviation 38.49	36.00 Meters Standard Deviation 31.11

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: All participants in Arm 2 and 3 for whom the 6MWD test results were recorded at baseline and 12 months.

Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arms 2 versus Arm 3). Change was calculated by the distance walked at 12 months minus the distance walked at baseline.

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=3 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months n=4 Participants 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in 6 Minute Walk Distance (6MWD) From Baseline	49.3 Meters Standard Deviation 11.68	7.33 Meters Standard Deviation 9.02

SECONDARY outcome

Timeframe: Baseline, 6 months, 12 months

Population: All participants in Arm 2 for whom the 6MWD test results were recorded at baseline, 6 months, and 12 months.

Comparison of change from baseline to assess durability of any measured improvement (Arm 2 only). Durability of any improvement at 3 versus 9 months post-treatment (measured at 6 and 12 months).

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=3 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in 6 Minute Walk Distance (6MWD) From Baseline Change from baseline to 6 months	47.3 Meters Standard Deviation 32.50	—
Change in 6 Minute Walk Distance (6MWD) From Baseline Change from baseline to 12 months	49.3 Meters Standard Deviation 11.68	—

SECONDARY outcome

Timeframe: Baseline, 6 months, 12 months

Population: Change was calculated as the distance at 6 months minus the distance at baseline and the distance at 12 months minus the distance at baseline

Incremental effect of 8 versus 4 doses at 6 and 12 months in arm 3 only.

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=4 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in 6MWD From Baseline Change from baseline to 6 months	30.25 Meters Standard Deviation 33.61	—
Change in 6MWD From Baseline Change from baseline to 12 months	7.33 Meters Standard Deviation 9.02	—

SECONDARY outcome

Timeframe: 6 months

Population: Participants in Arm 1 and Arm 2 and 3 combined for whom PVR was measured at baseline and 6 months.

Comparison of change from baseline after 4 doses of study product (Arms 2 and 3 versus Arm 1)

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=5 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months n=7 Participants 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in Pulmonary Vascular Resistance From Baseline	0.444 Wood Units (WU) Standard Deviation 1.18	0.576 Wood Units (WU) Standard Deviation 2.07

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: Participants in Arm 2 and Arm 3 for whom the PVR was measured at baseline and 12 months

Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arm 2 versus Arm 3)

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=3 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months n=4 Participants 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in Pulmonary Vascular Resistance From Baseline	0.09 Wood Units (WU) Standard Deviation 1.81	2.15 Wood Units (WU) Standard Deviation 3.09

SECONDARY outcome

Timeframe: 6 and12 months

Population: All participants in whom the PVR was measurement at baseline, 6, and 12 months.

Incremental effect of 8 versus 4 doses of cell therapy product on PVR at 6 and 12 months (Arm 3 only)

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=4 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Incremental Effect of 8 Versus 4 Doses of Cell Therapy Product on PVR Baseline to 6 months	0.76 Wood Units (WU) Standard Deviation 0.87	—
Incremental Effect of 8 Versus 4 Doses of Cell Therapy Product on PVR Baseline to 12 months	2.15 Wood Units (WU) Standard Deviation 3.09	—

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: All participants in Arm 1 and Arms 2 and 3 combined for whom results of the SF-36 questionnaire were collected baseline and 6 months.

Comparison of change from baseline measured by the Short Form 36 (SF-36) Health Survey after delivery of 4 doses of study product (Arms 2 and 3 versus Arm 1). Scale used ranging from 0-100. Lower scores indicate more significant limitations.

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=5 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months n=7 Participants 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in Quality of Life Measures From Baseline Physical Component	2.78 score on a scale Standard Deviation 5.11	3.2 score on a scale Standard Deviation 10.71
Change in Quality of Life Measures From Baseline Mental Component	-2.60 score on a scale Standard Deviation 11.32	-2.50 score on a scale Standard Deviation 6.93

SECONDARY outcome

Timeframe: 12 months

Population: All participants in Arm 2 and 3 for whom results of the SF-36 questionnaire were collected baseline and 12 months.

Comparison in change from baseline measured by SF-36 Survey after delivery of 4 versus 8 doses of study product (Arm 2 versus Arm 3). Scale used ranging from 0-100. Lower scores indicate more significant limitations.

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo During First 6 Months n=3 Participants 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1	Arm 2 and 3 During First 6 Months n=4 Participants 4 monthly IV injections with EPCs transfected with eNOS during Course 1
Change in Quality of Life Measures From Baseline Physical Component	10.5 Change in Score Standard Deviation 2.78	2.5 Change in Score Standard Deviation 13.86
Change in Quality of Life Measures From Baseline Mental Component	14.3 Change in Score Standard Deviation 21.58	-1.10 Change in Score Standard Deviation 9.10

Adverse Events

Placebo Followed by Autologous EPCs Transfected With eNOS

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Autologous EPCs Transfected With eNOS Followed by Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Autologous EPCs Transfected With eNOS

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Followed by Autologous EPCs Transfected With eNOS n=5 participants at risk 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1 followed by 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 2 Placebo followed by Autologous EPCs transfected with human eNOS: 4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months	Autologous EPCs Transfected With eNOS Followed by Placebo n=3 participants at risk 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 1 followed by 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 2 Autologous EPCs transfected with human eNOS followed by Placebo: 4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months	Autologous EPCs Transfected With eNOS n=4 participants at risk 4 monthly IV injections of Autologous EPCs transfected with human eNOS in Course 1 followed by 4 monthly injections of Autologous EPCs transfected with human eNOS in Course 2 (total of 160 million cells) Autologous EPCs transfected with human eNOS: 4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months
Respiratory, thoracic and mediastinal disorders Pneumonia	20.0% 1/5 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Cardiac disorders Volume Overload	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.

Other adverse events

Additional Information

Duncan Stewart, Clinical Trial Medical Consultant

Northern Therapeutics, Inc.

Phone: 613-737-8899

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first publication or presentation or results is to be made by the study sponsor within 18 months of trial completion. For publications or results communications after that time, Principal Investigators must provide a copy of the proposed manuscript or presentation to the study sponsor for review at least 45 days prior to submission for consideration of publication, and the sponsor may request removal of confidential information which is protected as intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Followed by Autologous EPCs Transfected With eNOS n=5 participants at risk 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1 followed by 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 2 Placebo followed by Autologous EPCs transfected with human eNOS: 4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months	Autologous EPCs Transfected With eNOS Followed by Placebo n=3 participants at risk 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 1 followed by 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 2 Autologous EPCs transfected with human eNOS followed by Placebo: 4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months	Autologous EPCs Transfected With eNOS n=4 participants at risk 4 monthly IV injections of Autologous EPCs transfected with human eNOS in Course 1 followed by 4 monthly injections of Autologous EPCs transfected with human eNOS in Course 2 (total of 160 million cells) Autologous EPCs transfected with human eNOS: 4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months
Respiratory, thoracic and mediastinal disorders Pneumonia	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Eye disorders Swollen Left Eye Lid	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Infection	60.0% 3/5 • Number of events 5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	66.7% 2/3 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.	50.0% 2/4 • Number of events 5 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Blood and lymphatic system disorders Severe Anemia	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Infections and infestations Tonsil Exudate	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Nervous system disorders Loss of Balance	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Gastrointestinal disorders Atrophic Gastritis	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Gastrointestinal disorders Erosive Esophagitis	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Infections and infestations Influenza	40.0% 2/5 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Nervous system disorders Vertigo	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Vascular disorders Nose Bleed	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Infections and infestations COVID-19	40.0% 2/5 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
General disorders Sinusitis	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Infections and infestations Sinus Infection	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Infections and infestations Tooth Infection	20.0% 1/5 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Musculoskeletal and connective tissue disorders Left Ankle Sprain	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Immune system disorders Allergy Symptoms	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Cardiac disorders Elevated Jugular Venous Pulse	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Nervous system disorders Anxiety	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Gastrointestinal disorders Pulsatile Right Upper Quadrant Abdomen	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Cardiac disorders Heart Failure	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
General disorders Right Ankle Edema	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Eye disorders Right Eye Stye	20.0% 1/5 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Eye disorders Eyelid Infection	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Eye disorders Eye Irritation	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Cardiac disorders Increased Pulmonary Vascular Resistance	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Nervous system disorders Dizziness	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	66.7% 2/3 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Gastrointestinal disorders Emesis	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
General disorders Increased Frequency of Headaches	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	33.3% 1/3 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/4 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Endocrine disorders Hypokalemia	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Cardiac disorders Elevated C-Reactive Protein	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	50.0% 2/4 • Number of events 2 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Nervous system disorders Warm feeling	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Nervous system disorders Weakness/Syncope	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Gastrointestinal disorders Abdominal Pain	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Cardiac disorders Volume Overload	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Skin and subcutaneous tissue disorders Right Submandibular Firm Node	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.
Musculoskeletal and connective tissue disorders Left Knee Meniscus Deterioration	0.00% 0/5 • Adverse event data collection took place during the 12-month treatment phase of the trial.	0.00% 0/3 • Adverse event data collection took place during the 12-month treatment phase of the trial.	25.0% 1/4 • Number of events 1 • Adverse event data collection took place during the 12-month treatment phase of the trial.