Trial Outcomes & Findings for Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD) (NCT NCT04371666)

Last Updated: 2024-03-12

Results Overview

The PUL module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the 3 subscales. Analysis was done using a random coefficient model (RCM), which included fixed effects of time (as a continuous variable), treatment, and treatment-by-time interaction, with baseline ordinal PUL entry score as covariate.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

98 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2024-03-12

Participant Flow

The study included 2 periods: Double-blind (DB) Treatment Period and Open-label Extension (OLE) Period.

Participant milestones

Participant milestones
Measure	Pamrevlumab Participants received pamrevlumab intravenously (IV) every 2 weeks for up to 52 weeks in the DB treatment period. After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.	Placebo Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period. After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.
DB Treatment Period (52 Weeks) STARTED	49	49
DB Treatment Period (52 Weeks) Received at Least 1 Dose of Study Drug	48	49
DB Treatment Period (52 Weeks) COMPLETED	44	46
DB Treatment Period (52 Weeks) NOT COMPLETED	5	3
OLE (Maximum Exposure: 93.4 Weeks) STARTED	43	43
OLE (Maximum Exposure: 93.4 Weeks) Received at Least 1 Dose of Study Drug	43	43
OLE (Maximum Exposure: 93.4 Weeks) COMPLETED	0	0
OLE (Maximum Exposure: 93.4 Weeks) NOT COMPLETED	43	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Pamrevlumab Participants received pamrevlumab intravenously (IV) every 2 weeks for up to 52 weeks in the DB treatment period. After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.	Placebo Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period. After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.
DB Treatment Period (52 Weeks) Adverse Event	3	1
DB Treatment Period (52 Weeks) Participant/Legal Guardian Decision	1	2
DB Treatment Period (52 Weeks) Other than specified	1	0
OLE (Maximum Exposure: 93.4 Weeks) Participant/Legal Guardian Decision	2	2
OLE (Maximum Exposure: 93.4 Weeks) Sponsor Decision to Terminate Study	40	41
OLE (Maximum Exposure: 93.4 Weeks) Other than specified	1	0

Baseline Characteristics

Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pamrevlumab n=49 Participants Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period. After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.	Placebo n=49 Participants Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period. After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.	Total n=98 Participants Total of all reporting groups
Age, Continuous	15.6 years STANDARD_DEVIATION 2.74 • n=5 Participants	15.5 years STANDARD_DEVIATION 2.42 • n=7 Participants	15.5 years STANDARD_DEVIATION 2.57 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	49 Participants n=7 Participants	98 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	41 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	35 Participants n=7 Participants	77 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: The modified intent-to-treat (mITT) population included all randomized participants with a PUL Entry score ≥2 (excluding PUL entry scores of 1) at baseline. Here, 'Overall number of participants analyzed' = participants evaluable for specified outcome measure.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=38 Participants Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	Placebo n=40 Participants Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.
Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52	-2.036 units on a scale Standard Error 0.4471	-2.119 units on a scale Standard Error 0.3367

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: The mITT population included all randomized participants with a PUL Entry score ≥2 (excluding PUL entry scores of 1) at baseline. Here, 'Overall number of participants analyzed' = participants evaluable for specified outcome measure.

FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) \* 100%. Analysis was done using an RCM, which included fixed effects of time (as a continuous variable), treatment, and treatment-by-time interaction, with baseline value as covariate.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=38 Participants Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	Placebo n=40 Participants Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.
Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry	-8.349 percentage of predicted FVC Standard Error 1.5760	-5.989 percentage of predicted FVC Standard Error 1.2233

SECONDARY outcome

Timeframe: Baseline, Week 52

The HHM was used to measure distal upper arm strength (grip strength). Data has been presented by dominant and non-dominant hand. Grip Strength was analyzed using a MMRM with fixed effects for treatment, visit (as a factor), treatment-by-visit interaction, and covariates (baseline values).

Outcome measures

Outcome measures
Measure	Pamrevlumab n=37 Participants Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	Placebo n=39 Participants Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.
Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM) Grip Strength by Dominant Hand	-7.570 newton Standard Error 2.0989	-0.072 newton Standard Error 2.2065
Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM) Grip Strength by Nondominant Hand	-7.627 newton Standard Error 1.8893	-0.012 newton Standard Error 1.8546

SECONDARY outcome

Timeframe: Baseline, Week 52

LVEF% is an important measure of cardiac function. LVEF is a fraction of blood (in percent) pumped out of the left ventricle of the heart (the main pumping chamber). The LVEF% was analyzed using an analysis of covariance (ANCOVA) model with treatment and baseline value.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=33 Participants Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	Placebo n=37 Participants Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.
Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI)	-0.499 percentage of LVEF Standard Error 0.9750	-1.114 percentage of LVEF Standard Error 0.9204

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: The ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for specified outcome measure.

The ppPEF is a measure of the maximal or peak flow produced during an exhalation with maximal effort and, as such, is the most effort-dependent measure of lung function. The ppFEV1 was analyzed using an RCM including fixed effects of time, treatment, and treatment-by-time interaction, with baseline as covariate.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=46 Participants Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	Placebo n=47 Participants Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.
Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry	-4.921 percentage of predicted PEF Standard Error 2.3086	-4.516 percentage of predicted PEF Standard Error 1.7663

Adverse Events

DB Period: Pamrevlumab

Serious events: 8 serious events

Other events: 42 other events

Deaths: 1 deaths

DB Period: Placebo

Serious events: 6 serious events

Other events: 44 other events

Deaths: 0 deaths

OLE Period: Pamrevlumab

Serious events: 5 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Information Desk

FibroGen, Inc.

Phone: 415-978-1441

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).
Publication restrictions are in place

Restriction type: OTHER

Measure	DB Period: Pamrevlumab n=48 participants at risk Participants received pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	DB Period: Placebo n=49 participants at risk Participants received placebo matched to pamrevlumab IV every 2 weeks for up to 52 weeks in the DB treatment period.	OLE Period: Pamrevlumab n=86 participants at risk After completing Week 52 of the DB treatment period, participants in the OLE period then moved to Week 2 of the OLE period and received pamrevlumab IV every 2 weeks.
Cardiac disorders Myocarditis	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	2.0% 1/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Cardiac disorders Cardiac arrest	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Immune system disorders Drug hypersensitivity	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Immune system disorders Food allergy	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Infections and infestations Pneumonia	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	2.0% 1/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	1.2% 1/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Infections and infestations COVID-19	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	2.0% 1/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Infections and infestations Upper respiratory tract infection	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	2.0% 1/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Injury, poisoning and procedural complications Femur fracture	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	6.1% 3/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	2.3% 2/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Injury, poisoning and procedural complications Fracture	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Injury, poisoning and procedural complications Tibia fracture	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Nervous system disorders Loss of consciousness	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Reproductive system and breast disorders Testicular necrosis	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Reproductive system and breast disorders Testicular torsion	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	2.0% 1/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.1% 1/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Gastrointestinal disorders Vomiting	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	1.2% 1/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Infections and infestations Skin infection	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	1.2% 1/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	1.2% 1/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/48 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	0.00% 0/49 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.	1.2% 1/86 • DB treatment period: From first dose of study drug up to 61 weeks OLE period: From first dose of study drug up to study termination by Sponsor and safety follow-up (up to approximately 102 weeks) The safety analysis set included all participants who received any dose of study medication.