Trial Outcomes & Findings for Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease (NCT NCT02782741)

NCT ID: NCT02782741

Last Updated: 2024-04-04

Results Overview

FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC \[percent (%) predicted, as continuous\], sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) \* 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 101 participants
• Primary outcome timeframe: Baseline, Week 49
• Results posted on: 2024-04-04

Participant Flow

The study was conducted at 69 centers in 26 countries. A total of 149 participants were screened between 02 November 2016 and 22 March 2019, of which 100 participants were enrolled and randomized (1:1 ratio) to receive avalglucosidase alfa or alglucosidase alfa. A total of 48 participants were screen failure mainly due to meeting exclusion criteria. 1 pediatric participant entered open-label treatment period directly.

Randomization was stratified by baseline percent (%) predicted forced vital capacity (FVC): less than (<) 55% or greater than or equal to (>=) 55%, gender, age (<18 years and >=18 years), and country (Japan or ex-Japan). Data reported based on study completion date, i.e. 31 May 2023.

Participant milestones

Measure	Avalglucosidase Alfa Avalglucosidase alfa 20 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (q2w) up to Week 49 in blinded treatment period (also known as primary analysis period \[PAP\]); followed by same treatment from Week 50 to 289 in an open-label avalglucosidase alfa long-term follow-up phase.	Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 289 in an open-label avalglucosidase alfa long-term follow-up phase.	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
Blinded Treatment Period: up to Week 49 STARTED	51	49	0
Blinded Treatment Period: up to Week 49 Safety Population	51	49	0
Blinded Treatment Period: up to Week 49 COMPLETED	51	44	0
Blinded Treatment Period: up to Week 49 NOT COMPLETED	0	5	0
Open-label Long-term: Week 50 to 289 STARTED	51	44	1
Open-label Long-term: Week 50 to 289 Safety Population	51	44	1
Open-label Long-term: Week 50 to 289 COMPLETED	44	36	1
Open-label Long-term: Week 50 to 289 NOT COMPLETED	7	8	0

Reasons for withdrawal

Measure	Avalglucosidase Alfa Avalglucosidase alfa 20 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (q2w) up to Week 49 in blinded treatment period (also known as primary analysis period \[PAP\]); followed by same treatment from Week 50 to 289 in an open-label avalglucosidase alfa long-term follow-up phase.	Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 289 in an open-label avalglucosidase alfa long-term follow-up phase.	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
Blinded Treatment Period: up to Week 49 Adverse Event	0	4	0
Blinded Treatment Period: up to Week 49 Other	0	1	0
Open-label Long-term: Week 50 to 289 Adverse Event	2	3	0
Open-label Long-term: Week 50 to 289 Poor compliance to protocol	0	1	0
Open-label Long-term: Week 50 to 289 Other	5	4	0

Baseline Characteristics

Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease

Baseline characteristics by cohort

Measure	Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by same treatment from Week 50 to 289 in an open-label avalglucosidase alfa long-term follow-up phase.	Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 289 in an open-label avalglucosidase alfa long-term follow-up phase.	Total n=100 Participants Total of all reporting groups
Age, Continuous	46.0 years STANDARD_DEVIATION 14.5 • n=5 Participants	50.3 years STANDARD_DEVIATION 13.7 • n=7 Participants	48.1 years STANDARD_DEVIATION 14.2 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	25 Participants n=7 Participants	52 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	3 Participants n=5 Participants	0 Participants n=7 Participants	3 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	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	47 Participants n=7 Participants	94 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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
Percent Predicted Forced Vital Capacity (FVC) in Upright Position	62.5 percent predicted FVC STANDARD_DEVIATION 14.4 • n=5 Participants	61.6 percent predicted FVC STANDARD_DEVIATION 12.4 • n=7 Participants	62.1 percent predicted FVC STANDARD_DEVIATION 13.4 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population.

FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC [percent (%) predicted, as continuous], sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) * 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49	2.89 percent predicted FVC Standard Error 0.88	0.46 percent predicted FVC Standard Error 0.93	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population.

6MWT was a standardized test that measured the distance (in meters) covered by the participant by walking on a flat, hard surface in a period of a 6-minute walk. Mean distance walked gives an indication of functional endurance. The greater the distance (that a participant could walk in 6 minutes), the greater the endurance. LS mean and SE were derived from MMRM model with baseline FVC (% predicted) and baseline 6MWT (distance walked in meter), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49	32.21 meters Standard Error 9.93	2.19 meters Standard Error 10.40	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population.

MIP is a quick and non-invasive test to measure strength of inspiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MIP refers to how much air pressure force an individual creates by inhaling through the mouth as hard as possible. LS mean and SE were derived from MMRM model for MIP % predicted adjusted for MIP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49	0.17 percent predicted MIP Standard Error 3.60	-2.96 percent predicted MIP Standard Error 3.79	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population.

MEP is a quick and non-invasive test to measure strength of expiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MEP is the greater pressure generated during maximal expiration. LS mean and SE were derived from MMRM model for MEP % predicted adjusted for MEP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49	3.02 percent predicted MEP Standard Error 3.87	4.95 percent predicted MEP Standard Error 4.07	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population.

HHD: a portable method for strength quantitation. To complete a make test, participant exerted maximal force against dynamometer with gradual increase in force and completed isometric hold for 4-5 seconds. Muscle strengths were collected in Newton. Every muscle group (hip: flexion, extension, abduction; knee: flexion, extension and ankle dorsiflexion) were measured 2 times and highest value was reported. Summary score was sum of 12 measurements (2 measurements per muscle group) from 6 muscle groups on each side (left and right). An increase from Baseline was reflective of increased muscle strength, whereas a decrease from Baseline was reflective of decreased muscle strength. LS mean and SE were derived from MMRM model for HHD lower extremity muscle strength composite score adjusted for summary HHD lower extremity score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-Held Dynamometry (HHD)	260.69 Newton Standard Error 46.07	153.72 Newton Standard Error 48.54	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population.

The QMFT was an observer administered test to evaluate changes in motor function. QMFT comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored separately on a 5-point ordinal scale (ranged from 0 to 4, higher score indicated better outcome). Total QMFT score was obtained by adding the scores of all items and ranged from 0 (unable to perform motor function tests) to 64 (normal muscle function), higher score represented better outcome. LS mean and SE were derived from MMRM models adjusted for total QMFT score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49	3.98 scores on a scale Standard Error 0.63	1.89 scores on a scale Standard Error 0.69	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

SF-12, a 12 item-questionnaire, used to assess health-related quality of life in participants aged >=18 years at screening/baseline. SF-12 consisted of 12 items, which were categorized into eight domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health), higher scores indicated good health condition. These eight domains were further summarized into 2 summary scores, PCS and MCS. The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), higher scores indicated a better health-related quality of life. LS mean and SE were derived from MMRM models adjusted for baseline score (PCS or MCS), baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=50 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Change From Baseline in 12-Item Short-Form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49 MCS score	2.88 scores on a scale Standard Error 1.22	0.76 scores on a scale Standard Error 1.32	—
PAP: Change From Baseline in 12-Item Short-Form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49 PCS score	2.37 scores on a scale Standard Error 0.99	1.60 scores on a scale Standard Error 1.07	—

SECONDARY outcome

Timeframe: From Baseline up to Week 49

Population: Analysis was performed on safety population which included participants who had received at least 1 infusion (partial or total) and were analyzed according to the treatment received.

AE: any untoward medical occurrence in participant who took study drug and not necessarily have to had causal relationship with treatment. TEAEs: AEs that developed/worsened in grade/became serious during TEAE period in PAP (from time of 1st treatment date to last treatment date+4 weeks for participants who didn't receive any treatment in open-label or to time just prior to 1st treatment in open-label for participants who received treatment in open-label). Protocol-defined IARs: AE of special interest (AESIs) that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion + 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date + 1 day and it was related to study drug.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Infusion-Associated Reactions (IARs) Any TEAE	44 Participants	45 Participants	—
PAP: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Infusion-Associated Reactions (IARs) Any Protocol-defined IARs	13 Participants	16 Participants	—
PAP: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Infusion-Associated Reactions (IARs) Any Algorithm-defined IARs	15 Participants	20 Participants	—

SECONDARY outcome

Timeframe: Week 50 to 289 in open-label long-term period

Population: Analysis was performed on safety population.

AE: any untoward medical occurrence in a participant who received study drug and did not necessarily have to had a causal relationship with treatment. TEAEs in open-label: AEs that developed/worsened in grade/became serious during TEAE period in open-label (from time of 1st open-label treatment to last treatment date + 4 weeks). Protocol-defined IARs: defined as AESIs that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion plus 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date plus 1 day and it was related to study drug.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=44 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only n=1 Participants One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
Open-label Period: Number of Participants With TEAEs and IARs Any TEAE	51 Participants	43 Participants	1 Participants
Open-label Period: Number of Participants With TEAEs and IARs Any Protocol-defined IARs	12 Participants	22 Participants	0 Participants
Open-label Period: Number of Participants With TEAEs and IARs Any Algorithm-defined IARs	16 Participants	24 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline up to Week 49

Population: Analysis was performed on ADA evaluable population which consisted of participants who had received at least 1 infusion (partial or total) and had at least one ADA sample taken post-baseline after drug administration that was appropriate for ADA testing with a reportable result.

ADA response categories: 1) Treatment-induced: ADAs developed following administration of the study drug. If the baseline ADA sample was missing or non-reportable and at least one reportable on-treatment ADA sample was available, the baseline sample was considered as "negative". 2) Treatment-boosted: Pre-existing ADAs that were boosted at least two titer steps from baseline (i.e., 4 fold increase in titers) following administration of the study drug (any time after the first drug administration). 3) Treatment emergent: combination of treatment induced and treatment boosted.

Outcome measures

Measure	PAP: Avalglucosidase Alfa n=51 Participants Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=48 Participants Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Avalglucosidase Alfa in Open-label Only One participant included directly in the open-label long-term period (Week 50 to 289) and received avalglucosidase alfa 20 mg/kg IV infusion q2w throughout the treatment period.
PAP: Percentage of Participants With Treatment-Emergent Antidrug Antibodies (ADA) Response Treatment-Induced	95.9 percentage of participants	95.7 percentage of participants	—
PAP: Percentage of Participants With Treatment-Emergent Antidrug Antibodies (ADA) Response Treatment-boosted ADA	100 percentage of participants	100 percentage of participants	—
PAP: Percentage of Participants With Treatment-Emergent Antidrug Antibodies (ADA) Response Treatment emergent ADA	96.1 percentage of participants	95.8 percentage of participants	—

Adverse Events

PAP: Avalglucosidase Alfa

Serious events: 8 serious events

Other events: 40 other events

Deaths: 0 deaths

PAP: Alglucosidase Alfa

Serious events: 12 serious events

Other events: 44 other events

Deaths: 1 deaths

Open-label: Avalglucosidase Alfa

Serious events: 14 serious events

Other events: 50 other events

Deaths: 0 deaths

Open-label: Alglucosidase Alfa-PAP Then Avalglucosidase Alfa

Serious events: 14 serious events

Other events: 40 other events

Deaths: 2 deaths

Serious adverse events

Measure	PAP: Avalglucosidase Alfa n=51 participants at risk Avalglucosidase alfa 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 participants at risk Alglucosidase alfa 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Open-label: Avalglucosidase Alfa n=52 participants at risk Included all subjects who received avalglucosidase alfa, 20 mg/kg IV infusion q2w from Week 50 up to 289 based on product approval status in an open-label avalglucosidase alfa long-term follow-up phase.	Open-label: Alglucosidase Alfa-PAP Then Avalglucosidase Alfa n=44 participants at risk Included all subjects who received avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 up to 289 based on product approval status in an open-label avalglucosidase alfa long-term follow-up phase.
Vascular disorders Hypertensive Crisis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Vascular disorders Hypotension	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Bacteraemia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Covid-19	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Covid-19 Pneumonia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Device Related Infection	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Pneumonia	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Sepsis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Urinary Tract Infection	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma Pancreas	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Oncocytoma	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Endocrine disorders Inappropriate Antidiuretic Hormone Secretion	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Psychiatric disorders Bipolar Disorder	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Brain Stem Stroke	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Cerebellar Ischaemia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Depressed Level Of Consciousness	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Dizziness	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Headache	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Moyamoya Disease	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Subarachnoid Haemorrhage	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Syncope	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Eye disorders Visual Impairment	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Ear and labyrinth disorders Vertigo	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Cardiac disorders Angina Pectoris	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Cardiac disorders Supraventricular Tachycardia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Diaphragmatic Paralysis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Hypoventilation	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Acidosis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	2.0% 1/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Nausea	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Tongue Oedema	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Hepatobiliary disorders Cholecystitis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Hepatobiliary disorders Cholelithiasis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Cold Sweat	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Skin Discolouration	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Renal and urinary disorders Calculus Urinary	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Renal and urinary disorders Hydronephrosis	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Renal and urinary disorders Nephrolithiasis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Renal and urinary disorders Pelvi-Ureteric Obstruction	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Renal and urinary disorders Renal Colic	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Reproductive system and breast disorders Breast Cyst	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Congenital, familial and genetic disorders Glycogen Storage Disease Type Ii	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Chills	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Blood Pressure Increased	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Body Temperature Increased	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Haemoglobin Decreased	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Heart Rate Increased	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Oxygen Saturation Decreased	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Viiith Nerve Injury	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Wound Dehiscence	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.

Other adverse events

Measure	PAP: Avalglucosidase Alfa n=51 participants at risk Avalglucosidase alfa 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	PAP: Alglucosidase Alfa n=49 participants at risk Alglucosidase alfa 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Open-label: Avalglucosidase Alfa n=52 participants at risk Included all subjects who received avalglucosidase alfa, 20 mg/kg IV infusion q2w from Week 50 up to 289 based on product approval status in an open-label avalglucosidase alfa long-term follow-up phase.	Open-label: Alglucosidase Alfa-PAP Then Avalglucosidase Alfa n=44 participants at risk Included all subjects who received avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 up to 289 based on product approval status in an open-label avalglucosidase alfa long-term follow-up phase.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Bronchitis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Covid-19	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	30.8% 16/52 • Number of events 17 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	20.5% 9/44 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Cystitis	5.9% 3/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Influenza	19.6% 10/51 • Number of events 11 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	7.7% 4/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Nasopharyngitis	23.5% 12/51 • Number of events 15 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	24.5% 12/49 • Number of events 17 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	28.8% 15/52 • Number of events 23 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	29.5% 13/44 • Number of events 27 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Pneumonia	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Sinusitis	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Upper Respiratory Tract Infection	7.8% 4/51 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	18.2% 8/44 • Number of events 10 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Infections and infestations Urinary Tract Infection	3.9% 2/51 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	15.4% 8/52 • Number of events 10 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Immune system disorders Seasonal Allergy	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Metabolism and nutrition disorders Gout	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Metabolism and nutrition disorders Vitamin D Deficiency	3.9% 2/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.6% 5/52 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Psychiatric disorders Depression	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Psychiatric disorders Insomnia	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Dizziness	9.8% 5/51 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 14 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.5% 6/52 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Headache	21.6% 11/51 • Number of events 32 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	32.7% 16/49 • Number of events 102 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	23.1% 12/52 • Number of events 42 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	38.6% 17/44 • Number of events 220 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Paraesthesia	5.9% 3/51 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Syncope	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Nervous system disorders Tremor	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 12 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Eye disorders Conjunctival Haemorrhage	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Eye disorders Ocular Hyperaemia	2.0% 1/51 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Ear and labyrinth disorders Vertigo	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Vascular disorders Flushing	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Vascular disorders Hypertension	2.0% 1/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	13.5% 7/52 • Number of events 21 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Cough	3.9% 2/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	8.2% 4/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	7.7% 4/52 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.9% 2/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	10.2% 5/49 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	3.9% 2/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	10.2% 5/49 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Abdominal Pain	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.6% 5/52 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Abdominal Pain Upper	3.9% 2/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Diarrhoea	11.8% 6/51 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	16.3% 8/49 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	13.5% 7/52 • Number of events 15 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	31.8% 14/44 • Number of events 19 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Dyspepsia	5.9% 3/51 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Nausea	11.8% 6/51 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	14.3% 7/49 • Number of events 15 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	23.1% 12/52 • Number of events 16 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	15.9% 7/44 • Number of events 22 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Toothache	2.0% 1/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Gastrointestinal disorders Vomiting	7.8% 4/51 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	13.6% 6/44 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Erythema	5.9% 3/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Pruritus	7.8% 4/51 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	8.2% 4/49 • Number of events 11 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	25.0% 11/44 • Number of events 51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Rash	3.9% 2/51 • Number of events 11 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	8.2% 4/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	7.7% 4/52 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	18.2% 8/44 • Number of events 16 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Skin and subcutaneous tissue disorders Urticaria	5.9% 3/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.6% 5/52 • Number of events 12 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Arthralgia	11.8% 6/51 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	16.3% 8/49 • Number of events 11 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	25.0% 13/52 • Number of events 27 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	29.5% 13/44 • Number of events 29 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Back Pain	23.5% 12/51 • Number of events 15 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	10.2% 5/49 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	21.2% 11/52 • Number of events 13 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	22.7% 10/44 • Number of events 20 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Muscle Spasms	5.9% 3/51 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	8.2% 4/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	7.7% 4/52 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 117 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Musculoskeletal Stiffness	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Myalgia	9.8% 5/51 • Number of events 15 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	14.3% 7/49 • Number of events 12 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.5% 6/52 • Number of events 12 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	22.7% 10/44 • Number of events 22 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Musculoskeletal and connective tissue disorders Pain In Extremity	15.7% 8/51 • Number of events 9 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	16.3% 8/49 • Number of events 15 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	19.2% 10/52 • Number of events 29 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	20.5% 9/44 • Number of events 19 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Renal and urinary disorders Dysuria	3.9% 2/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Chest Discomfort	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Chills	2.0% 1/51 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.1% 2/49 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	7.7% 4/52 • Number of events 13 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 13 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Fatigue	17.6% 9/51 • Number of events 11 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	14.3% 7/49 • Number of events 27 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	7.7% 4/52 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	20.5% 9/44 • Number of events 75 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Influenza Like Illness	3.9% 2/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.3% 1/44 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Infusion Site Extravasation	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	3.8% 2/52 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 8 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Oedema Peripheral	5.9% 3/51 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.6% 5/52 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.1% 4/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Pain	3.9% 2/51 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	10.2% 5/49 • Number of events 13 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	13.6% 6/44 • Number of events 14 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Peripheral Swelling	2.0% 1/51 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	11.4% 5/44 • Number of events 6 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
General disorders Pyrexia	3.9% 2/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	8.2% 4/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	15.4% 8/52 • Number of events 10 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	13.6% 6/44 • Number of events 11 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Alanine Aminotransferase Increased	3.9% 2/51 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.1% 3/49 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	4.5% 2/44 • Number of events 2 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Investigations Blood Pressure Increased	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Arthropod Bite	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	1.9% 1/52 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Contusion	9.8% 5/51 • Number of events 5 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	8.2% 4/49 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	9.6% 5/52 • Number of events 7 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 4 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Fall	13.7% 7/51 • Number of events 12 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	20.4% 10/49 • Number of events 13 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	19.2% 10/52 • Number of events 28 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	18.2% 8/44 • Number of events 21 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Joint Injury	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/49 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	5.8% 3/52 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/44 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.
Injury, poisoning and procedural complications Post-Traumatic Pain	0.00% 0/51 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	2.0% 1/49 • Number of events 1 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	0.00% 0/52 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.	6.8% 3/44 • Number of events 3 • Up to Week 49 in PAP and from Week 50 to 289 in open-label long-term period AEs and deaths: TEAEs that developed/worsened in grade/became serious during 'TEAE period' (PAP: from first treatment date to last treatment date+4 weeks for participants not exposed to treatment in open-label or to time just prior to first dose in open-label for those exposed to open-label \[time from first study drug to last dose+4 weeks\]). Safety population.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
• Publication restrictions are in place

Restriction type: OTHER