Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03039686
• Collaborator: (none)
• Enrollment: 166
• Locations: 44
• Arms: 3
• Actual Duration (Months): 33.7
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of two different weekly doses of RO7239361 in ambulatory boys with Duchenne Muscular Dystrophy (DMD).

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: RO7239361; Drug: Placebo for RO7239361	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 166 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy
• Actual Study Start Date: Jul 6, 2017
• Actual Primary Completion Date: Apr 28, 2020
• Actual Study Completion Date: Apr 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RO7239361 Low Dose Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Drug: RO7239361; Take RO7239361 subcutaneously on specified days over a 48 week blinded period
Experimental: RO7239361 High Dose Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Drug: RO7239361; Take RO7239361 subcutaneously on specified days over a 48 week blinded period
Placebo Comparator: Placebo Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Drug: Placebo for RO7239361; Take placebo subcutaneously on specified days over a 48 week blinded period

Outcome Measures

Primary Outcome Measures

1. Baseline for the North Star Ambulatory Assessment (NSAA) Total Score [Baseline]

   The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance.

2. Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 [Baseline, Week 48]

   The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).

Secondary Outcome Measures

1. Baseline Time for 4 Stair Climb [Baseline]

   The time to complete the 4 stair climb was measured at baseline.

2. Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) [Baseline, Week 48]

   4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).

3. Baseline for the Time to Stand From Supine [Baseline]

   The time required for a participant to stand from supine position. A longer time reflects a worse outcome.

4. Change From Baseline at Week 48 in Stand From Supine Velocity [Baseline, Week 48]

   The time required for a participant to stand from supine position. A longer time reflects a worse outcome. A negative change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).

5. Baseline Time for 10 Meter Walk/Run [Baseline]

   The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome.

6. Change From Baseline at Week 48 in 10 M Walk/Run Velocity [Baseline, Week 48]

   The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).

7. Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale [Baseline]

   The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance.

8. Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale [Baseline, Week 48]

   The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).

9. Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength [Baseline, Week 48]

   Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement.

10. Baseline for the 6 Minute Walk Distance (6MWD) [Baseline]

    The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome.

11. Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) [Baseline, Week 48]

    The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).

12. Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 [Baseline, Week 48]

    The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse" at Week 48 as compared to baseline.

13. Change From Baseline at Week 48 in 95th Percentile Stride Velocity [Baseline, Week 48]

    Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement.

14. Number of Participants With Adverse Events (AEs) [During DB period (48 weeks) and Whole study (up to approximately 34 months)]

    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

15. Number of Participants With AEs Leading to Discontinuation [During DB period (48 weeks) and Whole study (up to approximately 34 months)]

    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with DMD by confirmed medical history and genetic testing

• Able to walk without assistance

• Minimum North Star Ambulatory Assessment score of 15 at screening

• Able to walk up 4 stairs in 8 seconds or less

• Weigh at least 15 kg (33 lbs)

• Taking corticosteroids for DMD

Exclusion Criteria:

• Any behavior or mental issue that will affect the ability to complete the required study procedures

• Previously or currently taking medications like androgens or human growth hormone

• Use of a ventilator during the day

• Unable to have blood samples collected or receive an injection under the skin

• Concomitant or previous participation at any time in a gene therapy study

Other protocol defined Inclusion/Exclusion Criteria could apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neuromuscular Research Center	Phoenix	Arizona	United States	85028
2	Stanford University	Palo Alto	California	United States	94304
3	University of California Davis Medical Center	Sacramento	California	United States	95817
4	Yale University School of Medicine ; Pulmonary & Critical Care	New Haven	Connecticut	United States	06510
5	University of Florida	Gainesville	Florida	United States	32607
6	Nemours Children's Hospital	Orlando	Florida	United States	32827
7	Rare Disease Research, LLC	Atlanta	Georgia	United States	30318
8	Rush University Medical Center - PPDS	Chicago	Illinois	United States	60612
9	University of Iowa	Iowa City	Iowa	United States	52242
10	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
11	Kennedy Krieger Institute	Baltimore	Maryland	United States	21205
12	University of Massachusetts Memorial Childrens Medical Center; Department of Neurology	Worcester	Massachusetts	United States	01655
13	Saint Louis Children's Hospital	Saint Louis	Missouri	United States	63110
14	Las Vegas Clinic	Las Vegas	Nevada	United States	89145
15	Cincinnati Childrens Hospital Medical Center;Investigational Pharmacy	Cincinnati	Ohio	United States	45229
16	Nationwide Childrens Hospital; Research Institute at Nationwide Childrens Hospital	Columbus	Ohio	United States	43205
17	Seattle Children's Hospital	Seattle	Washington	United States	98105
18	Instituto centenario	Buenos Aires		Argentina	C1204AAD
19	Children's Hospital Westmead; Paediatrics & Child Health	Westmead	New South Wales	Australia	2145
20	Lady Cilento Children's Hospital; Neurosciences Department	South Brisbane	Queensland	Australia	4101
21	Royal Children's Hospital	Parkville	Victoria	Australia	3052
22	UZ Gent	Gent		Belgium	9000
23	London Health Sciences Centre; Children's Hospital; Pediatrics	London	Ontario	Canada	N6A 5W9
24	Children'S Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
25	Hospices Civils de Lyon	Lyon		France	69004
26	Hotel Dieu; Service Pharmacie Essais Cliniques	Nantes		France	44093
27	Hopital Armand Trousseau; centre reference Maladies Neuro-musculaires Est parisien Neuropediatrie	Paris Cedex 12		France	75571
28	Hopitaux Universitaires de Strasbourg	Strasbourg		France	67091
29	Universitatsklinikum Essen; Innere Klinik	Essen		Germany	45122
30	Fondazione Serena Onlus - CENTRO CLINICO NEMO	Milano	Emilia-Romagna	Italy	20162
31	Fondazione Policlinico Universitario A Gemelli; Servizio di Farmacia	Rome	Lazio	Italy	00168
32	Az. Osp. Universitaria Pol. G. Martino; Dip. Neuroscienze, Scienze Psichiatriche e Anest.	Messina	Sicilia	Italy	98125
33	Hyogo College of Medicine Hospital	Hyogo		Japan	663-8501
34	Miyagi Children's Hospital	Miyagi		Japan	989-3126
35	Shinshu University Hospital	Nagano		Japan	390-8621
36	National Hospital Organization Osaka Toneyama Medical Center	Osaka		Japan	560-8552
37	National Center of Neurology and Psychiatry	Tokyo		Japan	187-8551
38	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZA
39	Radboud University Nijmegen Medical Centre; Ophthalmology	Nijmegen		Netherlands	6525 EX
40	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona	Spain	08950
41	Hospital Universitari i Politecnic La Fe de Valencia; Servicio de Farmacia	Valencia		Spain	46026
42	Drottning Silvias Barn- och ungdomssjukhus; Kliniken for barnmedicin	Goeteborg		Sweden	41685
43	Alder Hey Children s Hospital; Department of Pediatrics	Liverpool		United Kingdom	L12 2AP
44	UCL Institute of Child Health & Great Ormond Street Hospital for Children	London		United Kingdom	WC1N 1EH

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Aug 16, 2018
• Statistical Analysis Plan - Oct 11, 2019

More Information

Additional Information:

• FDA Safety Alerts and Recalls
• Provides information about the Roche clinical trial NCT03039686 and molecule being investigated in Duchenne

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03039686
• Other Study ID Numbers: CN001-016; 2016-001654-18; WN40227
• First Posted: Feb 1, 2017
• Last Update Posted: Dec 21, 2020
• Last Verified: Nov 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Hoffmann-La Roche: muscular dystrophy; Duchenne's Muscular Dystrophy; DMD
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Period Title: Double-blind Period
STARTED	56	55	55
COMPLETED	29	26	32
NOT COMPLETED	27	29	23
Period Title: Double-blind Period
STARTED	0	38	42
Completed DB, Did Not Start OL	2	2	3
COMPLETED	0	0	0
NOT COMPLETED	0	38	42

Baseline Characteristics

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose	Total
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Total of all reporting groups
Overall Participants	56	55	55	166
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.4 (1.7)	8.5 (1.8)	8.4 (1.5)	8.5 (1.7)
Age, Customized (participants) [Number]
Children (6-11 years)	56 100%	55 100%	55 100%	166 100%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	56 100%	55 100%	55 100%	166 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 12.5%	5 9.1%	6 10.9%	18 10.8%
Not Hispanic or Latino	43 76.8%	41 74.5%	43 78.2%	127 76.5%
Unknown or Not Reported	6 10.7%	9 16.4%	6 10.9%	21 12.7%
Race/Ethnicity, Customized (participants) [Number]
Asian	9 16.1%	7 12.7%	7 12.7%	23 13.9%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	1 1.8%	1 0.6%
White	42 75%	45 81.8%	45 81.8%	132 79.5%
Other	5 8.9%	3 5.5%	2 3.6%	10 6%

Outcome Measures

1. Primary Outcome

Title	Baseline for the North Star Ambulatory Assessment (NSAA) Total Score
Description	The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Mean (Standard Deviation) [score on a scale]	23.1 (6.4)	24.5 (5.5)	22.7 (6.7)

2. Primary Outcome

Title	Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48
Description	The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=33.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Least Squares Mean (Standard Error) [score on a scale]	-2.99 (0.65)	-3.44 (0.67)	-2.41 (0.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 Low Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -2.17 to 1.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.87
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 High Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; -1.10 to 2.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

3. Secondary Outcome

Title	Baseline Time for 4 Stair Climb
Description	The time to complete the 4 stair climb was measured at baseline.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Mean (Standard Deviation) [seconds (secs)]	3.81 (1.55)	3.85 (1.61)	3.92 (1.91)

4. Secondary Outcome

Title	Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV)
Description	4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=33.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Least Squares Mean (Standard Error) [stairs/sec]	-0.15 (0.07)	-0.15 (0.07)	-0.07 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 Low Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 High Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

5. Secondary Outcome

Title	Baseline for the Time to Stand From Supine
Description	The time required for a participant to stand from supine position. A longer time reflects a worse outcome.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Mean (Standard Deviation) [secs]	6.28 (4.75)	6.15 (4.07)	7.24 (9.22)

6. Secondary Outcome

Title	Change From Baseline at Week 48 in Stand From Supine Velocity
Description	The time required for a participant to stand from supine position. A longer time reflects a worse outcome. A negative change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=28, Low Dose n=28, High Dose n=32.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Least Squares Mean (Standard Error) [1/sec]	-0.05 (0.01)	-0.02 (0.01)	-0.02 (0.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 Low Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 High Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

7. Secondary Outcome

Title	Baseline Time for 10 Meter Walk/Run
Description	The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Mean (Standard Deviation) [secs]	5.38 (1.48)	5.51 (1.68)	5.68 (2.30)

8. Secondary Outcome

Title	Change From Baseline at Week 48 in 10 M Walk/Run Velocity
Description	The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=31.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Least Squares Mean (Standard Error) [m/sec]	-0.23 (0.06)	-0.14 (0.07)	-0.23 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 Low Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 High Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

9. Secondary Outcome

Title	Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale
Description	The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Mean (Standard Deviation) [score on a scale]	85.59 (10.21)	86.54 (9.52)	84.47 (14.76)

10. Secondary Outcome

Title	Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale
Description	The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=31, Low Dose n=29, High Dose n=34.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Least Squares Mean (Standard Error) [score on a scale]	-5.47 (1.79)	-7.47 (1.83)	-4.51 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 Low Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -6.76 to 2.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.41
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 High Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; -3.71 to 5.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.36
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

11. Secondary Outcome

Title	Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength
Description	Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Baseline: Knee Extenders	5.58 (2.87)	6.25 (3.63)	5.76 (3.53)
Change from Baseline at Week 48: Knee Extenders	-1.19 (2.13)	-0.47 (2.43)	-0.88 (2.97)
Baseline: Knee Flexors	5.04 (2.58)	5.70 (3.08)	5.04 (2.72)
Change from Baseline at Week 48: Knee Flexors	0.15 (2.24)	0.08 (2.53)	-0.13 (2.29)

12. Secondary Outcome

Title	Baseline for the 6 Minute Walk Distance (6MWD)
Description	The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Mean (Standard Deviation) [meters (m)]	388.33 (69.59)	399.73 (68.35)	370.73 (93.35)

13. Secondary Outcome

Title	Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD)
Description	The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=29, Low Dose n=25, High Dose n=31.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55
Least Squares Mean (Standard Error) [meters (m)]	-41.3 (8.7)	-39.6 (9.0)	-30.0 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 Low Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -21.1 to 24.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.5
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO7239361 High Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.3
	Confidence Interval	(2-Sided) 95%; -11.0 to 33.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.3
	Estimation Comments	Based on the MMRM using an unstructured covariance matrix - change = Baseline + Age IXRS Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.

14. Secondary Outcome

Title	Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48
Description	The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse" at Week 48 as compared to baseline.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. Included in the analysis are only those subjects for whom an efficacy assessment was completed at Week 48.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	36	37	31
Very much improved	0 0%	0 0%	0 0%
Much improved	5.6 10%	2.7 4.9%	3.2 5.8%
Minimally improved	13.9 24.8%	13.5 24.5%	19.4 35.3%
No change	58.3 104.1%	54.1 98.4%	51.6 93.8%
Minimally worse	16.7 29.8%	18.9 34.4%	22.6 41.1%
Much worse	5.6 10%	10.8 19.6%	3.2 5.8%
Very much worse	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Change From Baseline at Week 48 in 95th Percentile Stride Velocity
Description	Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.

Arm/Group Title	Placebo	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	17	19	15
Baseline	1.69 (0.33)	1.54 (0.35)	1.57 (0.46)
Change from Baseline at Week 48	-0.25 (0.39)	-0.22 (0.22)	-0.28 (0.29)

16. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	During DB period (48 weeks) and Whole study (up to approximately 34 months)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study therapy. Data are presented for the arms in the DB period as well as for all RO7239361-treated participants in the whole study.

Arm/Group Title	Placebo DB	RO7239361 Low Dose DB	RO7239361 High Dose DB	RO7239361 Low Dose	RO7239361 High Dose Whole Study
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55	69	68
Double-Blind Period	46 82.1%	48 87.3%	49 89.1%
Whole Study	57 101.8%	56 101.8%

17. Secondary Outcome

Title	Number of Participants With AEs Leading to Discontinuation
Description	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation.
Time Frame	During DB period (48 weeks) and Whole study (up to approximately 34 months)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study therapy. Data are presented for the arms in the DB period as well as for all RO7239361-treated participants in the whole study.

Arm/Group Title	Placebo DB	RO7239361 Low Dose DB	RO7239361 High Dose DB	RO7239361 Low Dose	RO7239361 High Dose
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period.	Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.	Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
Measure Participants	56	55	55	69	68
Double-Blind Period	0 0%	0 0%	0 0%
Whole Study	0 0%	0 0%

Adverse Events

Time Frame	Up to approximately 34 months
Adverse Event Reporting Description	Safety population included all enrolled participants who received at least 1 dose of study therapy.
Arm/Group Title	Placebo DB		RO7239361 Low Dose DB		RO7239361 High Dose DB		Placebo, Then RO7239361 Low Dose OL		Placebo, Then RO7239361 High Dose OL		RO7239361 Low Dose, Then RO7239361 Low Dose OL		RO7239361 High Dose, Then RO7239361 High Dose OL
Arm/Group Description	Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period.		Participants received low dose RO7239361 SC on specified days of the 48-week DB period.		Participants received high dose RO7239361 SC on specified days of the 48-week DB period.		Participants received matching placebo solution SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label (OL) period followed by 24 weeks of follow-up.		Participants received matching placebo solution SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.		Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.		Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up
All Cause Mortality
	Placebo DB		RO7239361 Low Dose DB		RO7239361 High Dose DB		Placebo, Then RO7239361 Low Dose OL		Placebo, Then RO7239361 High Dose OL		RO7239361 Low Dose, Then RO7239361 Low Dose OL		RO7239361 High Dose, Then RO7239361 High Dose OL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0%)		0/55 (0%)		1/55 (1.8%)		0/14 (0%)		0/13 (0%)		0/24 (0%)		0/29 (0%)
Serious Adverse Events
	Placebo DB		RO7239361 Low Dose DB		RO7239361 High Dose DB		Placebo, Then RO7239361 Low Dose OL		Placebo, Then RO7239361 High Dose OL		RO7239361 Low Dose, Then RO7239361 Low Dose OL		RO7239361 High Dose, Then RO7239361 High Dose OL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/56 (5.4%)		2/55 (3.6%)		4/55 (7.3%)		0/14 (0%)		0/13 (0%)		0/24 (0%)		0/29 (0%)
Cardiac disorders
Cardiac arrest	0/56 (0%)	0	0/55 (0%)	0	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Myocarditis	1/56 (1.8%)	1	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Supraventricular tachycardia	0/56 (0%)	0	0/55 (0%)	0	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
General disorders
Influenza like illness	1/56 (1.8%)	1	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	0/56 (0%)	0	0/55 (0%)	0	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Infections and infestations
Gastrointestinal viral infection	1/56 (1.8%)	1	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Viral infection	0/56 (0%)	0	1/55 (1.8%)	1	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Injury, poisoning and procedural complications
Humerus fracture	0/56 (0%)	0	1/55 (1.8%)	1	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Overdose	0/56 (0%)	0	0/55 (0%)	0	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Metabolism and nutrition disorders
Hypocalcaemia	1/56 (1.8%)	1	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo DB		RO7239361 Low Dose DB		RO7239361 High Dose DB		Placebo, Then RO7239361 Low Dose OL		Placebo, Then RO7239361 High Dose OL		RO7239361 Low Dose, Then RO7239361 Low Dose OL		RO7239361 High Dose, Then RO7239361 High Dose OL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/56 (76.8%)		43/55 (78.2%)		47/55 (85.5%)		8/14 (57.1%)		7/13 (53.8%)		13/24 (54.2%)		12/29 (41.4%)
Ear and labyrinth disorders
Ear pain	1/56 (1.8%)	1	1/55 (1.8%)	1	4/55 (7.3%)	7	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/56 (1.8%)	2	1/55 (1.8%)	1	1/55 (1.8%)	1	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	0/29 (0%)	0
Abdominal pain	1/56 (1.8%)	1	2/55 (3.6%)	2	3/55 (5.5%)	5	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Abdominal pain upper	3/56 (5.4%)	4	4/55 (7.3%)	5	7/55 (12.7%)	12	0/14 (0%)	0	0/13 (0%)	0	1/24 (4.2%)	1	1/29 (3.4%)	2
Constipation	4/56 (7.1%)	5	4/55 (7.3%)	4	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	1/24 (4.2%)	1	0/29 (0%)	0
Diarrhoea	3/56 (5.4%)	3	10/55 (18.2%)	13	4/55 (7.3%)	8	0/14 (0%)	0	0/13 (0%)	0	1/24 (4.2%)	1	2/29 (6.9%)	2
Dyspepsia	0/56 (0%)	0	1/55 (1.8%)	1	3/55 (5.5%)	4	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Nausea	1/56 (1.8%)	1	2/55 (3.6%)	2	5/55 (9.1%)	9	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	4/29 (13.8%)	4
Vomiting	6/56 (10.7%)	6	8/55 (14.5%)	14	6/55 (10.9%)	11	0/14 (0%)	0	0/13 (0%)	0	3/24 (12.5%)	4	2/29 (6.9%)	2
General disorders
Fatigue	0/56 (0%)	0	4/55 (7.3%)	4	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/24 (4.2%)	1	1/29 (3.4%)	1
Gait inability	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	0/29 (0%)	0
Injection site bruising	2/56 (3.6%)	3	4/55 (7.3%)	4	4/55 (7.3%)	4	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Injection site erythema	8/56 (14.3%)	25	11/55 (20%)	43	12/55 (21.8%)	38	0/14 (0%)	0	3/13 (23.1%)	17	2/24 (8.3%)	6	1/29 (3.4%)	1
Injection site induration	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Injection site oedema	3/56 (5.4%)	7	2/55 (3.6%)	9	1/55 (1.8%)	9	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Injection site pruritus	0/56 (0%)	0	2/55 (3.6%)	2	2/55 (3.6%)	6	0/14 (0%)	0	1/13 (7.7%)	12	0/24 (0%)	0	0/29 (0%)	0
Injection site reaction	2/56 (3.6%)	3	4/55 (7.3%)	29	2/55 (3.6%)	33	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Injection site swelling	0/56 (0%)	0	4/55 (7.3%)	31	3/55 (5.5%)	5	0/14 (0%)	0	0/13 (0%)	0	1/24 (4.2%)	1	1/29 (3.4%)	1
Localised oedema	3/56 (5.4%)	5	0/55 (0%)	0	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Pyrexia	8/56 (14.3%)	8	9/55 (16.4%)	13	8/55 (14.5%)	9	2/14 (14.3%)	2	1/13 (7.7%)	1	3/24 (12.5%)	3	1/29 (3.4%)	1
Infections and infestations
Ear infection	0/56 (0%)	0	4/55 (7.3%)	4	1/55 (1.8%)	2	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Gastroenteritis	1/56 (1.8%)	2	1/55 (1.8%)	1	3/55 (5.5%)	5	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Gastroenteritis viral	1/56 (1.8%)	1	1/55 (1.8%)	1	1/55 (1.8%)	1	1/14 (7.1%)	1	0/13 (0%)	0	1/24 (4.2%)	1	0/29 (0%)	0
Hordeolum	0/56 (0%)	0	2/55 (3.6%)	2	0/55 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	1/29 (3.4%)	1
Influenza	3/56 (5.4%)	3	6/55 (10.9%)	6	1/55 (1.8%)	1	0/14 (0%)	0	0/13 (0%)	0	2/24 (8.3%)	2	0/29 (0%)	0
Nasopharyngitis	13/56 (23.2%)	17	13/55 (23.6%)	17	13/55 (23.6%)	16	2/14 (14.3%)	2	0/13 (0%)	0	0/24 (0%)	0	2/29 (6.9%)	2
Pharyngitis	2/56 (3.6%)	2	2/55 (3.6%)	2	3/55 (5.5%)	3	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	0/29 (0%)	0
Rhinitis	1/56 (1.8%)	1	3/55 (5.5%)	5	4/55 (7.3%)	7	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Sinusitis	1/56 (1.8%)	1	0/55 (0%)	0	3/55 (5.5%)	4	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Upper respiratory tract infection	6/56 (10.7%)	8	4/55 (7.3%)	5	7/55 (12.7%)	16	1/14 (7.1%)	1	1/13 (7.7%)	1	0/24 (0%)	0	2/29 (6.9%)	2
Injury, poisoning and procedural complications
Contusion	2/56 (3.6%)	2	5/55 (9.1%)	7	4/55 (7.3%)	5	0/14 (0%)	0	1/13 (7.7%)	2	0/24 (0%)	0	2/29 (6.9%)	2
Fall	5/56 (8.9%)	11	1/55 (1.8%)	1	5/55 (9.1%)	6	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	1/29 (3.4%)	1
Gadolinium deposition disease	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Ligament sprain	4/56 (7.1%)	4	1/55 (1.8%)	2	1/55 (1.8%)	1	2/14 (14.3%)	2	0/13 (0%)	0	3/24 (12.5%)	3	1/29 (3.4%)	1
Skin abrasion	2/56 (3.6%)	3	3/55 (5.5%)	12	0/55 (0%)	0	1/14 (7.1%)	3	0/13 (0%)	0	1/24 (4.2%)	4	1/29 (3.4%)	1
Thermal burn	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Investigations
Bone density decreased	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	0/29 (0%)	0
Glutamate dehydrogenase increased	2/56 (3.6%)	2	1/55 (1.8%)	1	3/55 (5.5%)	3	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	6/56 (10.7%)	6	7/55 (12.7%)	8	5/55 (9.1%)	6	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	1/29 (3.4%)	1
Back pain	4/56 (7.1%)	4	7/55 (12.7%)	9	2/55 (3.6%)	2	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	1/29 (3.4%)	1
Mobility decreased	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	0/29 (0%)	0
Muscle spasms	1/56 (1.8%)	1	2/55 (3.6%)	7	2/55 (3.6%)	6	1/14 (7.1%)	1	2/13 (15.4%)	2	0/24 (0%)	0	1/29 (3.4%)	1
Pain in extremity	2/56 (3.6%)	3	4/55 (7.3%)	6	8/55 (14.5%)	11	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Nervous system disorders
Headache	9/56 (16.1%)	28	14/55 (25.5%)	60	10/55 (18.2%)	42	1/14 (7.1%)	3	0/13 (0%)	0	2/24 (8.3%)	9	2/29 (6.9%)	4
Migraine	0/56 (0%)	0	1/55 (1.8%)	10	0/55 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	1/24 (4.2%)	3	0/29 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	10/56 (17.9%)	10	8/55 (14.5%)	11	7/55 (12.7%)	13	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	1/29 (3.4%)	2
Epistaxis	3/56 (5.4%)	9	3/55 (5.5%)	15	6/55 (10.9%)	17	0/14 (0%)	0	1/13 (7.7%)	1	0/24 (0%)	0	0/29 (0%)	0
Nasal congestion	1/56 (1.8%)	1	3/55 (5.5%)	3	3/55 (5.5%)	3	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	2/29 (6.9%)	2
Productive cough	0/56 (0%)	0	3/55 (5.5%)	3	0/55 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Rhinorrhoea	1/56 (1.8%)	1	4/55 (7.3%)	7	3/55 (5.5%)	3	1/14 (7.1%)	2	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Skin and subcutaneous tissue disorders
Erythema	3/56 (5.4%)	4	2/55 (3.6%)	2	1/55 (1.8%)	1	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Rash	4/56 (7.1%)	9	4/55 (7.3%)	5	7/55 (12.7%)	9	0/14 (0%)	0	0/13 (0%)	0	1/24 (4.2%)	1	1/29 (3.4%)	1
Rash macular	0/56 (0%)	0	0/55 (0%)	0	0/55 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0
Urticaria	3/56 (5.4%)	4	2/55 (3.6%)	2	3/55 (5.5%)	4	0/14 (0%)	0	0/13 (0%)	0	0/24 (0%)	0	0/29 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.