Muscular Dystrophy (DMD)
Conditions
Brief summary
The purpose of this study is to determine the safety and tolerability of RO7239361 in boys with Duchenne Muscular Dystrophy with any genetic mutation.
Interventions
DRUGRO7239361
Colorless to slightly yellow, clear to opalescent solution, essentially free of particulate matter packaged in a 1 cc glass syringe equipped with a safety syringe device.
DRUGPlacebo
Colorless to slightly yellow, clear to opalescent solution, essentially free of particulate matter packaged in a 1 cc glass syringe equipped with a safety syringe device.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
5 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with DMD * Able to walk without assistance * Able to walk up 4 stairs in 8 seconds or less * Weigh at least 15 kg * Taking corticosteroids for DMD
Exclusion criteria
* Ejection fraction \< 55% on echocardiogram, based on central read * 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 * Treatment with exon skipping therapies 6 months prior to study start * Treatment with ataluren or any investigational drug currently or within 5 half-lives prior to study start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Summary for the 24 Week Double-Blind Phase | Baseline to Week 24 | Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 24. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Safety Summary up to Week 72 | Baseline to Week 72 | Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 72. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration. Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW. Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 6. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose. | Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | PK parameter estimates at steady state following approximately 12 weeks QW administration. Panel 3 = 50 mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration. Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 8. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 50 mg QW Dose. | Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | PK parameter estimates at steady state following approximately 12 weeks QW administration. Panel 3 = 50 mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| RO7239361 Trough Concentrations | Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | Trough concentrations of RO7239361 at different dose levels. Panel 1 = 4mg, Panel 2 = 12.5mg and 20mg, Panel 3 = 35mg, Expansion Panels = 35mg and 50mg. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | Day 8 through Week 24, baseline and on-study information represented in table. | A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | Day 8 through Week 72, baseline and on-study information represented in table. | A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample. Double-blind phase data for placebo participants is not included. Placebo participants in each arm moved on to RO7239361 upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Serum Concentration of Free Myostatin in the Double-Blind Phase | Baseline through Week 24 | Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | Day 1: predose, 3, 6, 72 and 96 hours (h) postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration. Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. No participants received the Panel 2 20mg dose. |
| Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Baseline through Week 24 | Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | Baseline through Week 24 | Ratio of contractile vs non-contractile content is contractile content / non-contractile content. Fold change from baseline of the ratio is defined as the ratio of fold change from baseline of contractile content vs fold change from baseline of non-contractile content. Right thigh measurements. W12 = Week 12, W24 = Week 24. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | Baseline through Week 24 | Right thigh measurements. W12 = Week 12, W24 = Week 24. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | Day 8 through Week 228, baseline and on-study information represented in table. | A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample. Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Serum Concentration of Free Myostatin, Whole Study | Baseline through Week 252 | Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Percent Inhibition of Free Myostatin, Whole Study | Baseline through Week 252 | Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Serum Concentration of Drug-Myostatin Complex, Whole Study | Baseline through Week 252 | Participants in the Placebo arm received placebo during the double-blind (DB) period (up to Week 24) and received RO7239361 during the open label (OL) phase. PFS in table row title indicates when study drug was changed from vial to prefilled syringe (PFS). Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Percent Inhibition of Free Myostatin in the Double-Blind Phase | Baseline through Week 24 | Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
| Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose. | Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose | PK parameter estimates at steady state following approximately 12 weeks QW administration. Panel 3 = 50 mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. |
Countries
Canada, United States
Participant flow
Recruitment details
Doses for this study are based upon achieving a moderate to high degree of suppression in serum free myostatin at steady-state trough across 3 dose levels. A body weight-tiered, fixed-dose strategy targeting moderate (\>50%), high (\>85%) and near complete (\>95%) suppression of serum free myostatin was used to select the three doses for the study.
Pre-assignment details
Starting at Week 5, participants whose weight exceeded or dropped below the dosing weight tier to which they were assigned (by \>1kg) were assigned to the new corresponding body weight-based dose within the participants assigned panel.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo subcutaneous injections on specified days | 11 |
| Panel 1 RO7239361 RO7239361 subcutaneous injections on specified days. The Panel 1 dose targets achievement of \> 50% suppression in levels of free myostatin at trough after 5 weeks of weekly dosing. The Panel 1 body weight tier dose is \>15kg at a dose of 4 mg (milligram) /0.8 mL (millilitre). | 7 |
| Panel 2 RO7239361 RO7239361 subcutaneous injections on specified days. The Panel 2 dose targets achievement of \> 85% suppression in levels of free myostatin at trough after 5 weeks of weekly dosing. Panel 2 body weight tier doses are =\>15kg to =\< 45kg at a dose of 12.5 mg /0.25 mL and =\>45kg at a dose of 20 mg /0.4 mL | 6 |
| Panel 3 and Expansion Panel RO7239361 RO7239361 subcutaneous injections on specified days. The Panel 3 and Expansion Panel dose targets achievement of \> 95% suppression in levels of free myostatin at trough after 5 weeks of weekly dosing. Panel 3 and Expansion body weight tier doses are =\>15kg to =\< 45kg at a dose of 35 mg /0.7 mL and =\>45kg at a dose of 50 mg /1.0 mL | 19 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 228 Week Open-Label Phase | Administrative Reason by Sponsor | 0 | 7 | 2 | 17 |
| 228 Week Open-Label Phase | Lack of Efficacy | 0 | 0 | 1 | 0 |
| 228 Week Open-Label Phase | Missing | 0 | 2 | 2 | 2 |
| 228 Week Open-Label Phase | Other | 0 | 0 | 1 | 4 |
| 228 Week Open-Label Phase | Subject Request to Discontinue Treatment | 0 | 0 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Panel 1 RO7239361 | Panel 2 RO7239361 | Panel 3 and Expansion Panel RO7239361 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 8.8 Years STANDARD_DEVIATION 1.33 | 8.0 Years STANDARD_DEVIATION 2.24 | 8.0 Years STANDARD_DEVIATION 1.79 | 8.1 Years STANDARD_DEVIATION 1.81 | 8.2 Years STANDARD_DEVIATION 1.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 7 Participants | 5 Participants | 13 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 6 Participants | 3 Participants | 13 Participants | 31 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 6 Participants | 19 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 7 | 0 / 6 | 0 / 19 | 0 / 9 | 0 / 8 | 0 / 26 |
| other Total, other adverse events | 9 / 11 | 5 / 7 | 6 / 6 | 17 / 19 | 9 / 9 | 6 / 8 | 24 / 26 |
| serious Total, serious adverse events | 1 / 11 | 0 / 7 | 0 / 6 | 1 / 19 | 1 / 9 | 2 / 8 | 1 / 26 |
Outcome results
Primary
Safety Summary for the 24 Week Double-Blind Phase
Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 24. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline to Week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | Related AEs | 27.3 percentage of participants |
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | Very Severe AEs | 0 percentage of participants |
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | Serious Adverse Events (SAE) | 9.1 percentage of participants |
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | Death | 0 percentage of participants |
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | Severe AEs | 0 percentage of participants |
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | Adverse Events (AEs) | 81.8 percentage of participants |
| Placebo | Safety Summary for the 24 Week Double-Blind Phase | AEs leading to study withdrawal | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Very Severe AEs | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | AEs leading to study withdrawal | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Adverse Events (AEs) | 71.4 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Serious Adverse Events (SAE) | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Severe AEs | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Death | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Related AEs | 14.3 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | AEs leading to study withdrawal | 0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Related AEs | 50.0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Death | 0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Adverse Events (AEs) | 100.0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Serious Adverse Events (SAE) | 0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Very Severe AEs | 0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Severe AEs | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Adverse Events (AEs) | 94.7 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Severe AEs | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Very Severe AEs | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Death | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Related AEs | 36.8 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | Serious Adverse Events (SAE) | 5.3 percentage of participants |
| Panel 3 and Expansion RO7239361 | Safety Summary for the 24 Week Double-Blind Phase | AEs leading to study withdrawal | 0 percentage of participants |
Primary
Safety Summary up to Week 72
Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 72. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline to Week 72
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety Summary up to Week 72 | Adverse Events (AEs) | 100.0 percentage of participants |
| Placebo | Safety Summary up to Week 72 | Very Severe AEs | 0 percentage of participants |
| Placebo | Safety Summary up to Week 72 | Serious Adverse Events (SAE) | 0 percentage of participants |
| Placebo | Safety Summary up to Week 72 | Death | 0 percentage of participants |
| Placebo | Safety Summary up to Week 72 | Related AEs | 77.8 percentage of participants |
| Placebo | Safety Summary up to Week 72 | Severe AEs | 0 percentage of participants |
| Placebo | Safety Summary up to Week 72 | AEs leading to study withdrawal | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | Serious Adverse Events (SAE) | 25.0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | Death | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | Adverse Events (AEs) | 100.0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | AEs leading to study withdrawal | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | Very Severe AEs | 0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | Severe AEs | 25.0 percentage of participants |
| Panel 1 RO7239361 | Safety Summary up to Week 72 | Related AEs | 62.5 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | Very Severe AEs | 0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | Adverse Events (AEs) | 96.2 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | Related AEs | 50.0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | Severe AEs | 3.8 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | Serious Adverse Events (SAE) | 7.7 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | AEs leading to study withdrawal | 0 percentage of participants |
| Panel 2 RO7239361 | Safety Summary up to Week 72 | Death | 0 percentage of participants |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses.
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration. Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 8. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 18676 ng•day/mL | Geometric Coefficient of Variation 23 |
| Panel 1 RO7239361 | Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 51461 ng•day/mL | Geometric Coefficient of Variation 18 |
| Panel 2 RO7239361 | Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 150609 ng•day/mL | Geometric Coefficient of Variation 24 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 50 mg QW Dose.
PK parameter estimates at steady state following approximately 12 weeks QW administration. Panel 3 = 50 mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 50 mg QW Dose. | 151000 ng•day/mL |
Secondary
Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase
Right thigh measurements. W12 = Week 12, W24 = Week 24. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 24
Population: The pharmacodynamics (PD) data set includes all available data from subjects for whom PD measurements are available at baseline and at least one other timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24:RECTUS FEMORIS | 8.97 Percentage Change | Standard Error 10.214 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 39.21 Percentage Change | Standard Error 19.76 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS LATERALIS | 31.47 Percentage Change | Standard Error 39.343 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 34.17 Percentage Change | Standard Error 24.918 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS MEDIALIS | -17.89 Percentage Change | Standard Error 19.358 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS LATERALIS | 12.95 Percentage Change | Standard Error 35.465 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 11.69 Percentage Change | Standard Error 15.626 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 31.01 Percentage Change | Standard Error 24.708 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: GRACILIS | 20.14 Percentage Change | Standard Error 15.489 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 14.86 Percentage Change | Standard Error 15.072 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 34.24 Percentage Change | Standard Error 18.328 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS MEDIALIS | -9.09 Percentage Change | Standard Error 11.856 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMITENDINOSUS | 32.00 Percentage Change | Standard Error 16.102 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 14.10 Percentage Change | Standard Error 7.724 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12:RECTUS FEMORIS | -7.86 Percentage Change | Standard Error 14.391 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 45.83 Percentage Change | Standard Error 14.896 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SARTORIUS | 10.75 Percentage Change | Standard Error 7.136 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SARTORIUS | 11.26 Percentage Change | Standard Error 6.584 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 39.11 Percentage Change | Standard Error 15.041 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: GRACILIS | 8.14 Percentage Change | Standard Error 7.148 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMITENDINOSUS | 25.03 Percentage Change | Standard Error 9.409 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 7.29 Percentage Change | Standard Error 16.559 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 20.09 Percentage Change | Standard Error 9.818 |
| Placebo | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 10.47 Percentage Change | Standard Error 12.16 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 7.45 Percentage Change | Standard Error 11.592 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 32.57 Percentage Change | Standard Error 19.133 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 42.84 Percentage Change | Standard Error 22.086 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS LATERALIS | 38.32 Percentage Change | Standard Error 19.57 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS MEDIALIS | 9.82 Percentage Change | Standard Error 6.965 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 21.90 Percentage Change | Standard Error 12.345 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SARTORIUS | 0.81 Percentage Change | Standard Error 8.143 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12:RECTUS FEMORIS | 10.33 Percentage Change | Standard Error 11.927 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS MEDIALIS | 15.65 Percentage Change | Standard Error 8.463 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: GRACILIS | 43.00 Percentage Change | Standard Error 28.539 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 23.41 Percentage Change | Standard Error 13.199 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 11.83 Percentage Change | Standard Error 13.013 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 43.01 Percentage Change | Standard Error 11.506 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24:RECTUS FEMORIS | 7.68 Percentage Change | Standard Error 13.082 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 24.12 Percentage Change | Standard Error 11.804 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 23.35 Percentage Change | Standard Error 12.704 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SARTORIUS | 6.59 Percentage Change | Standard Error 11.952 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMITENDINOSUS | 36.17 Percentage Change | Standard Error 23.285 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS LATERALIS | 47.79 Percentage Change | Standard Error 26.178 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 33.43 Percentage Change | Standard Error 35.009 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 8.31 Percentage Change | Standard Error 11.767 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: GRACILIS | 18.72 Percentage Change | Standard Error 16.757 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 30.01 Percentage Change | Standard Error 18.631 |
| Panel 1 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMITENDINOSUS | -1.24 Percentage Change | Standard Error 10.973 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | -3.73 Percentage Change | Standard Error 29.037 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: GRACILIS | 15.28 Percentage Change | Standard Error 8.693 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 16.56 Percentage Change | Standard Error 19.998 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 5.85 Percentage Change | Standard Error 11.074 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 16.72 Percentage Change | Standard Error 17.806 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 2.69 Percentage Change | Standard Error 13.733 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12:RECTUS FEMORIS | -3.56 Percentage Change | Standard Error 14.175 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SARTORIUS | -0.85 Percentage Change | Standard Error 6.383 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMITENDINOSUS | 33.00 Percentage Change | Standard Error 26.73 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | -52.03 Percentage Change | Standard Error 71.421 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS LATERALIS | 14.08 Percentage Change | Standard Error 27.902 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS MEDIALIS | -11.60 Percentage Change | Standard Error 15.849 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 12.81 Percentage Change | Standard Error 16.393 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | -6.71 Percentage Change | Standard Error 37.311 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | -5.32 Percentage Change | Standard Error 29.14 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | -0.44 Percentage Change | Standard Error 16.183 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: GRACILIS | 11.21 Percentage Change | Standard Error 5.461 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24:RECTUS FEMORIS | -10.01 Percentage Change | Standard Error 16.121 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SARTORIUS | -14.18 Percentage Change | Standard Error 9.481 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | -11.48 Percentage Change | Standard Error 24.468 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMITENDINOSUS | 24.16 Percentage Change | Standard Error 23.403 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | -68.05 Percentage Change | Standard Error 86.362 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS LATERALIS | 32.64 Percentage Change | Standard Error 30.136 |
| Panel 2 RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS MEDIALIS | -13.74 Percentage Change | Standard Error 29.664 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 14.61 Percentage Change | Standard Error 9.755 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 33.70 Percentage Change | Standard Error 12.073 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMITENDINOSUS | 36.69 Percentage Change | Standard Error 14.802 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 30.01 Percentage Change | Standard Error 13.494 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 46.70 Percentage Change | Standard Error 16.48 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS MEDIALIS | 10.46 Percentage Change | Standard Error 12.093 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: GRACILIS | 48.95 Percentage Change | Standard Error 17.064 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SARTORIUS | 10.81 Percentage Change | Standard Error 11.017 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS LATERALIS | 45.41 Percentage Change | Standard Error 43.774 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24:RECTUS FEMORIS | 55.65 Percentage Change | Standard Error 27.535 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12:RECTUS FEMORIS | 34.91 Percentage Change | Standard Error 6.037 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SARTORIUS | 16.63 Percentage Change | Standard Error 4.476 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 18.68 Percentage Change | Standard Error 7.479 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 61.03 Percentage Change | Standard Error 25.524 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 19.22 Percentage Change | Standard Error 9.802 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: GRACILIS | 27.02 Percentage Change | Standard Error 5.686 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMITENDINOSUS | 73.68 Percentage Change | Standard Error 17.594 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 53.20 Percentage Change | Standard Error 25.328 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS MEDIALIS | 21.14 Percentage Change | Standard Error 9.746 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 41.63 Percentage Change | Standard Error 34.926 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 17.15 Percentage Change | Standard Error 15.484 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS LATERALIS | 57.86 Percentage Change | Standard Error 34.026 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 45.05 Percentage Change | Standard Error 27.52 |
| Panel 3 and Expansion RO7239361 | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | -0.81 Percentage Change | Standard Error 19.353 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 23.93 Percentage Change | Standard Error 11.289 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: GRACILIS | 23.22 Percentage Change | Standard Error 5.44 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 31.33 Percentage Change | Standard Error 13.37 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 4.41 Percentage Change | Standard Error 52.393 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 31.01 Percentage Change | Standard Error 10.564 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 10.44 Percentage Change | Standard Error 7.344 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 49.49 Percentage Change | Standard Error 12.011 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 18.60 Percentage Change | Standard Error 5.394 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 22.55 Percentage Change | Standard Error 8.284 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SARTORIUS | 18.20 Percentage Change | Standard Error 5.519 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 4.01 Percentage Change | Standard Error 54.787 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: SEMITENDINOSUS | 40.10 Percentage Change | Standard Error 10.18 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: GRACILIS | 40.15 Percentage Change | Standard Error 8.382 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 44.12 Percentage Change | Standard Error 13.323 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12:RECTUS FEMORIS | 16.01 Percentage Change | Standard Error 9.888 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SEMITENDINOSUS | 62.55 Percentage Change | Standard Error 11.073 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS LATERALIS | 22.73 Percentage Change | Standard Error 15.138 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24:RECTUS FEMORIS | 38.40 Percentage Change | Standard Error 14.293 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 29.98 Percentage Change | Standard Error 8.53 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 9.84 Percentage Change | Standard Error 3.882 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS LATERALIS | 46.87 Percentage Change | Standard Error 20.919 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: VASTUS MEDIALIS | 23.94 Percentage Change | Standard Error 11.321 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W24: SARTORIUS | 25.51 Percentage Change | Standard Error 6.404 |
| Expansion Panel RO7239361 35mg | Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase | W12: VASTUS MEDIALIS | 17.89 Percentage Change | Standard Error 6.788 |
Secondary
Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase
Ratio of contractile vs non-contractile content is contractile content / non-contractile content. Fold change from baseline of the ratio is defined as the ratio of fold change from baseline of contractile content vs fold change from baseline of non-contractile content. Right thigh measurements. W12 = Week 12, W24 = Week 24. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 24
Population: The pharmacodynamics (PD) data set includes all available data from subjects for whom PD measurements are available at baseline and at least one other timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS LATERALIS | 0.66 Fold Change | Standard Error 0.16 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 2.59 Fold Change | Standard Error 1.749 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12:RECTUS FEMORIS | 0.74 Fold Change | Standard Error 0.185 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: GRACILIS | 1.43 Fold Change | Standard Error 0.686 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMITENDINOSUS | 0.78 Fold Change | Standard Error 0.262 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 0.82 Fold Change | Standard Error 0.23 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 0.69 Fold Change | Standard Error 0.104 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SARTORIUS | 1.78 Fold Change | Standard Error 0.771 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: GRACILIS | 1.13 Fold Change | Standard Error 0.318 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 0.95 Fold Change | Standard Error 0.412 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 0.66 Fold Change | Standard Error 0.126 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 0.92 Fold Change | Standard Error 0.269 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 0.91 Fold Change | Standard Error 0.195 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMITENDINOSUS | 0.56 Fold Change | Standard Error 0.119 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS LATERALIS | 0.78 Fold Change | Standard Error 0.159 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SARTORIUS | 1.90 Fold Change | Standard Error 0.872 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 1.04 Fold Change | Standard Error 0.291 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 1.07 Fold Change | Standard Error 0.511 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 0.66 Fold Change | Standard Error 0.112 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS MEDIALIS | 2.14 Fold Change | Standard Error 0.889 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24:RECTUS FEMORIS | 0.94 Fold Change | Standard Error 0.256 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 0.81 Fold Change | Standard Error 0.29 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS MEDIALIS | 1.08 Fold Change | Standard Error 0.269 |
| Placebo | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 0.78 Fold Change | Standard Error 0.221 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 0.94 Fold Change | Standard Error 0.304 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 0.95 Fold Change | Standard Error 0.088 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMITENDINOSUS | 1.59 Fold Change | Standard Error 0.52 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 1.47 Fold Change | Standard Error 0.446 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: GRACILIS | 7.57 Fold Change | Standard Error 5.372 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS LATERALIS | 1.88 Fold Change | Standard Error 0.905 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS MEDIALIS | 5.16 Fold Change | Standard Error 3.58 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12:RECTUS FEMORIS | 0.55 Fold Change | Standard Error 0.134 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SARTORIUS | 0.69 Fold Change | Standard Error 0.307 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 0.88 Fold Change | Standard Error 0.283 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 0.82 Fold Change | Standard Error 0.284 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMITENDINOSUS | 2.95 Fold Change | Standard Error 1.016 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 1.11 Fold Change | Standard Error 0.292 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS LATERALIS | 0.89 Fold Change | Standard Error 0.272 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS MEDIALIS | 1.26 Fold Change | Standard Error 0.112 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 0.90 Fold Change | Standard Error 0.361 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 1.14 Fold Change | Standard Error 0.269 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 0.94 Fold Change | Standard Error 0.296 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 1.13 Fold Change | Standard Error 0.315 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 2.24 Fold Change | Standard Error 1.027 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: GRACILIS | 3.03 Fold Change | Standard Error 2.564 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 2.77 Fold Change | Standard Error 1.144 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24:RECTUS FEMORIS | 0.84 Fold Change | Standard Error 0.22 |
| Panel 1 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SARTORIUS | 0.73 Fold Change | Standard Error 0.207 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 0.62 Fold Change | Standard Error 0.258 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMITENDINOSUS | 1.43 Fold Change | Standard Error 0.524 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS LATERALIS | 1.10 Fold Change | Standard Error 0.333 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 1.16 Fold Change | Standard Error 0.33 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS MEDIALIS | 2.97 Fold Change | Standard Error 1.981 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24:RECTUS FEMORIS | 7.43 Fold Change | Standard Error 6.216 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS MEDIALIS | 6.01 Fold Change | Standard Error 5.478 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 1.11 Fold Change | Standard Error 0.471 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 1.57 Fold Change | Standard Error 0.556 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: GRACILIS | 0.98 Fold Change | Standard Error 0.176 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 2.03 Fold Change | Standard Error 1.564 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 0.59 Fold Change | Standard Error 0.144 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 1.00 Fold Change | Standard Error 0.349 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS LATERALIS | 1.45 Fold Change | Standard Error 0.596 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 0.72 Fold Change | Standard Error 0.157 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 2.15 Fold Change | Standard Error 1.003 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 0.63 Fold Change | Standard Error 0.355 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SARTORIUS | 1.04 Fold Change | Standard Error 0.443 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SARTORIUS | 0.78 Fold Change | Standard Error 0.375 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 1.47 Fold Change | Standard Error 0.777 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 1.12 Fold Change | Standard Error 0.281 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12:RECTUS FEMORIS | 4.49 Fold Change | Standard Error 2.729 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: GRACILIS | 1.37 Fold Change | Standard Error 0.465 |
| Panel 2 RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMITENDINOSUS | 1.31 Fold Change | Standard Error 0.26 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 0.94 Fold Change | Standard Error 0.25 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 0.86 Fold Change | Standard Error 0.157 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: GRACILIS | 1.45 Fold Change | Standard Error 0.748 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: GRACILIS | 3.41 Fold Change | Standard Error 2.474 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12:RECTUS FEMORIS | 0.99 Fold Change | Standard Error 0.345 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 1.29 Fold Change | Standard Error 0.238 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS LATERALIS | 1.78 Fold Change | Standard Error 0.455 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 2.27 Fold Change | Standard Error 1.122 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS MEDIALIS | 1.29 Fold Change | Standard Error 0.474 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 0.79 Fold Change | Standard Error 0.162 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 0.96 Fold Change | Standard Error 0.095 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS MEDIALIS | 0.85 Fold Change | Standard Error 0.28 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SARTORIUS | 3.24 Fold Change | Standard Error 1.85 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 0.86 Fold Change | Standard Error 0.276 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24:RECTUS FEMORIS | 0.80 Fold Change | Standard Error 0.262 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 1.24 Fold Change | Standard Error 0.411 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 1.36 Fold Change | Standard Error 0.718 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMITENDINOSUS | 1.42 Fold Change | Standard Error 0.317 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 0.93 Fold Change | Standard Error 0.255 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SARTORIUS | 0.90 Fold Change | Standard Error 0.396 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMITENDINOSUS | 1.04 Fold Change | Standard Error 0.254 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 1.61 Fold Change | Standard Error 0.697 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 1.10 Fold Change | Standard Error 0.28 |
| Panel 3 and Expansion RO7239361 | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS LATERALIS | 1.43 Fold Change | Standard Error 0.256 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS MEDIALIS | 3.50 Fold Change | Standard Error 1.39 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR LONGUS | 2.36 Fold Change | Standard Error 0.875 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: ADDUCTOR MAGNUS | 1.04 Fold Change | Standard Error 0.101 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS LONG | 1.26 Fold Change | Standard Error 0.237 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: BICEPS FEMORIS SHORT | 1.31 Fold Change | Standard Error 0.301 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: GRACILIS | 5.42 Fold Change | Standard Error 3.871 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12:RECTUS FEMORIS | 2.02 Fold Change | Standard Error 0.764 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SARTORIUS | 2.00 Fold Change | Standard Error 0.683 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMIMEMBRANOSUS | 1.31 Fold Change | Standard Error 0.194 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: SEMITENDINOSUS | 1.17 Fold Change | Standard Error 0.16 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS INTERMEDIUS | 1.64 Fold Change | Standard Error 0.377 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS LATERALIS | 1.70 Fold Change | Standard Error 0.334 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W12: VASTUS MEDIALIS | 5.96 Fold Change | Standard Error 3.376 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR LONGUS | 2.41 Fold Change | Standard Error 0.813 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: ADDUCTOR MAGNUS | 1.14 Fold Change | Standard Error 0.146 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS LONG | 2.10 Fold Change | Standard Error 1.044 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: BICEPS FEMORIS SHORT | 2.02 Fold Change | Standard Error 0.416 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: GRACILIS | 5.17 Fold Change | Standard Error 3.54 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24:RECTUS FEMORIS | 3.01 Fold Change | Standard Error 1.612 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SARTORIUS | 2.45 Fold Change | Standard Error 0.842 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMIMEMBRANOSUS | 1.39 Fold Change | Standard Error 0.256 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: SEMITENDINOSUS | 1.22 Fold Change | Standard Error 0.221 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS INTERMEDIUS | 1.47 Fold Change | Standard Error 0.318 |
| Expansion Panel RO7239361 35mg | Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase | W24: VASTUS LATERALIS | 2.03 Fold Change | Standard Error 0.484 |
Secondary
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses.
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration. Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361. No participants received the Panel 2 20mg dose.
Time frame: Day 1: predose, 3, 6, 72 and 96 hours (h) postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 3217 ng/ml | Geometric Coefficient of Variation 15.8 |
| Panel 1 RO7239361 | Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 8490 ng/ml | Geometric Coefficient of Variation 21.5 |
| Panel 2 RO7239361 | Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 24242 ng/ml | Geometric Coefficient of Variation 26.3 |
Secondary
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose.
PK parameter estimates at steady state following approximately 12 weeks QW administration. Panel 3 = 50 mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose. | 23297 ng/mL |
Secondary
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 8 through Week 24, baseline and on-study information represented in table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | Baseline (BL): ADA Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: ADA Negative | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: Missing | 100.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Persistent Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Only last sample Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Other Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Missing | 100.0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: Missing | 28.6 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Only last sample Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Other Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Missing | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative | 100.0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: ADA Negative | 71.4 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative | 100.0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Other Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Missing | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Only last sample Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: ADA Negative | 100.0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: Missing | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative | 100.0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Only last sample Positive | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Missing | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: Other Positive | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: ADA Negative | 89.5 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | BL: Missing | 10.5 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Positive | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 3 and Expansion RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
Secondary
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample. Double-blind phase data for placebo participants is not included. Placebo participants in each arm moved on to RO7239361 upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 8 through Week 72, baseline and on-study information represented in table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | Baseline (BL): ADA Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | BL: ADA Negative | 77.8 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | BL: Missing | 22.2 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Persistent Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Only last sample Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Other Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Negative | 100.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Missing | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Only last sample Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | BL: ADA Negative | 87.5 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Missing | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Negative | 100.0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | BL: Missing | 12.5 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Other Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Negative | 96.2 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Positive | 3.8 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Only last sample Positive | 3.8 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Other Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | On-treatment: Missing | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | BL: ADA Negative | 88.5 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72 | BL: Missing | 11.5 percentage of participants |
Secondary
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample. Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 8 through Week 228, baseline and on-study information represented in table.
Population: The safety population included all participants who received at least one dose of study drug. The Whole Study set reported here includes data from RO7239361-treated participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Other Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | BL: Missing | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Negative | 100.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | BL: ADA Negative | 100.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Missing | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Persistent Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Only last sample Positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | BL: ADA Negative | 87.5 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Other Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Negative | 100.0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | BL: Missing | 12.5 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Only last sample Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Missing | 0 percentage of participants |
| Panel 1 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Missing | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | Baseline (BL): ADA Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | BL: ADA Negative | 92.3 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | BL: Missing | 7.7 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Positive | 3.8 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Persistent Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Only last sample Positive | 0 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: Other Positive | 3.8 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Negative | 96.2 percentage of participants |
| Panel 2 RO7239361 | Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study | On-treatment: ADA Negative, BL Positive, No Boost | 0 percentage of participants |
Secondary
Percent Inhibition of Free Myostatin in the Double-Blind Phase
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 24
Population: The pharmacodynamics (PD) data set included all available data from subjects for whom PD measurements were available at baseline and at least one other timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 33 | 15.662 percentage inhibition | Standard Deviation 17.364 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 15 | 5.744 percentage inhibition | Standard Deviation 18.619 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 29 | 12.599 percentage inhibition | Standard Deviation 16.1591 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 8 | 23.917 percentage inhibition | Standard Deviation 31.1378 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 24 | 9.910 percentage inhibition | Standard Deviation 17.8109 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 5 | 3.114 percentage inhibition | Standard Deviation 20.3395 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 12 | 5.289 percentage inhibition | Standard Deviation 15.5082 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 22 | 5.561 percentage inhibition | Standard Deviation 11.7425 |
| Placebo | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 4 | 0.595 percentage inhibition | Standard Deviation 23.6952 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 22 | 51.836 percentage inhibition | Standard Deviation 9.3488 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 33 | 61.796 percentage inhibition | Standard Deviation 4.576 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 29 | 52.926 percentage inhibition | Standard Deviation 6.6001 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 4 | 49.689 percentage inhibition | Standard Deviation 11.7394 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 24 | 63.790 percentage inhibition | Standard Deviation 5.7031 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 5 | 46.506 percentage inhibition | Standard Deviation 9.0917 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 12 | 60.254 percentage inhibition | Standard Deviation 9.4283 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 8 | 38.411 percentage inhibition | Standard Deviation 7.032 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 15 | 40.763 percentage inhibition | Standard Deviation 10.0071 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 8 | 62.524 percentage inhibition | Standard Deviation 9.7074 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 4 | 73.533 percentage inhibition | Standard Deviation 9.8637 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 5 | 69.700 percentage inhibition | Standard Deviation 10.3411 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 15 | 77.090 percentage inhibition | Standard Deviation 6.2939 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 22 | 81.693 percentage inhibition | Standard Deviation 5.7392 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 29 | 86.894 percentage inhibition | Standard Deviation 2.959 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 33 | 91.557 percentage inhibition | Standard Deviation 2.6444 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 12 | 92.454 percentage inhibition | Standard Deviation 1.7243 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 24 | 88.392 percentage inhibition | Standard Deviation 5.1669 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 33 | 97.042 percentage inhibition | Standard Deviation 5.4443 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 15 | 96.488 percentage inhibition | Standard Deviation 1.9665 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 5 | 94.545 percentage inhibition | Standard Deviation 2.7608 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 24 | 97.921 percentage inhibition | Standard Deviation 2.2143 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Week 12 | 98.415 percentage inhibition | Standard Deviation 1.2882 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 4 | 95.334 percentage inhibition | Standard Deviation 2.4477 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 29 | 98.202 percentage inhibition | Standard Deviation 1.459 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 22 | 97.927 percentage inhibition | Standard Deviation 1.1259 |
| Panel 3 and Expansion RO7239361 | Percent Inhibition of Free Myostatin in the Double-Blind Phase | Day 8 | 84.797 percentage inhibition | Standard Deviation 22.1958 |
Secondary
Percent Inhibition of Free Myostatin, Whole Study
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 252
Population: The pharmacodynamics (PD) data set included all available data from subjects for whom PD measurements were available at baseline and at least one other timepoint. The Whole Study set reported here includes data from RO7239361-treated participants only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 5 | 46.506 percentage inhibition | Standard Deviation 9.0917 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 72 | 65.956 percentage inhibition | Standard Deviation 8.2066 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 12 | 58.934 percentage inhibition | Standard Deviation 8.7345 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 156 | 74.712 percentage inhibition | Standard Deviation 5.7764 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 60 | 66.280 percentage inhibition | Standard Deviation 8.4684 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 24 | 63.199 percentage inhibition | Standard Deviation 5.3419 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 15 | 40.763 percentage inhibition | Standard Deviation 10.0071 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 48 | 58.161 percentage inhibition | Standard Deviation 15.7101 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 25 | 62.446 percentage inhibition | Standard Deviation 7.0668 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 4 | 49.689 percentage inhibition | Standard Deviation 11.7394 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 36 | 64.103 percentage inhibition | Standard Deviation 5.3774 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 132 | 71.129 percentage inhibition | Standard Deviation 4.9576 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 22 | 51.836 percentage inhibition | Standard Deviation 9.3488 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 180 | 75.374 percentage inhibition | Standard Deviation 9.5968 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 108 | 70.498 percentage inhibition | Standard Deviation 15.2905 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 29 | 52.926 percentage inhibition | Standard Deviation 6.6001 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 8 | 38.411 percentage inhibition | Standard Deviation 7.032 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Week 84 | 54.990 percentage inhibition | Standard Deviation 11.0397 |
| Placebo | Percent Inhibition of Free Myostatin, Whole Study | Day 33 | 61.796 percentage inhibition | Standard Deviation 4.576 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 252 | 96.283 percentage inhibition | — |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 4 | 73.533 percentage inhibition | Standard Deviation 9.8637 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 5 | 69.700 percentage inhibition | Standard Deviation 10.3411 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 8 | 62.524 percentage inhibition | Standard Deviation 9.7074 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 15 | 77.090 percentage inhibition | Standard Deviation 6.2939 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 22 | 81.693 percentage inhibition | Standard Deviation 5.7392 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 29 | 86.894 percentage inhibition | Standard Deviation 2.959 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 33 | 91.557 percentage inhibition | Standard Deviation 2.6444 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 12 | 92.025 percentage inhibition | Standard Deviation 2.0548 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 24 | 89.664 percentage inhibition | Standard Deviation 5.0245 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 25 | 88.689 percentage inhibition | Standard Deviation 4.8868 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 36 | 92.057 percentage inhibition | Standard Deviation 2.63 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 48 | 92.237 percentage inhibition | Standard Deviation 3.4952 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 60 | 90.974 percentage inhibition | Standard Deviation 2.178 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 72 | 92.536 percentage inhibition | Standard Deviation 2.4445 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 84 | 92.328 percentage inhibition | Standard Deviation 5.7945 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 108 | 92.412 percentage inhibition | Standard Deviation 3.3662 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 132 | 92.935 percentage inhibition | Standard Deviation 3.8121 |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 144 | 94.732 percentage inhibition | — |
| Panel 1 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 156 | 94.881 percentage inhibition | Standard Deviation 1.3726 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 33 | 97.042 percentage inhibition | Standard Deviation 5.4443 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 5 | 94.545 percentage inhibition | Standard Deviation 2.7608 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 72 | 79.193 percentage inhibition | Standard Deviation 31.9504 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 29 | 98.202 percentage inhibition | Standard Deviation 1.459 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 8 | 84.797 percentage inhibition | Standard Deviation 22.1958 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 84 | 89.744 percentage inhibition | Standard Deviation 13.099 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 22 | 97.927 percentage inhibition | Standard Deviation 1.1259 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 4 | 95.334 percentage inhibition | Standard Deviation 2.4477 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 108 | 95.884 percentage inhibition | Standard Deviation 3.5214 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 25 | 97.974 percentage inhibition | Standard Deviation 1.8259 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Day 15 | 96.488 percentage inhibition | Standard Deviation 1.9665 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 36 | 98.470 percentage inhibition | Standard Deviation 0.841 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 24 | 98.009 percentage inhibition | Standard Deviation 1.8677 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 156 | 98.183 percentage inhibition | Standard Deviation 0.8086 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 48 | 98.036 percentage inhibition | Standard Deviation 1.4516 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 12 | 98.208 percentage inhibition | Standard Deviation 1.5605 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 132 | 96.713 percentage inhibition | Standard Deviation 2.4278 |
| Panel 2 RO7239361 | Percent Inhibition of Free Myostatin, Whole Study | Week 60 | 97.177 percentage inhibition | Standard Deviation 2.8783 |
Secondary
RO7239361 Trough Concentrations
Trough concentrations of RO7239361 at different dose levels. Panel 1 = 4mg, Panel 2 = 12.5mg and 20mg, Panel 3 = 35mg, Expansion Panels = 35mg and 50mg. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Population: Pharmacokinetic population. Panel 2, 20mg dose: the number of participants analyzed is 0 in those instances that the treatment was not administered at that visit.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | RO7239361 Trough Concentrations | Day 1 | 825.343 ng/mL | Geometric Coefficient of Variation 23 |
| Placebo | RO7239361 Trough Concentrations | Day 15 | 1258.746 ng/mL | Geometric Coefficient of Variation 35 |
| Placebo | RO7239361 Trough Concentrations | Day 84 | 2179.385 ng/mL | Geometric Coefficient of Variation 26 |
| Placebo | RO7239361 Trough Concentrations | Day 29 | 2015.695 ng/mL | Geometric Coefficient of Variation 32 |
| Placebo | RO7239361 Trough Concentrations | Day 168 | 2438.595 ng/mL | Geometric Coefficient of Variation 16 |
| Placebo | RO7239361 Trough Concentrations | Day 22 | 1640.052 ng/mL | Geometric Coefficient of Variation 15 |
| Panel 1 RO7239361 | RO7239361 Trough Concentrations | Day 22 | 4220.280 ng/mL | Geometric Coefficient of Variation 32 |
| Panel 1 RO7239361 | RO7239361 Trough Concentrations | Day 168 | 6100.315 ng/mL | Geometric Coefficient of Variation 25 |
| Panel 1 RO7239361 | RO7239361 Trough Concentrations | Day 15 | 3697.590 ng/mL | Geometric Coefficient of Variation 20 |
| Panel 1 RO7239361 | RO7239361 Trough Concentrations | Day 1 | 2115.951 ng/mL | Geometric Coefficient of Variation 20 |
| Panel 1 RO7239361 | RO7239361 Trough Concentrations | Day 29 | 5107.668 ng/mL | Geometric Coefficient of Variation 25 |
| Panel 1 RO7239361 | RO7239361 Trough Concentrations | Day 84 | 6484.502 ng/mL | Geometric Coefficient of Variation 19 |
| Panel 2 RO7239361 | RO7239361 Trough Concentrations | Day 168 | 6340.000 ng/mL | — |
| Panel 3 and Expansion RO7239361 | RO7239361 Trough Concentrations | Day 168 | 19923.182 ng/mL | Geometric Coefficient of Variation 41 |
| Panel 3 and Expansion RO7239361 | RO7239361 Trough Concentrations | Day 1 | 6559.364 ng/mL | Geometric Coefficient of Variation 26 |
| Panel 3 and Expansion RO7239361 | RO7239361 Trough Concentrations | Day 84 | 19332.421 ng/mL | Geometric Coefficient of Variation 20 |
| Panel 3 and Expansion RO7239361 | RO7239361 Trough Concentrations | Day 22 | 12383.747 ng/mL | Geometric Coefficient of Variation 30 |
| Panel 3 and Expansion RO7239361 | RO7239361 Trough Concentrations | Day 29 | 14110.005 ng/mL | Geometric Coefficient of Variation 34 |
| Panel 3 and Expansion RO7239361 | RO7239361 Trough Concentrations | Day 15 | 9957.352 ng/mL | Geometric Coefficient of Variation 34 |
| Expansion Panel RO7239361 35mg | RO7239361 Trough Concentrations | Day 15 | 9944.183 ng/mL | Geometric Coefficient of Variation 24 |
| Expansion Panel RO7239361 35mg | RO7239361 Trough Concentrations | Day 22 | 13215.188 ng/mL | Geometric Coefficient of Variation 24 |
| Expansion Panel RO7239361 35mg | RO7239361 Trough Concentrations | Day 84 | 18789.382 ng/mL | Geometric Coefficient of Variation 18 |
| Expansion Panel RO7239361 35mg | RO7239361 Trough Concentrations | Day 29 | 15094.455 ng/mL | Geometric Coefficient of Variation 19 |
| Expansion Panel RO7239361 35mg | RO7239361 Trough Concentrations | Day 1 | 6017.978 ng/mL | Geometric Coefficient of Variation 23 |
| Expansion Panel RO7239361 35mg | RO7239361 Trough Concentrations | Day 168 | 12580.299 ng/mL | Geometric Coefficient of Variation 41 |
| Expansion Panel RO7239361 50mg | RO7239361 Trough Concentrations | Day 168 | 26200.000 ng/mL | — |
| Expansion Panel RO7239361 50mg | RO7239361 Trough Concentrations | Day 29 | NA ng/mL | — |
| Expansion Panel RO7239361 50mg | RO7239361 Trough Concentrations | Day 1 | 5020.000 ng/mL | — |
| Expansion Panel RO7239361 50mg | RO7239361 Trough Concentrations | Day 15 | 9980.000 ng/mL | — |
| Expansion Panel RO7239361 50mg | RO7239361 Trough Concentrations | Day 22 | NA ng/mL | — |
| Expansion Panel RO7239361 50mg | RO7239361 Trough Concentrations | Day 84 | 27800.000 ng/mL | — |
Secondary
Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 24
Population: The pharmacodynamics (PD) data set included all available data from subjects for whom PD measurements were available at baseline and at least one other timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 8 | 4.924 ng/mL | Standard Deviation 12.9975 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 4 | 1.178 ng/mL | Standard Deviation 1.8833 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 5 | 2.119 ng/mL | Standard Deviation 2.9826 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 15 | 0.613 ng/mL | Standard Deviation 0.2102 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 22 | 1.326 ng/mL | Standard Deviation 1.341 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 29 | 1.593 ng/mL | Standard Deviation 3.1007 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 33 | 1.157 ng/mL | Standard Deviation 1.0036 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 12 | 7.082 ng/mL | Standard Deviation 15.2289 |
| Placebo | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 24 | 3.589 ng/mL | Standard Deviation 7.8108 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 33 | 18.542 ng/mL | Standard Deviation 3.9874 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 8 | 7.041 ng/mL | Standard Deviation 2.347 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 5 | 5.845 ng/mL | Standard Deviation 2.5725 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 4 | 5.070 ng/mL | Standard Deviation 0.9456 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 12 | 28.556 ng/mL | Standard Deviation 22.789 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 22 | 11.985 ng/mL | Standard Deviation 4.8243 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 15 | 14.067 ng/mL | Standard Deviation 7.1096 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 29 | 15.735 ng/mL | Standard Deviation 4.201 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 24 | 25.997 ng/mL | Standard Deviation 6.4384 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 5 | 14.856 ng/mL | Standard Deviation 7.6131 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 15 | 29.229 ng/mL | Standard Deviation 10.4929 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 8 | 19.906 ng/mL | Standard Deviation 9.8664 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 33 | 46.279 ng/mL | Standard Deviation 24.1457 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 22 | 36.811 ng/mL | Standard Deviation 26.856 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 24 | 83.262 ng/mL | Standard Deviation 64.2281 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 12 | 79.555 ng/mL | Standard Deviation 17.2126 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 4 | 12.606 ng/mL | Standard Deviation 5.7623 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 29 | 43.236 ng/mL | Standard Deviation 34.03 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 4 | 14.696 ng/mL | Standard Deviation 5.7926 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 5 | 17.308 ng/mL | Standard Deviation 7.5955 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 8 | 21.609 ng/mL | Standard Deviation 11.088 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 15 | 45.289 ng/mL | Standard Deviation 18.76 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 12 | 88.402 ng/mL | Standard Deviation 29.808 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 22 | 52.841 ng/mL | Standard Deviation 21.5542 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Week 24 | 101.406 ng/mL | Standard Deviation 45.4197 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 29 | 67.255 ng/mL | Standard Deviation 27.9376 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase | Day 33 | 77.142 ng/mL | Standard Deviation 32.4153 |
Secondary
Serum Concentration of Drug-Myostatin Complex, Whole Study
Participants in the Placebo arm received placebo during the double-blind (DB) period (up to Week 24) and received RO7239361 during the open label (OL) phase. PFS in table row title indicates when study drug was changed from vial to prefilled syringe (PFS). Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 252
Population: The pharmacodynamics (PD) data set included all available data from subjects for whom PD measurements were available at baseline and at least one other timepoint. Data are analyzed according to the arms in which participants started the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 12 | 7.082 ng/mL | Standard Deviation 15.2289 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 22 | 1.326 ng/mL | Standard Deviation 1.341 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 33 | 1.157 ng/mL | Standard Deviation 1.0036 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 48 (Week 24 OL) | 90.593 ng/mL | Standard Deviation 73.7102 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 15 | 0.613 ng/mL | Standard Deviation 0.2102 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 29 | 1.593 ng/mL | Standard Deviation 3.1007 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 84 (Week 60 OL) | 146.950 ng/mL | Standard Deviation 131.3706 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 36 (Week 12 OL) | 95.788 ng/mL | Standard Deviation 88.1521 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 25 (Week 1 OL) | 3.186 ng/mL | Standard Deviation 6.9734 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL: Day 1 PFS) | 64.400 ng/mL | Standard Deviation 0.5657 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 24 (end of DB period) | 3.589 ng/mL | Standard Deviation 7.8108 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 180 (Week 156 OL) | 45.933 ng/mL | Standard Deviation 28.3161 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 4 | 1.178 ng/mL | Standard Deviation 1.8833 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 8 | 4.924 ng/mL | Standard Deviation 12.9975 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 72 (Week 48 OL) | 92.086 ng/mL | Standard Deviation 68.5222 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL) | 95.529 ng/mL | Standard Deviation 48.0065 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL: Week 12 PFS) | 152.000 ng/mL | — |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 132 (Week 108 OL) | 95.811 ng/mL | Standard Deviation 48.144 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 252 (Week 228 OL) | 96.770 ng/mL | Standard Deviation 61.6084 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 168 (Week 144 OL: Day 1 PFS) | 105.700 ng/mL | Standard Deviation 54.5772 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 5 | 2.119 ng/mL | Standard Deviation 2.9826 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 108 (Week 84 OL) | 122.610 ng/mL | Standard Deviation 87.1911 |
| Placebo | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 60 (Week 36 OL) | 63.358 ng/mL | Standard Deviation 37.5591 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 144 (Week 120 OL) | 25.600 ng/mL | — |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL) | 30.186 ng/mL | Standard Deviation 7.0053 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 8 | 7.041 ng/mL | Standard Deviation 2.347 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 180 (Week 156 OL) | 25.589 ng/mL | Standard Deviation 12.2478 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 180 (Week 156 OL: Week 12 PFS) | 62.600 ng/mL | — |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 192 (Week 168 OL: Day 1 PFS) | 18.000 ng/mL | — |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 192 (Week 168 OL: Day 45 PFS) | 80.400 ng/mL | — |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 252 (Week 228 OL) | 52.680 ng/mL | Standard Deviation 20.8619 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 15 | 14.067 ng/mL | Standard Deviation 7.1096 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 22 | 11.985 ng/mL | Standard Deviation 4.8243 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 12 | 28.556 ng/mL | Standard Deviation 22.789 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 29 | 15.735 ng/mL | Standard Deviation 4.201 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 24 (end of DB period) | 25.997 ng/mL | Standard Deviation 6.4384 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 25 (Week 1 OL) | 31.963 ng/mL | Standard Deviation 8.024 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 4 | 5.070 ng/mL | Standard Deviation 0.9456 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 36 (Week 12 OL) | 22.584 ng/mL | Standard Deviation 8.6839 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 48 (Week 24 OL) | 27.461 ng/mL | Standard Deviation 7.2306 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 33 | 18.542 ng/mL | Standard Deviation 3.9874 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 60 (Week 36 OL) | 41.779 ng/mL | Standard Deviation 34.2407 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 72 (Week 48 OL) | 26.740 ng/mL | Standard Deviation 3.0256 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 5 | 5.845 ng/mL | Standard Deviation 2.5725 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 84 (Week 60 OL) | 27.110 ng/mL | Standard Deviation 3.2527 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 108 (Week 84 OL) | 36.014 ng/mL | Standard Deviation 10.9338 |
| Panel 1 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 132 (Week 108 OL) | 32.133 ng/mL | Standard Deviation 8.2848 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 132 (Week 108 OL) | 75.040 ng/mL | Standard Deviation 14.3015 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 15 | 29.229 ng/mL | Standard Deviation 10.4929 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 108 (Week 84 OL) | 66.020 ng/mL | Standard Deviation 7.2878 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 60 (Week 36 OL) | 89.712 ng/mL | Standard Deviation 38.9214 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 252 (Week 228 OL) | 87.900 ng/mL | Standard Deviation 38.5763 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 180 (Week 156 OL) | 103.300 ng/mL | Standard Deviation 16.5463 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 33 | 46.279 ng/mL | Standard Deviation 24.1457 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 72 (Week 48 OL) | 0.550 ng/mL | — |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 8 | 19.906 ng/mL | Standard Deviation 9.8664 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 24 (end of DB period) | 83.262 ng/mL | Standard Deviation 64.2281 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 12 | 79.555 ng/mL | Standard Deviation 17.2126 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 168 (Week 144 OL: Week 12 PFS) | 94.900 ng/mL | — |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 25 (Week 1 OL) | 77.926 ng/mL | Standard Deviation 56.9987 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL) | 69.325 ng/mL | Standard Deviation 17.7064 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 29 | 43.236 ng/mL | Standard Deviation 34.03 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 5 | 14.856 ng/mL | Standard Deviation 7.6131 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 36 (Week 12 OL) | 57.164 ng/mL | Standard Deviation 25.8284 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 4 | 12.606 ng/mL | Standard Deviation 5.7623 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 22 | 36.811 ng/mL | Standard Deviation 26.856 |
| Panel 2 RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 168 (Week 144 OL: Day 1 PFS) | 70.100 ng/mL | Standard Deviation 25.1213 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 252 (Week 228 OL) | 106.071 ng/mL | Standard Deviation 48.6434 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 29 | 67.255 ng/mL | Standard Deviation 27.9376 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 33 | 77.142 ng/mL | Standard Deviation 32.4153 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 4 | 14.696 ng/mL | Standard Deviation 5.7926 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 5 | 17.308 ng/mL | Standard Deviation 7.5955 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 8 | 21.609 ng/mL | Standard Deviation 11.088 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 15 | 45.289 ng/mL | Standard Deviation 18.76 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Day 22 | 52.841 ng/mL | Standard Deviation 21.5542 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 12 | 88.402 ng/mL | Standard Deviation 29.808 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 24 (end of DB period) | 101.406 ng/mL | Standard Deviation 45.4197 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 25 (Week 1 OL) | 102.211 ng/mL | Standard Deviation 40.2284 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 36 (Week 12 OL) | 101.234 ng/mL | Standard Deviation 42.0902 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 48 (Week 24 OL) | 103.657 ng/mL | Standard Deviation 45.8802 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 60 (Week 36 OL) | 67.163 ng/mL | Standard Deviation 8.4904 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 72 (Week 48 OL) | 102.025 ng/mL | Standard Deviation 31.4717 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 84 (Week 60 OL) | 117.719 ng/mL | Standard Deviation 41.1143 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 108 (Week 84 OL) | 114.806 ng/mL | Standard Deviation 32.7432 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 132 (Week 108 OL) | 107.378 ng/mL | Standard Deviation 37.8814 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL) | 108.100 ng/mL | Standard Deviation 35.5833 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 156 (Week 132 OL: Week 12 PFS) | 125.583 ng/mL | Standard Deviation 44.4144 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 168 (Week 144 OL: Day 1 PFS) | 122.633 ng/mL | Standard Deviation 91.2542 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Drug-Myostatin Complex, Whole Study | Week 168 (Week 144 OL: Day 8 PFS) | 119.000 ng/mL | — |
Secondary
Serum Concentration of Free Myostatin in the Double-Blind Phase
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 24
Population: The pharmacodynamics (PD) data set included all available data from subjects for whom PD measurements were available at baseline and at least one other timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 4 | 1356.6 pg/mL | Standard Deviation 641.27 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 29 | 1214.0 pg/mL | Standard Deviation 676.8 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 12 | 1366.5 pg/mL | Standard Deviation 631.28 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 22 | 1317.1 pg/mL | Standard Deviation 728.48 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 33 | 1141.4 pg/mL | Standard Deviation 606.99 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 8 | 1014.2 pg/mL | Standard Deviation 549.26 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 5 | 1438.2 pg/mL | Standard Deviation 809.18 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Baseline | 1405.1 pg/mL | Standard Deviation 809.57 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 15 | 1266.9 pg/mL | Standard Deviation 611.27 |
| Placebo | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 24 | 1194.0 pg/mL | Standard Deviation 599.59 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 5 | 446.6 pg/mL | Standard Deviation 108.81 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 22 | 382.4 pg/mL | Standard Deviation 82.58 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 24 | 297.1 pg/mL | Standard Deviation 74.62 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 4 | 421.4 pg/mL | Standard Deviation 70.6 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 12 | 307.8 pg/mL | Standard Deviation 97.84 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 29 | 372.3 pg/mL | Standard Deviation 79.97 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Baseline | 815.3 pg/mL | Standard Deviation 155.14 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 15 | 478.4 pg/mL | Standard Deviation 111.44 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 8 | 522.7 pg/mL | Standard Deviation 131.51 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 33 | 291.1 pg/mL | Standard Deviation 77.55 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 8 | 479.2 pg/mL | Standard Deviation 319.13 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 12 | 110.8 pg/mL | Standard Deviation 49.8 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 24 | 160.8 pg/mL | Standard Deviation 122.75 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 5 | 357.8 pg/mL | Standard Deviation 166.27 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Baseline | 1391.3 pg/mL | Standard Deviation 1084.97 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 33 | 115.7 pg/mL | Standard Deviation 84.49 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 15 | 280.8 pg/mL | Standard Deviation 148.53 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 22 | 284.8 pg/mL | Standard Deviation 324.16 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 29 | 179.0 pg/mL | Standard Deviation 137.39 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 4 | 321.3 pg/mL | Standard Deviation 165.91 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 24 | 23.4 pg/mL | Standard Deviation 25.34 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Baseline | 1121.8 pg/mL | Standard Deviation 526.45 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 4 | 58.3 pg/mL | Standard Deviation 33.2 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 5 | 66.1 pg/mL | Standard Deviation 39.07 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 8 | 206.8 pg/mL | Standard Deviation 419.21 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 15 | 54.8 pg/mL | Standard Deviation 61.85 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 22 | 35.3 pg/mL | Standard Deviation 51.45 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 29 | 24.8 pg/mL | Standard Deviation 27.24 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Day 33 | 24.3 pg/mL | Standard Deviation 30.64 |
| Panel 3 and Expansion RO7239361 | Serum Concentration of Free Myostatin in the Double-Blind Phase | Week 12 | 16.2 pg/mL | Standard Deviation 11.6 |
Secondary
Serum Concentration of Free Myostatin, Whole Study
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Baseline through Week 252
Population: The pharmacodynamics (PD) data set included all available data from subjects for whom PD measurements were available at baseline and at least one other timepoint. The Whole Study set reported here includes data from RO7239361-treated participants only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 4 | 421.4 pg/mL | Standard Deviation 70.6 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 72 | 326.8 pg/mL | Standard Deviation 151.29 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 12 | 394.0 pg/mL | Standard Deviation 179.78 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Baseline | 986.8 pg/mL | Standard Deviation 363.69 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 5 | 446.6 pg/mL | Standard Deviation 108.81 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 8 | 522.7 pg/mL | Standard Deviation 131.51 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 15 | 478.4 pg/mL | Standard Deviation 111.44 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 22 | 382.4 pg/mL | Standard Deviation 82.58 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 29 | 372.3 pg/mL | Standard Deviation 79.97 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Day 33 | 291.1 pg/mL | Standard Deviation 77.55 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 24 | 357.9 pg/mL | Standard Deviation 137.56 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 25 | 331.0 pg/mL | Standard Deviation 116.78 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 36 | 340.3 pg/mL | Standard Deviation 98.24 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 48 | 401.3 pg/mL | Standard Deviation 233.76 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 60 | 284.6 pg/mL | Standard Deviation 96.92 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 84 | 534.0 pg/mL | Standard Deviation 260.31 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 108 | 320.9 pg/mL | Standard Deviation 222.1 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 132 | 283.5 pg/mL | Standard Deviation 103.73 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 156 | 208.7 pg/mL | Standard Deviation 64.52 |
| Placebo | Serum Concentration of Free Myostatin, Whole Study | Week 180 | 212.5 pg/mL | Standard Deviation 146.37 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 156 | 48.9 pg/mL | Standard Deviation 22.42 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 29 | 179.0 pg/mL | Standard Deviation 137.39 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 108 | 84.4 pg/mL | Standard Deviation 61.19 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 33 | 115.7 pg/mL | Standard Deviation 84.49 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 12 | 115.0 pg/mL | Standard Deviation 62.23 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 24 | 139.1 pg/mL | Standard Deviation 111.63 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 25 | 154.5 pg/mL | Standard Deviation 115.21 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 132 | 71.0 pg/mL | Standard Deviation 40.02 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 36 | 81.4 pg/mL | Standard Deviation 36 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 48 | 79.0 pg/mL | Standard Deviation 37.85 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 144 | 95.2 pg/mL | — |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 60 | 90.4 pg/mL | Standard Deviation 39.3 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 72 | 132.0 pg/mL | Standard Deviation 146.37 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Baseline | 1358.4 pg/mL | Standard Deviation 964.47 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 4 | 321.3 pg/mL | Standard Deviation 165.91 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 5 | 357.8 pg/mL | Standard Deviation 166.27 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 252 | 20.0 pg/mL | — |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 8 | 479.2 pg/mL | Standard Deviation 319.13 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 84 | 74.2 pg/mL | Standard Deviation 13.58 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 15 | 280.8 pg/mL | Standard Deviation 148.53 |
| Panel 1 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 22 | 284.8 pg/mL | Standard Deviation 324.16 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 29 | 24.8 pg/mL | Standard Deviation 27.24 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 5 | 66.1 pg/mL | Standard Deviation 39.07 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 60 | 36.3 pg/mL | Standard Deviation 54.13 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 33 | 24.3 pg/mL | Standard Deviation 30.64 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 22 | 35.3 pg/mL | Standard Deviation 51.45 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 12 | 18.1 pg/mL | Standard Deviation 13.37 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 108 | 40.2 pg/mL | Standard Deviation 42.7 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 15 | 54.8 pg/mL | Standard Deviation 61.85 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 24 | 23.0 pg/mL | Standard Deviation 23.68 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 156 | 20.0 pg/mL | Standard Deviation 0 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Baseline | 1159.3 pg/mL | Standard Deviation 601.29 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 25 | 22.8 pg/mL | Standard Deviation 18.48 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 8 | 206.8 pg/mL | Standard Deviation 419.21 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Day 4 | 58.3 pg/mL | Standard Deviation 33.2 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 36 | 21.1 pg/mL | Standard Deviation 22.03 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 132 | 40.2 pg/mL | Standard Deviation 38.26 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 72 | 205.7 pg/mL | Standard Deviation 321.58 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 48 | 18.6 pg/mL | Standard Deviation 12.11 |
| Panel 2 RO7239361 | Serum Concentration of Free Myostatin, Whole Study | Week 84 | 115.6 pg/mL | Standard Deviation 146.44 |
Secondary
Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses.
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration. Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW. Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 6. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 28 hour |
| Panel 1 RO7239361 | Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 24 hour |
| Panel 2 RO7239361 | Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses. | 30 hour |
Secondary
Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose.
PK parameter estimates at steady state following approximately 12 weeks QW administration. Panel 3 = 50 mg QW Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight \>45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight \>45 kg) RO7239361.
Time frame: Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose. | 44 hour |