Duchenne Muscular Dystrophy
Conditions
Keywords
muscular dystrophy, Duchenne's Muscular Dystrophy, DMD
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of two different weekly doses of RO7239361 in ambulatory boys with Duchenne Muscular Dystrophy (DMD).
Interventions
DRUGRO7239361
Take RO7239361 subcutaneously on specified days over a 48 week blinded period
DRUGPlacebo for RO7239361
Take placebo subcutaneously on specified days over a 48 week blinded period
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with DMD by confirmed medical history and genetic testing * Able to walk without assistance * Minimum North Star Ambulatory Assessment score of 15 at screening * Able to walk up 4 stairs in 8 seconds or less * Weigh at least 15 kg (33 lbs) * Taking corticosteroids for DMD
Exclusion criteria
* Any behavior or mental issue that will affect the ability to complete the required study procedures * Previously or currently taking medications like androgens or human growth hormone * Use of a ventilator during the day * Unable to have blood samples collected or receive an injection under the skin * Concomitant or previous participation at any time in a gene therapy study Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline for the North Star Ambulatory Assessment (NSAA) Total Score | Baseline | The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. |
| Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 | Baseline, Week 48 | The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline for the Time to Stand From Supine | Baseline | The time required for a participant to stand from supine position. A longer time reflects a worse outcome. |
| Change From Baseline at Week 48 in Stand From Supine Velocity | Baseline, Week 48 | The time required for a participant to stand from supine position. A longer time reflects a worse outcome. A negative change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). |
| Baseline Time for 10 Meter Walk/Run | Baseline | The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome. |
| Change From Baseline at Week 48 in 10 M Walk/Run Velocity | Baseline, Week 48 | The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). |
| Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | Baseline | The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. |
| Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | Baseline, Week 48 | The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). |
| Baseline Time for 4 Stair Climb | Baseline | The time to complete the 4 stair climb was measured at baseline. |
| Baseline for the 6 Minute Walk Distance (6MWD) | Baseline | The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. |
| Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) | Baseline, Week 48 | The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). |
| Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Baseline, Week 48 | The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse at Week 48 as compared to baseline. |
| Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Baseline, Week 48 | Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement. |
| Number of Participants With Adverse Events (AEs) | During DB period (48 weeks) and Whole study (up to approximately 34 months) | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Number of Participants With AEs Leading to Discontinuation | During DB period (48 weeks) and Whole study (up to approximately 34 months) | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation. |
| Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline, Week 48 | Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement. |
| Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) | Baseline, Week 48 | 4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Italy, Japan, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up. | 56 |
| RO7239361 Low Dose Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up. | 55 |
| RO7239361 High Dose Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up. | 55 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Period | Administrative Reason by Sponsor | 24 | 25 | 21 |
| Double-blind Period | Death | 0 | 0 | 1 |
| Double-blind Period | Subject Request to Discontinue Study Treatment | 1 | 2 | 0 |
| Double-blind Period | Withdrawal by Subject | 2 | 2 | 1 |
| Open Label Period | Administrative Reason by Sponsor | 0 | 34 | 41 |
| Open Label Period | Subject Request to Discontinue Study Treatment | 0 | 1 | 0 |
| Open Label Period | Withdrawal by Subject | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | RO7239361 Low Dose | RO7239361 High Dose | Total | Placebo |
|---|---|---|---|---|
| Age, Continuous | 8.5 years STANDARD_DEVIATION 1.8 | 8.4 years STANDARD_DEVIATION 1.5 | 8.5 years STANDARD_DEVIATION 1.7 | 8.4 years STANDARD_DEVIATION 1.7 |
| Age, Customized Children (6-11 years) | 55 participants | 55 participants | 166 participants | 56 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 18 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 43 Participants | 127 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 6 Participants | 21 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 7 participants | 7 participants | 23 participants | 9 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 10 participants | 5 participants |
| Race/Ethnicity, Customized White | 45 participants | 45 participants | 132 participants | 42 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 55 Participants | 55 Participants | 166 Participants | 56 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 / 56 | 0 / 55 | 1 / 55 | 0 / 14 | 0 / 13 | 0 / 24 | 0 / 29 |
| other Total, other adverse events | 43 / 56 | 43 / 55 | 47 / 55 | 8 / 14 | 7 / 13 | 13 / 24 | 12 / 29 |
| serious Total, serious adverse events | 3 / 56 | 2 / 55 | 4 / 55 | 0 / 14 | 0 / 13 | 0 / 24 | 0 / 29 |
Outcome results
Primary
Baseline for the North Star Ambulatory Assessment (NSAA) Total Score
The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance.
Time frame: Baseline
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline for the North Star Ambulatory Assessment (NSAA) Total Score | 23.1 score on a scale | Standard Deviation 6.4 |
| RO7239361 Low Dose | Baseline for the North Star Ambulatory Assessment (NSAA) Total Score | 24.5 score on a scale | Standard Deviation 5.5 |
| RO7239361 High Dose | Baseline for the North Star Ambulatory Assessment (NSAA) Total Score | 22.7 score on a scale | Standard Deviation 6.7 |
Primary
Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48
The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=33.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 | -2.99 score on a scale | Standard Error 0.65 |
| RO7239361 Low Dose | Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 | -3.44 score on a scale | Standard Error 0.67 |
| RO7239361 High Dose | Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 | -2.41 score on a scale | Standard Error 0.64 |
95% CI: [-2.17, 1.27]
95% CI: [-1.1, 2.26]
Secondary
Baseline for the 6 Minute Walk Distance (6MWD)
The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome.
Time frame: Baseline
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline for the 6 Minute Walk Distance (6MWD) | 388.33 meters (m) | Standard Deviation 69.59 |
| RO7239361 Low Dose | Baseline for the 6 Minute Walk Distance (6MWD) | 399.73 meters (m) | Standard Deviation 68.35 |
| RO7239361 High Dose | Baseline for the 6 Minute Walk Distance (6MWD) | 370.73 meters (m) | Standard Deviation 93.35 |
Secondary
Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale
The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance.
Time frame: Baseline
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | 85.59 score on a scale | Standard Deviation 10.21 |
| RO7239361 Low Dose | Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | 86.54 score on a scale | Standard Deviation 9.52 |
| RO7239361 High Dose | Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | 84.47 score on a scale | Standard Deviation 14.76 |
Secondary
Baseline for the Time to Stand From Supine
The time required for a participant to stand from supine position. A longer time reflects a worse outcome.
Time frame: Baseline
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline for the Time to Stand From Supine | 6.28 secs | Standard Deviation 4.75 |
| RO7239361 Low Dose | Baseline for the Time to Stand From Supine | 6.15 secs | Standard Deviation 4.07 |
| RO7239361 High Dose | Baseline for the Time to Stand From Supine | 7.24 secs | Standard Deviation 9.22 |
Secondary
Baseline Time for 10 Meter Walk/Run
The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome.
Time frame: Baseline
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Time for 10 Meter Walk/Run | 5.38 secs | Standard Deviation 1.48 |
| RO7239361 Low Dose | Baseline Time for 10 Meter Walk/Run | 5.51 secs | Standard Deviation 1.68 |
| RO7239361 High Dose | Baseline Time for 10 Meter Walk/Run | 5.68 secs | Standard Deviation 2.3 |
Secondary
Baseline Time for 4 Stair Climb
The time to complete the 4 stair climb was measured at baseline.
Time frame: Baseline
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Time for 4 Stair Climb | 3.81 seconds (secs) | Standard Deviation 1.55 |
| RO7239361 Low Dose | Baseline Time for 4 Stair Climb | 3.85 seconds (secs) | Standard Deviation 1.61 |
| RO7239361 High Dose | Baseline Time for 4 Stair Climb | 3.92 seconds (secs) | Standard Deviation 1.91 |
Secondary
Change From Baseline at Week 48 in 10 M Walk/Run Velocity
The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=31.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in 10 M Walk/Run Velocity | -0.23 m/sec | Standard Error 0.06 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in 10 M Walk/Run Velocity | -0.14 m/sec | Standard Error 0.07 |
| RO7239361 High Dose | Change From Baseline at Week 48 in 10 M Walk/Run Velocity | -0.23 m/sec | Standard Error 0.06 |
95% CI: [-0.08, 0.27]
95% CI: [-0.17, 0.18]
Secondary
Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV)
4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=33.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) | -0.15 stairs/sec | Standard Error 0.07 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) | -0.15 stairs/sec | Standard Error 0.07 |
| RO7239361 High Dose | Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) | -0.07 stairs/sec | Standard Error 0.07 |
95% CI: [-0.21, 0.2]
95% CI: [-0.12, 0.27]
Secondary
Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD)
The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=29, Low Dose n=25, High Dose n=31.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) | -41.3 meters (m) | Standard Error 8.7 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) | -39.6 meters (m) | Standard Error 9 |
| RO7239361 High Dose | Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) | -30.0 meters (m) | Standard Error 8.7 |
95% CI: [-21.1, 24.6]
95% CI: [-11, 33.6]
Secondary
Change From Baseline at Week 48 in 95th Percentile Stride Velocity
Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement.
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Baseline | 1.69 m/sec | Standard Deviation 0.33 |
| Placebo | Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Change from Baseline at Week 48 | -0.25 m/sec | Standard Deviation 0.39 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Baseline | 1.54 m/sec | Standard Deviation 0.35 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Change from Baseline at Week 48 | -0.22 m/sec | Standard Deviation 0.22 |
| RO7239361 High Dose | Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Baseline | 1.57 m/sec | Standard Deviation 0.46 |
| RO7239361 High Dose | Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Change from Baseline at Week 48 | -0.28 m/sec | Standard Deviation 0.29 |
Secondary
Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale
The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=31, Low Dose n=29, High Dose n=34.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | -5.47 score on a scale | Standard Error 1.79 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | -7.47 score on a scale | Standard Error 1.83 |
| RO7239361 High Dose | Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | -4.51 score on a scale | Standard Error 1.77 |
95% CI: [-6.76, 2.77]
95% CI: [-3.71, 5.63]
Secondary
Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength
Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement.
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. Number analyzed is the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline: Knee Extenders | 5.58 kilogram (kg) | Standard Deviation 2.87 |
| Placebo | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Change from Baseline at Week 48: Knee Extenders | -1.19 kilogram (kg) | Standard Deviation 2.13 |
| Placebo | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline: Knee Flexors | 5.04 kilogram (kg) | Standard Deviation 2.58 |
| Placebo | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Change from Baseline at Week 48: Knee Flexors | 0.15 kilogram (kg) | Standard Deviation 2.24 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Change from Baseline at Week 48: Knee Flexors | 0.08 kilogram (kg) | Standard Deviation 2.53 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline: Knee Extenders | 6.25 kilogram (kg) | Standard Deviation 3.63 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline: Knee Flexors | 5.70 kilogram (kg) | Standard Deviation 3.08 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Change from Baseline at Week 48: Knee Extenders | -0.47 kilogram (kg) | Standard Deviation 2.43 |
| RO7239361 High Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Change from Baseline at Week 48: Knee Flexors | -0.13 kilogram (kg) | Standard Deviation 2.29 |
| RO7239361 High Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Change from Baseline at Week 48: Knee Extenders | -0.88 kilogram (kg) | Standard Deviation 2.97 |
| RO7239361 High Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline: Knee Flexors | 5.04 kilogram (kg) | Standard Deviation 2.72 |
| RO7239361 High Dose | Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Baseline: Knee Extenders | 5.76 kilogram (kg) | Standard Deviation 3.53 |
Secondary
Change From Baseline at Week 48 in Stand From Supine Velocity
The time required for a participant to stand from supine position. A longer time reflects a worse outcome. A negative change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM).
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=28, Low Dose n=28, High Dose n=32.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 48 in Stand From Supine Velocity | -0.05 1/sec | Standard Error 0.01 |
| RO7239361 Low Dose | Change From Baseline at Week 48 in Stand From Supine Velocity | -0.02 1/sec | Standard Error 0.01 |
| RO7239361 High Dose | Change From Baseline at Week 48 in Stand From Supine Velocity | -0.02 1/sec | Standard Error 0.01 |
95% CI: [0, 0.06]
95% CI: [0, 0.06]
Secondary
Number of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: During DB period (48 weeks) and Whole study (up to approximately 34 months)
Population: Safety population included all enrolled participants who received at least 1 dose of study therapy. Data are presented for the arms in the DB period as well as for all RO7239361-treated participants in the whole study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | Double-Blind Period | 46 participants |
| RO7239361 Low Dose | Number of Participants With Adverse Events (AEs) | Double-Blind Period | 48 participants |
| RO7239361 High Dose | Number of Participants With Adverse Events (AEs) | Double-Blind Period | 49 participants |
| RO7239361 Low Dose | Number of Participants With Adverse Events (AEs) | Whole Study | 57 participants |
| RO7239361 High Dose Whole Study | Number of Participants With Adverse Events (AEs) | Whole Study | 56 participants |
Secondary
Number of Participants With AEs Leading to Discontinuation
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation.
Time frame: During DB period (48 weeks) and Whole study (up to approximately 34 months)
Population: Safety population included all enrolled participants who received at least 1 dose of study therapy. Data are presented for the arms in the DB period as well as for all RO7239361-treated participants in the whole study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With AEs Leading to Discontinuation | Double-Blind Period | 0 participants |
| RO7239361 Low Dose | Number of Participants With AEs Leading to Discontinuation | Double-Blind Period | 0 participants |
| RO7239361 High Dose | Number of Participants With AEs Leading to Discontinuation | Double-Blind Period | 0 participants |
| RO7239361 Low Dose | Number of Participants With AEs Leading to Discontinuation | Whole Study | 0 participants |
| RO7239361 High Dose Whole Study | Number of Participants With AEs Leading to Discontinuation | Whole Study | 0 participants |
Secondary
Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48
The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse at Week 48 as compared to baseline.
Time frame: Baseline, Week 48
Population: Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment. Included in the analysis are only those subjects for whom an efficacy assessment was completed at Week 48.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Minimally worse | 16.7 percentage of participants |
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Much worse | 5.6 percentage of participants |
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Very much worse | 0 percentage of participants |
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Minimally improved | 13.9 percentage of participants |
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Very much improved | 0 percentage of participants |
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | No change | 58.3 percentage of participants |
| Placebo | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Much improved | 5.6 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Minimally worse | 18.9 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Minimally improved | 13.5 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Much worse | 10.8 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Much improved | 2.7 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | No change | 54.1 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Very much worse | 0 percentage of participants |
| RO7239361 Low Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Very much improved | 0 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Very much worse | 0 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Very much improved | 0 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Much improved | 3.2 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Minimally improved | 19.4 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | No change | 51.6 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Much worse | 3.2 percentage of participants |
| RO7239361 High Dose | Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | Minimally worse | 22.6 percentage of participants |