Trial · NCT02908685
A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants
NCT02908685, Phase 2, Completed, Hoffmann-La Roche; results first posted 2021-06-15
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants. Trials, record NCT02908685. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02908685
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants
- NCT number
- NCT02908685
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 231 participants, actual
- Lead sponsor
- Hoffmann-La Roche
- Conditions
- Muscular Atrophy, Spinal
- Interventions
- Placebo, Risdiplam
- First posted
- 2016-09-21
- Last updated
- 2024-04-24
- Other registries' IDs
- eudract:2016-000750-35
- Results first posted
- 2021-06-15
Source ClinicalTrials.gov
Registered outcomes33
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg | Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017) | The Internal Monitoring Committee (IMC) was responsible for selecting the dose for Part 2 of the study (pivotal dose). An external Independent Data Monitoring Committee (iDMC) reviewed data from Part 1 and confirmed the dose-selection decision of the IMC. The dose for Part 2 selected by the IMC was a dose that: 1.Was judged to be safe and well-tolerated, based on all available safety data from Part 1 and as confirmed by the iDMC; 2. Resulted in an exposure at steady-state below the exposure cap (mean value) of AUC0-24h,ss 2000 ng\*h/mL (adjusted for free-fraction, if required); 3. Resulted in an SMN protein increase that was expected to be clinically relevant. |
| Primary | Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg | Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017) | The Internal Monitoring Committee (IMC) was responsible for selecting the dose for Part 2 of the study (pivotal dose). An external Independent Data Monitoring Committee (iDMC) reviewed data from Part 1 and confirmed the dose-selection decision of the IMC. The dose for Part 2 selected by the IMC was a dose that: 1.Was judged to be safe and well-tolerated, based on all available safety data from Part 1 and as confirmed by the iDMC; 2. Resulted in an exposure at steady-state below the exposure cap (mean value) of AUC0-24h,ss 2000 ng\*h/mL (adjusted for free-fraction, if required); 3. Resulted in an SMN protein increase that was expected to be clinically relevant. |
| Primary | Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12 | Baseline (Day-1) and Month 12 | The Motor Function Measure 32 (MFM32) is a scale constructed for use in neuromuscular disorders. It comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on primary efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12 | At Month 12 | The MFM32 comprises 32 items that evaluate physical function. The scoring of each task uses a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. A change in MFM32 total score of threshold \>/=3 represents marked improvement in this measure. Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12 | Baseline (Day-1) and Month 12 | The RULM is a 20 items scale that assesses the proximal and distal motor functions of the arm. There is an entry item and the remaining 18 items are scored on the 3 point scale of: 0: cannot complete task independently; 1: modified method but can complete task independently; 2: completes task without any assistance, and with 1 item scored on a 2 point scale of as a can/cannot score with 1 as the highest score. The RULM total score is the sum of 19 items scores with range of 0-37, and the entry item does not contribute to the total score. Higher scores indicate greater upper limb function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12 | Baseline (Day-1) and Month 12 | The HFMSE scale contains 33 items, which are scored on a 3-point Likert-type scale (0-2) and summed to derive the total score, with lower scores indicating greater impairment. The HFMSE contains a series of assessments designed to assess important functional abilities, including standing, transfers, ambulation, and proximal and axial function. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate greater motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Change From Baseline in Forced Vital Capacity (FVC) at Month 12 in Participants Aged 6-25 Years | Baseline (Day-1) and Month 12 | Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Forced vital capacity (FVC) is the total volume that can be exhaled after inhaling maximally. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Change From Baseline in the Caregiver-Reported SMA Independence Scale (SMAIS) Total Score at Month 12 | Baseline (Day-1) and Month 12 | The SMA Independence Scale (SMAIS) was developed specifically for SMA participants in order to assess function-related independence. The SMAIS contains 29 items, assessing the amount of assistance required from another individual to perform daily activities such as eating, or bathing. Each item is scored on a 0-4 scale (with an additional option to indicate that an item is non-applicable). The SMAIS total score ranging from 0-44 is obtained based on 22 items with each item on the 0-2 scale. Lower scores indicate greater dependence on another individual. The SMAIS was completed by participants aged 12 years or older and caregivers of participants aged 2-25 years. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Percentage of Participants Rated by Clinicians as Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12 | At Month 12 | The Clinical Global Impression of Change (CGI-C) is used to score a clinician's impression of a participant's change in global health. The CGI-C is a single item measure of change in global health, using seven response options: "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse". Participants considered as "improved" included responses of "very much improved, "much improved" and "minimally improved". Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
| Secondary | Part 2: Percentage of Participants Who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor Function Measure (MFM-32) Score at Month 12 | At Month 12 | The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. Higher scores indicate increased motor function. Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12. |
1 to 10 of 33Source ClinicalTrials.gov
See all 33 registered outcomesOutcomes33
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg | Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017) | All participants in Part 1. | milligram (mg) | NUMBER |
| PRIMARY | Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg | Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017) | All participants in Part 1. | milligram/kilogram (mg/kg) | NUMBER |
| PRIMARY | Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12 | Baseline (Day-1) and Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis. | Scores on a Scale | LEAST_SQUARES_MEAN |
| SECONDARY | Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12 | At Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis. Missing results at Month 12 are considered as non-responders. | Percentage of Participants | NUMBER |
| SECONDARY | Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12 | Baseline (Day-1) and Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing RULM total score at Baseline were not included in the analysis. | Scores on a Scale | LEAST_SQUARES_MEAN |
| SECONDARY | Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12 | Baseline (Day-1) and Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. | Scores on a Scale | LEAST_SQUARES_MEAN |
| SECONDARY | Part 2: Change From Baseline in Forced Vital Capacity (FVC) at Month 12 in Participants Aged 6-25 Years | Baseline (Day-1) and Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing FVC data at Baseline were not included in the analysis. | Percentage Predicted | LEAST_SQUARES_MEAN |
| SECONDARY | Part 2: Change From Baseline in the Caregiver-Reported SMA Independence Scale (SMAIS) Total Score at Month 12 | Baseline (Day-1) and Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing SMAIS total score at Baseline were not included in the analysis. | Scores on a Scale | LEAST_SQUARES_MEAN |
| SECONDARY | Part 2: Percentage of Participants Rated by Clinicians as Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12 | At Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Missing results at Month 12 are considered as non-responders. | Percentage of Participants | NUMBER |
| SECONDARY | Part 2: Percentage of Participants Who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor Function Measure (MFM-32) Score at Month 12 | At Month 12 | The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis. Missing results at Month 12 are considered as non-responders. | Percentage of Participants | NUMBER |
1 to 10 of 33Source ClinicalTrials.gov
See all 33 outcomesResults by group88
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg | Part 1: All Risdiplam | 5 | milligram (mg) | ||
| Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg | Part 1: All Risdiplam | 0.25 | milligram/kilogram (mg/kg) | ||
| Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12 | Part 2: Risdiplam | 1.36 | 95% Confidence Interval 0.61 to 2.11 | Scores on a Scale | |
| Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12 | Part 2: Placebo | -0.19 | 95% Confidence Interval -1.22 to 0.84 | Scores on a Scale | |
| Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12 | Part 2: Risdiplam | 38.3 | 95% Confidence Interval 28.94 to 47.58 | Percentage of Participants | |
| Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12 | Part 2: Placebo | 23.7 | 95% Confidence Interval 12.03 to 35.43 | Percentage of Participants | |
| Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12 | Part 2: Risdiplam | 1.61 | 95% Confidence Interval 1.00 to 2.22 | Scores on a Scale | |
| Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12 | Part 2: Placebo | 0.02 | 95% Confidence Interval -0.83 to 0.87 | Scores on a Scale | |
| Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12 | Part 2: Risdiplam | 0.95 | 95% Confidence Interval 0.29 to 1.61 | Scores on a Scale | |
| Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12 | Part 2: Placebo | 0.37 | 95% Confidence Interval -0.54 to 1.28 | Scores on a Scale |
1 to 10 of 88Source ClinicalTrials.gov
See all 88 results by groupParticipant flow210
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Part 1 Placebo-Controlled | STARTED | Part 1 Group A Cohort 1: Adolescents and Adults (3 mg Risdiplam) | 7 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group A Cohort 2: Adolescents and Adults (5 mg Risdiplam) | 7 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group A Cohort 1: Adolescents and Adults (Placebo) | 3 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group A Cohort 2: Adolescents and Adults (Placebo) | 3 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group B Cohort 1: Children (0.02 mg/kg Risdiplam) | 7 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group B Cohort 2: Children (0.05 mg/kg Risdiplam) | 7 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group B Cohort 3: Children (0.25 mg/kg Risdiplam) | 7 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group B Cohort 1: Children (Placebo) | 3 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group B Cohort 2: Children (Placebo) | 4 | |
| Part 1 Placebo-Controlled | STARTED | Part 1 Group B Cohort 3: Children (Placebo) | 3 |
1 to 10 of 210Source ClinicalTrials.gov
See all 210 participant flowAdverse events3,210
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group A: Adolescents and Adults (3 mg Risdiplam) | 0 | 10 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group A: Adolescents and Adults (5 mg Risdiplam) | 0 | 10 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled) | 0 | 6 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group B: Children (0.02 mg/kg Risdiplam) | 0 | 7 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group B: Children (0.05 mg/kg Risdiplam) | 0 | 14 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group B: Children (0.15 mg/kg Risdiplam) | 0 | 21 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group B: Children (0.25 mg/kg Risdiplam) | 0 | 7 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group B: Children (Placebo-Control Period Pooled) | 0 | 10 | 0 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group A: OLE | 1 | 20 | 1 |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Part 1 Group B: OLE | 0 | 31 | 0 |
1 to 10 of 3,210Source ClinicalTrials.gov
See all 3,210 adverse eventsAdverse event totals45
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Part 1 Group A: Adolescents and Adults (3 mg Risdiplam) | 0 | 10 |
| Total, all-cause mortality | Part 1 Group A: Adolescents and Adults (5 mg Risdiplam) | 0 | 10 |
| Total, all-cause mortality | Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled) | 0 | 6 |
| Total, all-cause mortality | Part 1 Group B: Children (0.02 mg/kg Risdiplam) | 0 | 7 |
| Total, all-cause mortality | Part 1 Group B: Children (0.05 mg/kg Risdiplam) | 0 | 14 |
| Total, all-cause mortality | Part 1 Group B: Children (0.15 mg/kg Risdiplam) | 0 | 21 |
| Total, all-cause mortality | Part 1 Group B: Children (0.25 mg/kg Risdiplam) | 0 | 7 |
| Total, all-cause mortality | Part 1 Group B: Children (Placebo-Control Period Pooled) | 0 | 10 |
| Total, all-cause mortality | Part 1 Group A: OLE | 0 | 20 |
| Total, all-cause mortality | Part 1 Group B: OLE | 0 | 31 |
1 to 10 of 45Source ClinicalTrials.gov
See all 45 adverse event totalsPapers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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GET https://conductscience.org/api/trials/v1/NCT02908685/registered?page=2