A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants (SUNFISH)
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ClinicalTrials.gov Identifier: NCT02908685 |
Recruitment Status :
Active, not recruiting
First Posted : September 21, 2016
Last Update Posted : July 22, 2020
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Condition or disease | Intervention/treatment | Phase |
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Muscular Atrophy, Spinal | Drug: Placebo Drug: Risdiplam | Phase 2 Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 231 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | A Two Part Seamless, Multi-Center Randomized, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy Patients |
Actual Study Start Date : | October 20, 2016 |
Actual Primary Completion Date : | September 6, 2019 |
Estimated Study Completion Date : | September 2, 2023 |

Arm | Intervention/treatment |
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Experimental: Part 1 Group A: Adolescents and Adults (Risdiplam)
Adolescent and adult participants aged 12-25 years will receive risdiplam for 12 weeks. Once 12-week treatment is completed and Part 2 dose is selected, participants will be switched to Part 2 dose and will be followed up in open-label extension (OLE) phase.
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Drug: Risdiplam
Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Other Name: RO7034067 |
Placebo Comparator: Part 1 Group A: Adolescents and Adults (Placebo)
Adolescent and adult participants aged 12-25 years will receive placebo matching to risdiplam for 12 weeks. Once 12-week treatment is completed and Part 2 dose is selected, participants will be switched to Part 2 dose and will be followed up in OLE phase.
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Drug: Placebo
Placebo will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube). Drug: Risdiplam Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Other Name: RO7034067 |
Placebo Comparator: Part 1 Group B: Children (Placebo)
Children aged 2-11 years will receive placebo matching to risdiplam for 12 weeks. Once 12-week treatment is completed and Part 2 dose is selected, participants will be switched to Part 2 dose and will be followed up in OLE phase.
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Drug: Placebo
Placebo will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube). Drug: Risdiplam Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Other Name: RO7034067 |
Experimental: Part 1 Group B: Children (Risdiplam)
Children aged 2-11 years will receive risdiplam for 12 weeks. Once 12-week treatment is completed and Part 2 dose is selected, participants will be switched to Part 2 dose and will be followed up in OLE phase.
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Drug: Risdiplam
Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Other Name: RO7034067 |
Placebo Comparator: Part 2: Placebo
Participants aged 2-25 years will receive placebo matching to risdiplam. After 12 months of treatment with placebo, participants will be switched to risdiplam and treatment will then continue until Month 24. After 24-month treatment, participants will be offered the opportunity to enter the OLE phase.
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Drug: Placebo
Placebo will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube). Drug: Risdiplam Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Other Name: RO7034067 |
Experimental: Part 2: Risdiplam
Participants aged 2-25 years will receive risdiplam at the dose selected based on the results from Part 1 of the study, for 24 months. After 24-month treatment, participants will be offered the opportunity to enter the OLE phase.
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Drug: Risdiplam
Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).
Other Name: RO7034067 |
- Part 2: Change from Baseline in the Total Motor Function Measure 32 (MFM-32) Score at Month 12 [ Time Frame: Baseline (Day -1) and Month 12 ]
- Part 1: Recommended Part 2 Dose of Risdiplam [ Time Frame: Minimum of 12 weeks ]
- Survival of Motor Neuron 2 (SMN2) Messenger Ribonucleic Acid (mRNA) Levels in Blood [ Time Frame: Part 2: Days -1, 1, 7, 28, 120, 246, 365, 729 ]
- Survival of Motor Neuron (SMN) Protein Levels in Blood [ Time Frame: Part 2: Days -1, 7, 28, 120, 246, 365, 729 ]
- Change from Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Percentage of Participants who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor Function Measure (MFM) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in the Best Sniff Nasal Inspiratory Pressure (SNIP) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in Forced Vital Capacity (FVC) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in the Peak Cough Flow (PCF) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in Maximal Inspiratory Pressure (MIP) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in Maximal Expiratory Pressure (MEP) at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Percentage of Participants who Experience at Least One Disease-Related Adverse Event [ Time Frame: Baseline up to Month 12 ]
- Part 1 and 2: Maximum Plasma Concentration (Cmax) of Risdiplam [ Time Frame: Part 1 and 2: 1, 2, 4, 6 hours post dose on Day 1; Pre-dose (Hour 0) on Days 7, 14, 56 (Part 2), 120, 246, 490, 729; pre-dose (Hour 0) and 1, 2, 4, 6 hours post dose on Days 28, 56 (Part 1), 365, 609 ]
- Part 1 and 2: Area Under the Curve (AUC) of Risdiplam [ Time Frame: Part 1 and 2: 1, 2, 4, 6 hours post dose on Day 1; Pre-dose (Hour 0) on Days 7, 14, 56 (Part 2), 120, 246, 490, 729; pre-dose (Hour 0) and 1, 2, 4, 6 hours post dose on Days 28, 56 (Part 1), 365, 609 ]
- Part 1 and 2: Concentration at the End of a Dosing Interval (Ctrough) of Risdiplam [ Time Frame: Part 1 and 2: Pre-dose (Hour 0) on Days 7, 14, 28, 56, 120, 246, 365, 490, 609, 729 ]
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 24 months ]
- Change from Baseline in the MFM Domain 1 (D1) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in the MFM Domain 2 (D2) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in the MFM Domain 3 (D3) Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Change from Baseline in the Total Combined Scores of MFM Domains 1 and 2 at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Percentage of Participants with Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline (Day-1), Day 120, Day 248, Day 386, Day 647, Day 729 ]
- Percentage of Participants by Clinical Global Impression of Change (CGI-C) Scale Ratings [ Time Frame: Month 12 ]
- Change from Baseline in SMA Independence Scale (SMAIS) Total Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]
- Percentage of Participants who Achieve an Improvement of at Least One Standard Error of Measurement on the Total MFM Score at Month 12 [ Time Frame: Baseline (Day-1) and Month 12 ]

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Ages Eligible for Study: | 2 Years to 25 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Confirmed diagnosis of 5q-autosomal recessive SMA
- Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation
- For Part 1: Type 2 or 3 SMA ambulant or non-ambulant
- For Part 2: 1) Type 2 or 3 SMA non-ambulant; 2) RULM entry item A greater than or equal to 2; 3) ability to sit independently as assessed by item 9 of the MFM
Exclusion Criteria:
- Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer
- Concomitant or previous administration of a SMN2-targeting antisense oligonucleotide, SMN2 splicing modifier or gene therapy either in a clinical study or as part of medical care
- Any history of cell therapy
- Hospitalization for a pulmonary event within the last 2 months or planned at time of screening
- Surgery for scoliosis or hip fixation in the one year preceding screening or planned within the next 18 months
- Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
- Presence of clinically significant electrocardiogram abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants as determined by the Investigator
- Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration
- Recently initiated treatment (within less than [<] 6 months prior to randomization) with oral salbutamol or another beta 2-adrenergic agonist taken orally
- Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed
- Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to Risdiplam or to the constituents of its formulation
- Recent history (less than one year) of ophthalmological diseases
- Participants requiring invasive ventilation or tracheostomy

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02908685

Study Director: | Clinical Trials | Hoffmann-La Roche |
Responsible Party: | Hoffmann-La Roche |
ClinicalTrials.gov Identifier: | NCT02908685 |
Other Study ID Numbers: |
BP39055 2016-000750-35 ( EudraCT Number ) |
First Posted: | September 21, 2016 Key Record Dates |
Last Update Posted: | July 22, 2020 |
Last Verified: | July 2020 |
Muscular Atrophy Muscular Atrophy, Spinal Atrophy Pathological Conditions, Anatomical Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases Spinal Cord Diseases |
Central Nervous System Diseases Motor Neuron Disease Neurodegenerative Diseases Neuromuscular Diseases Risdiplam Neuromuscular Agents Peripheral Nervous System Agents Physiological Effects of Drugs |