A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy

NCT ID: NCT03032172

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-03
• Study Completion Date: 2025-02-07

Brief Summary

This is a multi-center, exploratory, non-comparative, and open-label study to investigate the safety, tolerability, PK, and PK/PD relationship of risdiplam in adults, children and infants with Spinal Muscular Atrophy (SMA) previously enrolled in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101.

Conditions

Spinal Muscular Atrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Risdiplam

Participants will receive multiple doses of risdiplam orally once daily for 24 months. After 24-month treatment, participants will be offered the opportunity to enter the open-label extension (OLE) phase for 3 years.

Group Type: EXPERIMENTAL

Risdiplam

Intervention Type: DRUG

Risdiplam will be administered orally once daily.

Interventions

Risdiplam

Risdiplam will be administered orally once daily.

Intervention Type: DRUG

Other Intervention Names

RO7034067

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of 5q-autosomal recessive SMA
• Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previous treatment with any of the following: 1.) Nusinersen (defined as having received >= 4 doses of nusinersen, provided that the last dose was received >= 90 days prior to screening) or 2.) Olesoxime (provided that the last dose was received <= 12 months and >= 90 days prior to screening) or 3.) AVXS-101 (provided that the time of treatment was >= 12 months prior to screening)
• Adequately recovered from any acute illness at the time of screening and considered well enough to participate in the opinion of the Investigator
• For women of childbearing potential: negative blood pregnancy test at screening, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs for at least 28 days after the final dose of study drug
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
• For participants aged 2 years or younger at screening: 1.) Parent or caregiver of participant is willing to consider nasogastric, naso-jejunal or gastrostomy tube placement, as recommended by the Investigator, during the study to maintain safe hydration, nutrition and treatment delivery; 2.) Parent or caregiver of participant is willing to consider the use of non-invasive ventilation, as recommended by the Investigator during the study

Exclusion Criteria

• Inability to meet study requirements
• Concomitant participation in any investigational drug or device study
• 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 with the exception of studies of olesoxime, AVXS-101, or nusinersen
• Any history of gene or cell therapy, with the exception of AVXS-101
• Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
• Inadequate venous or capillary blood access for the study procedures, in the opinion of the Investigator
• For patients aged < 2 years, hospitalization for a pulmonary event within 2 months prior to screening and pulmonary function not fully recovered at the time of screening
• Lactating women
• Suspicion of regular consumption of drugs of abuse
• For adults and adolescents only, positive urine test for drugs of abuse or alcohol at screening or Day -1 visit
• Presence of clinically significant electrocardiogram (ECG) abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease
• History of malignancy if not considered cured
• For participants aged > 6 years, significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
• 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 for spinal muscular atrophy (within <6 weeks prior to enrollment) 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
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study
• Recent history (less than one year) of ophthalmological diseases
• Any prior use of an inhibitor or inducer of FMO1 or FMO3 taken within 2 weeks (or within 5 elimination half-lives, whichever is longer) prior to dosing

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Stanford University Medical Center

Palo Alto, California, United States

Nemours Children's Hospital

Orlando, Florida, United States

Boston Childrens Hospital

Boston, Massachusetts, United States

Columbia University Medical Center

New York, New York, United States

UZ Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Hopital Femme Mere Enfant

Bron, , France

Hopital Roger Salengro

Lille, , France

CHRU de Montpellier, Hopital Gui de Chauliac

Montpellier, , France

Hôpital Necker-Enfants Malades

Paris, , France

Hopital des Enfants

Toulouse, , France

Universitätsklinikum Essen

Essen, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

Policlinico Agostino Gemelli

Rome, Lazio, Italy

IRCCS Istituto Giannina Gaslini

Genoa, Liguria, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

UOSD Malattie Neurodegenerative

Messina, Sicily, Italy

UMC Utrecht

Utrecht, , Netherlands

Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

Warsaw, , Poland

Universitäts-Kinderspital (UKBB) Neuropädiatrie

Basel, , Switzerland

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

UCL Institute of Child Health & Great Ormond Street Hospital for Children

London, , United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

United States; Belgium; France; Germany; Italy; Netherlands; Poland; Switzerland; United Kingdom

References

Cleary Y, Kletzl H, Grimsey P, Heinig K, Ogungbenro K, Silber Baumann HE, Frey N, Aarons L, Galetin A, Gertz M. Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children. Clin Pharmacokinet. 2023 Jun;62(6):891-904. doi: 10.1007/s40262-023-01241-7. Epub 2023 May 6.

Reference Type: DERIVED

PMID: 37148485 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://roche-sma-clinicaltrials.com

roche-sma-clinicaltrials.com provides information about the Roche Jewelfish clinical trial NCT03032172 and molecule being investigated in SMA.

Other Identifiers

2016-004184-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506739-14-00

Identifier Type: CTIS

Identifier Source: secondary_id

BP39054

Identifier Type: -

Identifier Source: org_study_id