- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03032172
A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy (Jewelfish)
March 14, 2024 updated by: Hoffmann-La Roche
An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Risdiplam (RO7034067) in Adult and Pediatric Patients With Spinal Muscular Atrophy
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
174
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Gent, Belgium, 9000
- UZ Gent
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Leuven, Belgium, 3000
- UZ Leuven Gasthuisberg
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Bron, France, 69677
- Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique ? L?ESCALE
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Lille, France, 59037
- Hôpital Roger Salengro
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Montpellier, France, 34295
- CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie
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Paris, France, 75015
- Hôpital Necker-Enfants Malades; Service de neuropédiatrie
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Toulouse, France, 31059
- Hopital des Enfants; Unite de Neurologie Pediatrique
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Essen, Germany, 45147
- Universitätsklinikum Essen; Klinik für Kinderheilkunde I
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Freiburg, Germany, 79106
- Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen
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Lazio
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Roma, Lazio, Italy, 00165
- IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative
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Roma, Lazio, Italy, 00168
- Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile
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Liguria
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Genova, Liguria, Italy, 16147
- IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative
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Lombardia
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Milano, Lombardia, Italy, 20122
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia
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Sicilia
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Messina, Sicilia, Italy, 98125
- UOSD Malattie Neurodegenerative
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Utrecht, Netherlands, 3584 CX
- UMC Utrecht; Polkliniek Neuromusculaire ziekten
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Warszawa, Poland, 02-097
- Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
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Basel, Switzerland, 4005
- Universitäts-Kinderspital (UKBB) Neuropädiatrie
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Birmingham, United Kingdom, B9 5SS
- Birmingham Heartlands Hospital
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London, United Kingdom, WC1N 1EH
- UCL Institute of Child Health & Great Ormond Street Hospital for Children
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Newcastle upon Tyne, United Kingdom, NE7 7DN
- The Newcastle upon Tyne Hospitals NHS Foundation Trust
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California
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Palo Alto, California, United States, 94304
- Stanford University Medical Center
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Florida
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Orlando, Florida, United States, 32827
- Nemours Children's Hospital
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Boston Childrens Hospital
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center; The Neurological Institute of New York
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 months to 60 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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.
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Risdiplam will be administered orally once daily.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Scale, V 4.0
Time Frame: Baseline up to 5 years
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Baseline up to 5 years
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Percentage of Participants With Emergence or Worsening of Symptoms As Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) (Adult Version for Adults and Adolescents, Pediatric Version for Patients Aged 6-11 Years)
Time Frame: Baseline up to 5 years
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Baseline up to 5 years
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Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments
Time Frame: Baseline up to 5 years
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Baseline up to 5 years
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Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments
Time Frame: Baseline up to 5 years
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Baseline up to 5 years
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Tanner Staging Among all Participants Aged From 9 to 17 Years
Time Frame: Baseline up to 5 years
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Baseline up to 5 years
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Mean Plasma Concentration of Risdiplam
Time Frame: Up to 2 years
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Up to 2 years
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Maximum Plasma Concentration (Cmax) of Risdiplam
Time Frame: Up to 2 years
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Up to 2 years
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Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam
Time Frame: Up to 2 years
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Up to 2 years
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Concentration of Risdiplam at the End of Dosing Interval (Ctrough)
Time Frame: Up to 2 years
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Up to 2 years
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Mean Plasma Concentration of Risdiplam Metabolite
Time Frame: Up to 2 years
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Up to 2 years
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Cmax of Risdiplam Metabolite
Time Frame: Up to 2 years
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Up to 2 years
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AUC of Risdiplam Metabolite
Time Frame: Up to 2 years
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Up to 2 years
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Ctrough of Risdiplam Metabolite
Time Frame: Up to 2 years
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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SMN messenger Ribonucleic Acid (mRNA) Level in Blood
Time Frame: Up to 2 years
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Up to 2 years
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SMN Protein Levels in Blood
Time Frame: Up to 2 years
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Up to 2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 3, 2017
Primary Completion (Estimated)
December 27, 2024
Study Completion (Estimated)
December 27, 2024
Study Registration Dates
First Submitted
January 24, 2017
First Submitted That Met QC Criteria
January 24, 2017
First Posted (Estimated)
January 26, 2017
Study Record Updates
Last Update Posted (Actual)
March 18, 2024
Last Update Submitted That Met QC Criteria
March 14, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neuromuscular Manifestations
- Pathological Conditions, Anatomical
- Spinal Cord Diseases
- Motor Neuron Disease
- Muscular Atrophy
- Atrophy
- Muscular Atrophy, Spinal
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Neuromuscular Agents
- Risdiplam
Other Study ID Numbers
- BP39054
- 2016-004184-39 (EudraCT Number)
- 2023-506739-14-00 (Registry Identifier: EU CT number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org).
Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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