Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03032172
Other study ID # BP39054
Secondary ID 2016-004184-3920
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date March 3, 2017
Est. completion date December 27, 2024

Study information

Verified date June 2024
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 174
Est. completion date December 27, 2024
Est. primary completion date December 27, 2024
Accepts healthy volunteers No
Gender All
Age group 6 Months to 60 Years
Eligibility 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 Design


Intervention

Drug:
Risdiplam
Risdiplam will be administered orally once daily.

Locations

Country Name City State
Belgium UZ Gent Gent
Belgium UZ Leuven Gasthuisberg Leuven
France Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique ? L?ESCALE Bron
France Hopital Roger Salengro Lille
France CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie Montpellier
France Hôpital Necker-Enfants Malades; Service de neuropédiatrie Paris
France Hopital des Enfants; Unite de Neurologie Pediatrique Toulouse
Germany Universitätsklinikum Essen; Klinik für Kinderheilkunde I Essen
Germany Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen Freiburg
Italy IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative Genova Liguria
Italy UOSD Malattie Neurodegenerative Messina Sicilia
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia Milano Lombardia
Italy IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative Roma Lazio
Italy Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile Roma Lazio
Netherlands UMC Utrecht; Polkliniek Neuromusculaire ziekten Utrecht
Poland Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie Warszawa
Switzerland Universitäts-Kinderspital (UKBB) Neuropädiatrie Basel
United Kingdom 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 States Boston Childrens Hospital Boston Massachusetts
United States Columbia University Medical Center; The Neurological Institute of New York New York New York
United States Nemours Children's Hospital Orlando Florida
United States Stanford University Medical Center Palo Alto California

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Baseline up to 5 years
Primary 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) Baseline up to 5 years
Primary Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments Baseline up to 5 years
Primary Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments Baseline up to 5 years
Primary Tanner Staging Among all Participants Aged From 9 to 17 Years Baseline up to 5 years
Primary Mean Plasma Concentration of Risdiplam Up to 2 years
Primary Maximum Plasma Concentration (Cmax) of Risdiplam Up to 2 years
Primary Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam Up to 2 years
Primary Concentration of Risdiplam at the End of Dosing Interval (Ctrough) Up to 2 years
Primary Mean Plasma Concentration of Risdiplam Metabolite Up to 2 years
Primary Cmax of Risdiplam Metabolite Up to 2 years
Primary AUC of Risdiplam Metabolite Up to 2 years
Primary Ctrough of Risdiplam Metabolite Up to 2 years
Secondary SMN messenger Ribonucleic Acid (mRNA) Level in Blood Up to 2 years
Secondary SMN Protein Levels in Blood Up to 2 years
See also
  Status Clinical Trial Phase
Completed NCT04851873 - Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) Phase 3
Completed NCT03223051 - Development of a Space Exploration Assessment for Children With Spinal Muscular Atrophy N/A
Completed NCT04335942 - Characterization of the Postural Habits of Wheelchair Users Analysis of the Acceptability of International Recommendations in the Prevention of Pressure Sores Risk by Using a Connected Textile Sensor N/A
Recruiting NCT05794139 - Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy Phase 2
Not yet recruiting NCT06300996 - Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy - Upper Limb N/A
Completed NCT02003937 - Aerobic Training in Patients With Spinal Muscular Atrophy Type III N/A
Not yet recruiting NCT00961103 - Motor Development and Orthoses in Spinal Muscular Atrophy (SMA) N/A
Completed NCT00227266 - Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy Phase 2
Completed NCT00374075 - Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy Phase 1
Enrolling by invitation NCT05539456 - Reliability and Validity of the Turkish Version of the PedsQL 3.0 Neuromuscular Module for 2-to 4- Year-old
Recruiting NCT05779956 - Personalized Medicine for SMA: a Translational Project
Recruiting NCT03217578 - Neonatal Spinal Muscular Atrophy (SMA) Screening
Recruiting NCT03300869 - Natural History of Types 2 and 3 SMA in Taiwan
Completed NCT01703988 - An Open-label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Phase 1/Phase 2
Withdrawn NCT02235090 - Study of Feasibility to Reliably Measure Functional Abilities' Changes in Nonambulant Neuromuscular Patients Without Trial Site Visiting N/A
Completed NCT02123186 - Newborn Screening for Spinal Muscular Atrophy N/A
Completed NCT00756821 - A Pilot Study of Biomarkers for Spinal Muscular Atrophy N/A
Completed NCT00004771 - Phase II Study of Leuprolide and Testosterone for Men With Kennedy's Disease or Other Motor Neuron Disease Phase 2
Recruiting NCT05366465 - Quality of Life and Participation of the Adult With Spinal Muscular Atrophy in France
Recruiting NCT06310421 - Spinal Muscular Atrophy Neonatal Screening Program