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

Spinal Muscular Atrophy Clinical Trial

— Jewelfish  

Official title:

An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Risdiplam (RO7034067) in Adult and Pediatric Patients With Spinal Muscular Atrophy

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
• 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
• 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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

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

External Links

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