Clincosm LogoSign in Get a demo

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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03032172
Collaborator
(none)
174
Enrollment
24
Locations
1
Arm
93.8
Anticipated Duration (Months)
7.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
174 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 3, 2017
Anticipated Primary Completion Date :
Dec 27, 2024
Anticipated Study Completion Date :
Dec 27, 2024

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: Risdiplam
Risdiplam will be administered orally once daily.
Other Names:
  • RO7034067

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. 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]

    3. Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments [Baseline up to 5 years]

    4. Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments [Baseline up to 5 years]

    5. Tanner Staging Among all Participants Aged From 9 to 17 Years [Baseline up to 5 years]

    6. Mean Plasma Concentration of Risdiplam [Up to 2 years]

    7. Maximum Plasma Concentration (Cmax) of Risdiplam [Up to 2 years]

    8. Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam [Up to 2 years]

    9. Concentration of Risdiplam at the End of Dosing Interval (Ctrough) [Up to 2 years]

    10. Mean Plasma Concentration of Risdiplam Metabolite [Up to 2 years]

    11. Cmax of Risdiplam Metabolite [Up to 2 years]

    12. AUC of Risdiplam Metabolite [Up to 2 years]

    13. Ctrough of Risdiplam Metabolite [Up to 2 years]

    Secondary Outcome Measures

    1. SMN messenger Ribonucleic Acid (mRNA) Level in Blood [Up to 2 years]

    2. SMN Protein Levels in Blood [Up to 2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • With the exception of studies of olesoxime, AVXS-101, or nusinersen: 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

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford University Medical Center Palo Alto California United States 94304
    2 Nemours Children's Hospital Orlando Florida United States 32827
    3 Boston Childrens Hospital Boston Massachusetts United States 02115
    4 Columbia University Medical Center; The Neurological Institute of New York New York New York United States 10032
    5 UZ Gent Gent Belgium 9000
    6 UZ Leuven Gasthuisberg Leuven Belgium 3000
    7 Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique - L'ESCALE Bron France 69677
    8 Hopital Roger Salengro Lille France 59037
    9 CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie Montpellier France 34295
    10 Hôpital Necker-Enfants Malades; Service de neuropédiatrie Paris France 75015
    11 Hopital des Enfants; Unite de Neurologie Pediatrique Toulouse France 31059
    12 Universitätsklinikum Essen; Klinik für Kinderheilkunde I Essen Germany 45147
    13 Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen Freiburg Germany 79106
    14 IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative Roma Lazio Italy 00165
    15 Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile Roma Lazio Italy 00168
    16 IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative Genova Liguria Italy 16147
    17 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia Milano Lombardia Italy 20122
    18 UOSD Malattie Neurodegenerative Messina Sicilia Italy 98125
    19 UMC Utrecht; Polkliniek Neuromusculaire ziekten Utrecht Netherlands 3584 CX
    20 Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie Warszawa Poland 02-097
    21 Universitäts-Kinderspital (UKBB) Neuropädiatrie Basel Switzerland 4005
    22 Birmingham Heartlands Hospital Birmingham United Kingdom B9 5SS
    23 UCL Institute of Child Health & Great Ormond Street Hospital for Children London United Kingdom WC1N 1EH
    24 The Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne United Kingdom NE1 4LP

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT03032172
    Other Study ID Numbers:
    • BP39054
    • 2016-004184-39
    First Posted:
    Jan 26, 2017
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Muscular Atrophy
    Muscular Atrophy, Spinal
    Atrophy
    Risdiplam

    Study Results

    No Results Posted as of Aug 3, 2022