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

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ClinicalTrials.gov Identifier: NCT03032172
Recruitment Status : Recruiting
First Posted : January 26, 2017
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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 or olesoxime.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Drug: Risdiplam Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
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 RO7034067 in Adult and Pediatric Patients With Spinal Muscular Atrophy
Actual Study Start Date : March 3, 2017
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2020


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 OLE phase.
Drug: Risdiplam
Risdiplam will be administered orally once daily.
Other Name: RO7034067




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 [ Time Frame: 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) [ Time Frame: Aged 6 to 60 Years: Screening, Day-1, Day 182, 364, 546, 728, at extension phase and follow-up visit 1 (Week 112) ]
  3. Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments [ Time Frame: Baseline up to 5 years ]
  4. Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments [ Time Frame: Baseline up to 5 years ]
  5. Tanner Staging Among all Participants Aged From 9 to 17 Years [ Time Frame: Baseline up to 5 years ]
  6. Mean Plasma Concentration of RO7034067 [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  7. Maximum Plasma Concentration (Cmax) of RO7034067 [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  8. Area Under the Plasma Concentration Versus Curve (AUC) of RO7034067 [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  9. Concentration of RO7034067 at the End of Dosing Interval (Ctrough) [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  10. Mean Plasma Concentration of RO7034067 Metabolite [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  11. Cmax of RO7034067 Metabolite [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  12. AUC of RO7034067 Metabolite [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]
  13. Ctrough of RO7034067 Metabolite [ Time Frame: Aged 2-60 years: at pre-defined intervals up to Week 104; aged 6 months to 2 years: at pre-defined intervals up to extension phase (up to 4 years after the last patient is enrolled in the study) ]

Secondary Outcome Measures :
  1. SMN messenger Ribonucleic Acid (mRNA) Level in Blood [ Time Frame: Aged 2 to 60 Years: Days -1, 1, 28, 91, 183, 365, 729, at early withdrawal, and at follow-up visit 1; Patients Aged 6 Months to <2 Years: Day 1, 28, 182, 364 and 728 and at early withdrawal ]
  2. SMN Protein Levels in Blood [ Time Frame: Aged 2 to 60 Years: Day -1, Day 28, 91, 183, 365, 729, at early withdrawal, and at follow-up visit 1; Patients Aged 6 Months to <2 Years: Day 1, 28, 182, 364 and 728 and at early withdrawal ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  • 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 men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
  • For patients aged 2 years or younger at screening: 1.) Parent or caregiver of patient is willing to consider nasogastric, naso-jejunal or gastrostomy tube placement, as recommended by the Investigator, during the study (if not already in place at the time of screening) to maintain safe hydration, nutrition and treatment delivery. 2.) Parent or caregiver of patient is willing to consider the use of non-invasive ventilation, as recommended by the Investigator during the study (if not already in place at the time of screening).

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, with the exception of studies with olesoxime or nusinersen, within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer
  • Any history of gene or cell therapy
  • 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
  • For patients aged > 6 years, significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the 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 RO7034067 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 that would interfere with the conduct of the study as assessed by an ophthalmologist. Participants in whom Organic Cation Transporter or Spectral Domain-Optical Coherence Tomography (SD-OCT) measurement of sufficient quality cannot be obtained at screening will not be enrolled

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03032172


Contacts
Contact: Reference Study ID Number: BP39054 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, New York
Columbia University Medical Center; The Neurological Institute of New York Recruiting
New York, New York, United States, 10032
Italy
Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile Recruiting
Roma, Lazio, Italy, 00168
Switzerland
Universitäts-Kinderspitalbeider Basel_Abteilung für Neuro- und Entwicklungspädiatrie Recruiting
Basel, Switzerland, 4005
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Additional Information:
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03032172     History of Changes
Other Study ID Numbers: BP39054
2016-004184-39 ( EudraCT Number )
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Cord Diseases
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases