A study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of Risdiplam (RO7034067) in type 2 and 3 spinal muscular atrophy patients

Phase 1

• Conditions: Spinal Muscular Atrophy (SMA) Type 2 and 3; MedDRA version: 20.1Level: PTClassification code 10041582Term: Spinal muscular atrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2016-000750-35-GB
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-06-23
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 231

Inclusion Criteria

- Males and females 2 to 25 years of age inclusive
- For Part 1: Type 2 or 3 SMA ambulant or non-ambulant. For Part 2: Type 2 or 3 SMA non-ambulant.
Non-ambulant is defined as not having the ability to walk unassisted for 10 m or more
- Confirmed diagnosis of 5q-autosomal recessive SMA
- Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation

Are the trial subjects under 18? yes
Number of subjects for this age range: 185
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Concomitant or 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
- Concomitant or previous administration of a SMN2 targeting antisense oligonucleotide, SMN2 splicing modifier or gene therapy either in a clinical study or as part of medical care.
- Any history of cell therapy
- Hospitalization for a pulmonary event within the last 2 months or planned at time of screening
- Surgery for scoliosis or hip fixation in the one year preceding screening or planned within the next 18 months
- Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
- Presence of clinically significant ECG abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease indicating a safety risk for patients as determined by the Investigator
- History of malignancy if not considered cured
- Significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the C-SSRS (>6 years of age)
- 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
- Any Organic cation transporter (OCT)-2 and multidrug and toxin extrusion (MATE) substrates within 2 weeks before dosing
- Use of the following medications within 90 days prior to randomization: riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, agents anticipated to increase or decrease muscle strength, agents with known or presumed histone deacetylase (HDAC) inhibitory effect, and medications with known phototoxicity liabilities
- Recently initiated treatment (within < 6 months prior to randomization) with oral salbutamol or another 2-adrenergic agonist taken orally
- Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed.
- Clinically significant abnormalities in laboratory test results
- Donation or loss of blood >= 10% of blood volume within three months prior to screening
- Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to risdiplam or to the constituents of its formulation
- Recent history (less than one year) of ophthalmological diseases
- Patients requiring invasive ventilation or tracheostomy
- Any inhibitor or inducer of FMO1 or FMO3 taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified