A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7204239 in Combination with Risdiplam (RO7034067) in Ambulant Patients with Spinal Muscular Atrophy
- Conditions
- Spinal Muscular Atrophy (SMA)MedDRA version: 20.0Level: LLTClassification code 10079415Term: Spinal muscular atrophy type IIISystem Organ Class: 100000004850MedDRA version: 20.1Level: LLTClassification code 10051203Term: Spinal muscular atrophy congenitalSystem Organ Class: 100000004850MedDRA version: 20.1Level: LLTClassification code 10041583Term: Spinal muscular atrophy, unspecifiedSystem Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10079413Term: Spinal muscular atrophy type ISystem Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10079416Term: Spinal muscular atrophy type IISystem Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10079417Term: Spinal muscular atrophy infantile onsetSystem Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10079419Term: Spinal muscular atrophy pre-symptomaticSystem Organ Class: 100000004850MedDRA version: 20.0Level: LLTClassification code 10079418Term: Spinal muscular atrophy later onsetSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2021-003417-19-IT
- Lead Sponsor
- F. HOFFMANN - LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 180
• Participants who are 2 to 10 years of age inclusive at screening
• Participants who have a confirmed genetic diagnosis of 5q-autosomal recessive SMA
• Symptomatic SMA disease, as per investigator’s clinical judgement
• Participants who are ambulant, where ambulant is defined as able to walk/run 10 meters in <=30 seconds at screening
• Participants who have received previous SMA disease-modifying therapies may be included provided that
o Onasemnogene abeparvovec was received at least 90 days prior to screening. Participants should be tapered off steroids prior to receiving risdiplam. In addition, participants should have normal levels of liver function tests, coagulatory parameters, platelets, and troponin-I at 90 days after administration of onasemnogene abeparvovec or at least 1 month after tapering off corticosteroids, whichever comes later
o Nusinersen last dose was received at least 90 days prior to screening
o Risdiplam is switched to the investigational medicinal product (IMP) provided by the site
• Participants who have a legally authorized representative able to consent for the participant
• Participants who are able and willing to comply with the study protocol and to complete all study procedures, measurements, and visits
• For females of childbearing potential, or who will reach childbearing potential during the study: participants who have a negative blood pregnancy test at screening and agree to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for both 17 months after the final dose of RO7204239 and 28 days after the final dose of risdiplam
• For males who are expected to reach sexual maturity during the study: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm during the treatment period and for 28 days after the final dose of risdiplam and 4 months after the final dose of RO7204239
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
• Participants with 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, with the exception of those who have completed a risdiplam study, or participated in a nusinersen or onasemnogene abeparvovec study
• Participants who are receiving or have received previous administration of anti-myostatin therapies
• For Part 1 participants aged 5-10 years only: Participants who have contraindications for magnetic resonance imaging (MRI) scans, difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI
• Participants with any history of cell therapy
• Participants who have been hospitalized for a pulmonary event within the last 2 months or planned hospitalization at the time of screening
• Participants who have had surgery for scoliosis or hip fixation in the 6 months preceding screening or planned within the next 9 months (Part 1) or 21 months (Part 2)
• Participants who have unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases considered to be clinically significant
• Participants who have clinically significant electrocardiography (ECG) abnormalities at screening
• Participants with clinically significant abnormal findings at echocardiography at screening from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants
• Participants who have had any major illness within 1 month before screening
• Participants who have received any multidrug and toxin extrusion (MATE1/2K) substrates within 2 weeks before screening
• Participants who have used any of the following medications within 90 days prior to screening: riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, acetyl cholinesterase inhibitors, agents that could potentially increase or decrease muscle strength, and agents with known or presumed histone deacetylase (HDAC) inhibitory effect
• For Part 2 only: Participants who have recently initiated treatment (within <6 months prior to screening) with oral salbutamol or another ß2-adrenergic agonist taken orally is not allowed
• Participants who have clinically significant abnormalities in laboratory test results
• Participants who have ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to the constituents of their formulations
• Participants with concomitant disease or a condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in this study
• Participants who have a history of any malignancy
• Participants who have any clinically relevant history of anaphylactic reaction requiring inotropic support
• Participants who have any abnormal skin conditions, pigmentation or lesions in the area intended for subcutaneous (SC) injection (abdomen) and that would prevent visualization of potential injection site reactions to RO7204239
• Participants with immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening
• Female participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within either 17 months after the final
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method