Spinal Muscular Atrophy (SMA) MedDRA version: 20.1 Level: LLT Classification code 10051203 Term: Spinal muscular atrophy congenital System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: LLT Classification code 10041583 Term: Spinal muscular atrophy, unspecified System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10079413 Term: Spinal muscular atrophy type I System Organ Cl
Conditions
Interventions
Product Name: N/A
Product Code: RO7204239/F01-01
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: RO7204239
Other descriptive name: GYM329
Con
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Confirmed genetic diagnosis of 5q-autosomal recessive SMA • Part 2 only: available survival of motor neuron 2 gene copy number as previously determined by genetic testing and recorded in the participant's medical history • Symptomatic SMA disease, as per investigator’s clinical judgement • Age at screening: o Part 1 Cohorts A, B, and D: 5-10 years, inclusive o Part 1 Cohort C: 2-4 years, inclusive o Part 2: 2-25 years, inclusive • For Part 1 Cohorts A, B, and C and Part 2 only: Participants who are ambulant, where ambulant is defined as able to walk/run unassisted (i.e., without the use of assistive devices such as canes, walking sticks, crutches, walkers, person/hand held assistance, braces, orthoses, over the malleoli insoles or any other type of support) 10 meters in =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • For Part 1 Cohorts A and B only: Participants with contraindications for magnetic resonance imaging (MRI) scan, difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI • Part 1 Cohort D only: o Participants who are unable to adopt the correct position to ensure adequate quality of dual-energy X-ray absorptiometry (DXA) scan acquisition, as determined by the DXA scan technologist o Participants who have contractures at screening that would interfere with DXA scan acquisition or functional assessments, as confirmed by the DXA scan technologist and clinical evaluator o For participants able to take steps only: Able to walk unassisted 10 meters in 40°) at screening based on the participant's most recent X ray as performed per standard of care or scoliosis that would interfere with functional assessments, as confirmed by the clinical evaluator. An X-ray is not required if it is not clinically indicated o Participants who require invasive ventilation, tracheostomy, or the use of non-invasive ventilation during the daytime • For Part 2 only: Participants who recently initiated treatment (within 6 months prior to screening) with oral salbutamol or another ß2-adrenergic agonist taken orally • 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. For those who have completed a risdiplam study, or participated in a nusinersen or onasemnogene abeparvovec study, the same as described under inclusion criteria apply • Received previous administration of anti-myostatin therapies • Any history of cell therapy • Hospitalized for a pulmonary event within the last 2 months or planned hospitalization at the time of screening • Previous 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) • Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases considered to be clinically significant • Clinically significant electrocardiography (ECG) abnormalities at screening • Clinically significant abnormal findings at echocardiography at screening from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants • Any major illness within 1 month before screening • Received any multidrug and toxin extrusion1/2K (MATE) substrates within 2 weeks before screening • Hereditary fructose intolerance • Use of 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 • Clinically significant abnormalities in laboratory test results • Ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to the constituents of their formulations • 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 st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 Ambulant Cohorts A-C • Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam • Evaluation of pharmacokinetic (PK) parameters for RO7204239 when administered in combination with risdiplam • Evaluation of PK parameters for risdiplam when administered in combination with RO7204239 • Evaluation of the immune response to RO7204239 in combination with risdiplam • Evaluation of the pharmacodynamic (PD) effects of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam • Evaluation of RO7204239 PK/PD effects Part 2 • Evaluation of the efficacy of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam ;Secondary Objective: Part 2 • Evaluation of the efficacy and PD of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam • Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam • Evaluation of PK parameters for RO7204239 when administered in combination with risdiplam • Evaluation of PK parameters for risdiplam when administered in combination with RO7204239 • Evaluation of immune response to RO7204239 in combination with risdiplam ;Primary end point(s): Part 1 Ambulant Cohorts A-C 1. Incidence, severity, and causal relationship of adverse events (AEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) 2. Change from baseline in vital signs, physical findings, ECG, echocardiogram, relevant echocardiographic parameters and clinical laboratory results 3. Incidence of local and systemic injection reactions 4. Incidence of abnormal laboratory findings 5. Incidence of abnormal ECG parameters 6. Incidence of relevant echocardiographic parameter z scores >2 7. Incidence of abnormal vital signs 8. Serum concentration of RO7204239 at sp | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 2 1. Change from baseline in MFM Domain 1 + Domain 2 (D1 + D2) score at Week 72 of combination treatment (Study Week 80) 2. Change from baseline in MFM-32 item total score at Week 72 of combination treatment (Study Week 80) 3. Change from baseline in the time taken to rise from floor as measured by RHS Item 25 at Week 72 of combination treatment (Study Week 80) 4. Change from baseline in the time taken to walk/run 10 meters as measured by RHS Item 19 at Week 72 of combination treatment (Study Week 80) 5. Percent change from baseline in lean mass as assessed by full-body DXA scan (participants >=5 years) at Week 72 of combination treatment (Study Week 80) 6. Incidence, severity, and causal relationship of AEs, with severity determined according to NCI CTCAE v5.0 7. Change from baseline in vital signs, physical findings, ECG, echocardiogram, relevant echocardiographic parameters and clinical laboratory results 8. Incidence of local and systemic injection reactions 9. Incidence of abnormal laboratory findings 10. Incidence of abnormal ECG parameters 11. Incidence of relevant echocardiographic parameter z scores >2 12. Incidence of abnormal vital signs 13. Serum concentration of RO7204239 at specified timepoints 14. Cmax of RO7204239 at specified timepoints 15. AUC of RO7204239 at specified timepoints 16. Ctrough of RO7204239 at specified timepoints 17. Plasma concentration of risdiplam (and its metabolite M1) at specified timepoints 18. Cmax of risdiplam (and its metabolite M1) at specified timepoints 19. AUC of risdiplam (and its metabolite M1) at specified timepoints 20. Ctrough of risdiplam (and its metabolite M1) at specified timepoints 21. Prevalence of ADAs at baseline and incidence of ADAs during the study; Impact of ADA on PK, PD, safety and efficacy parameters ;Timepoint(s) of evaluation of this end point: 1-5. At week 72 6-16. Throughout the study at specified timepoints 17-20. At week 24 21. Throughout the study at specified time | — |
Countries
Belgium, France, Germany, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed