A Two-Part, Seamless, Multi-Center, Randomized, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Patients With Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA)

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), Part 1 Ambulant Cohorts A-C: 2. Change from baseline in vital signs, physical findings, ECG, echocardiogram, relevant echocardiographic parameters, and clinical laboratory results, Part 1 Ambulant Cohorts A-C: 3. Incidence of local and systemic injection reactions, Part 1 Ambulant Cohorts A-C: 4. Incidence of abnormal laboratory findings, Part 1 Ambulant Cohorts A-C: 5. Incidence of abnormal ECG parameters, Part 1 Ambulant Cohorts A-C: 6. Incidence of relevant echocardiographic parameter z scores > 2, Part 1 Ambulant Cohorts A-C: 7. Incidence of abnormal vital signs, Part 1 Ambulant Cohorts A-C: 8. Serum concentration of RO7204239 at specified timepoints, Part 1 Ambulant Cohorts A-C: 9. Maximum observed concentration (Cmax) of RO7204239 at specified timepoints, Part 1 Ambulant Cohorts A-C: 10. Area under the concentration-time curve (AUC) of RO7204239 at specified timepoints, Part 1 Ambulant Cohorts A-C: 11.Trough concentration (Ctrough) of RO7204239 at specified timepoints, Part 1 Ambulant Cohorts A-C: 12. Plasma concentration of risdiplam (and its metabolite M1) at specified timepoints, Part 1 Ambulant Cohorts A-C: 13. Cmax of risdiplam (and its metabolite M1) at specified timepoints, Part 1 Ambulant Cohorts A-C: 14. AUC of risdiplam (and its metabolite M1) at specified timepoints, Part 1 Ambulant Cohorts A-C: 15. Ctrough of risdiplam (and its metabolite M1) at specified timepoints, Part 1 Ambulant Cohorts A-C: 16. Prevalence of anti-drug antibodies (ADAs) against RO7204239 at baseline and incidence of ADAs during the study, Part 1 Ambulant Cohorts A-C: 17. Change from baseline in serum concentrations of total and free latent myostatin, and mature myostatin, Part 1 Ambulant Cohorts A-C: 18. Percentage change from baseline in the contractile area of skeletal muscle in the dominant thigh as assessed by MRI (participants >=5 years) at Week 24 of combination treatment, Part 1 Ambulant Cohorts A-C: 19. Percentage change from baseline in the contractile area of skeletal muscle in the dominant calf as assessed by MRI (participants >=5 years) at Week 24 of combination treatment, Part 1 Ambulant Cohorts A-C: 20. Relationship between PK and PD endpoints, ADA status, safety, or efficacy, Part 2: 21. Change from baseline in the Revised Hammersmith Scale (RHS) total score at Week 72 of combination treatment (Study Week 80)

Part 2: 1. Change from baseline in Motor Function Measure (MFM) Domain 1 + Domain 2 (D1 + D2) score at Week 72 of combination treatment (Study Week 80), Part 2: 2. Change from baseline in MFM-32 item total score at Week 72 of combination treatment (Study Week 80), Part 2: 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), Part 2: 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), Part 2: 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), Part 2: 6. Incidence, severity, and causal relationship of AEs, with severity determined according to NCI CTCAE v5.0, Part 2: 7. Change from baseline in vital signs, physical findings, ECG, echocardiogram, relevant echocardiographic parameters and clinical laboratory results, Part 2: 8. Incidence of local and systemic injection reactions, Part 2: 9. Incidence of abnormal laboratory findings, Part 2: 10. Incidence of abnormal ECG parameters, Part 2: 11. Incidence of relevant echocardiographic parameter z scores >2, Part 2: 12. Incidence of abnormal vital signs, Part 2: 13. Serum concentration of RO7204239 at specified timepoints, Part 2: 14. Cmax of RO7204239 at specified timepoints, Part 2: 15. AUC of RO7204239 at specified timepoints, Part 2: 16. Ctrough of RO7204239 at specified timepoints, Part 2: 17. Plasma concentration of risdiplam (and its metabolite M1) at specified timepoints, Part 2: 18. Cmax of risdiplam (and its metabolite M1) at specified timepoints, Part 2: 19. AUC of risdiplam (and its metabolite M1) at specified timepoints, Part 2: 20. Ctrough of risdiplam (and its metabolite M1) at specified timepoints, Part 2: 21. Prevalence of ADAs at baseline and incidence of ADAs during the study; Impact of ADA on PK, PD, safety and efficacy parameters

No related papers found yet.

None listed

Belgium, Croatia, France, Germany, Italy, Netherlands, Poland, Portugal, Spain