The Drug Development Process > Phase II clinical trials with Reldesemtiv in Patients with Spinal Muscular Atrophy (SMA II-III)

presented in an oral presentation by John W. Day, MD, Ph.D., Professor of Neurology and Paediatrics (Genetics), Stanford University.

This hypothesis-generating study met its primary goal. It fulfills the effect and safety profile.

In collaboration with Astellas, Cytokinetics is developing reldesemtiv as a potential treatment for people with SMA and certain other debilitating diseases and conditions associated with skeletal muscle weakness and/or fatigue.

The study showed dose- and concentration-dependent increases in time to muscle fatigue as measured by changes from baseline in Six Minute Walk Distance (6MWD), a sub-maximal exercise test of aerobic capacity and endurance, and Maximal Expiratory Pressure (MEP), a measure of strength of respiratory muscles, after eight weeks of treatment with reldesemtiv.

The study enrolled 70 patients, 39 in Cohort 1 and 31 in Cohort 2. Ambulatory and non-ambulatory (Type II or Type III) patients 12 years of age and older were randomized 2:1, stratified by ambulatory ability, to receive reldesemtiv or placebo dosed twice daily for eight weeks. The first cohort of patients received 150 mg of reldesemtiv or placebo and the second cohort received 450 mg of reldesemtiv or placebo twice daily. Enrollment in this study was stopped short of the targeted 72 patients after blinded analyses of the variability around the changes from baseline of several efficacy measures demonstrated that the study had sufficient statistical power to detect clinically relevant differences versus placebo in efficacy endpoints with the 70 patients already enrolled.

The study, which examined two dose levels of reldesemtiv, 150 mg or 450 mg twice daily, demonstrated dose-dependent increases in 6MWD in ambulatory patients as measured at both post-baseline time points, week four and week eight. In the 150 mg twice daily group, the increase vs. placebo was 10.86 meters (p=0.2531) after four weeks of treatment with reldesemtiv and 7.72 meters (p=0.4684) after eight weeks of treatment. In the 450 mg twice daily group, the increase vs. placebo was 35.63 meters (p= 0.0037) at week four and 24.89 meters (p= 0.0584) at week eight. There was also a statistically significant correlation between Cmax, or peak concentration of reldesemtiv, and change from baseline in 6MWD, with a slope estimate of 9.53 meters/(µg/mL). (p=0.0086).

The study also showed increases vs. placebo in MEP. In the 150 mg twice daily group, the increase in MEP was 5.95 cm H2O (p=0.2276) after four weeks of treatment with reldesemtiv and 11.69 cm H2O (p=0.0378) after eight weeks of treatment. In the 450 mg twice daily group, the increase in MEP compared to placebo was 9.17 cm H2O (p=0.0855) after four weeks of treatment with reldesemtiv and 13.15 cm H2O (p=0.0298) after eight weeks of treatment. Other assessments in the study, including the Hammersmith Functional Motor Score – Extended, Revised Upper Limb Module, Timed Up-and-Go and Forced Vital Capacity did not demonstrate meaningful differences between reldesemtiv versus placebo

Adverse events were similar between groups receiving reldesemtiv and placebo. The most commonly observed adverse effects were headache, constipation and nausea. Four patients had serious adverse events reported that resulted in early termination of study drug treatment, all considered to be unrelated to reldesemtiv.

 

Cytokinetik presenterar nya resultat från den fas II kliniska studien av Reldesemtiv vid patienter med typ II, II IV , spinal muskelatrofi

Den kliniska studien utformades för att undersöka effekter av reldesemtiv, en snabbverkande skelettmuskel troponinaktivator i nästa generation (FSTA), på flera mått av muskelfunktion vid ambulatoriska och icke-ambulatoriska patienter med SMA.

Studien omfattade 70 patienter, 39 i kohort 1 och 31 i kohort 2. Patienter (typ III eller typ IV) och icke-ambulerande (typ II eller typ III) patienter i åldern 12 år och äldre randomiserades 2: 1 till Relativ eller få en placebo.

2 gånger dagligen i åtta veckor, stratifierad för poliklinisk eller icke-ambulatorisk status. Den första kohorten av patienter fick 150 mg av reldesemtiv eller placebo och den andra kohorten patienter fick 450 mg av reldesemtiv eller placebo.

Anmälan i denna studie avbröts efter de blinda variabilitetsanalyserna för grundlinjeskiftet av flera av effektåtgärderna, vilket visade att studien har tillräcklig statistisk effekt för att visa kliniskt relevanta skillnader i effekter slutpunkter jämfört med placebo.

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