A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)

Study Overview
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Brief Summary
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The purpose of this study is to assess the long-term safety and tolerability of reldesemtiv in patients with ALS who have successfully completed dosing in the Phase 3 clinical trial, CY 5031 (also known as COURAGE-ALS)

Detailed Description
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CY 5032 is an open-label extension (OLE) study of the selective fast skeletal muscle troponin activator, reldesemtiv, in patients with ALS who finished dosing (through Week 48) in CY 5031 (COURAGE-ALS). Approximately 400 patients from the sites that participated in CY 5031 are expected to be enrolled in the open-label extension, CY 5032. Following enrollment, patients will continue dosing with reldesemtiv, 300 mg twice a day for a 600 mg total daily dose (TDD) for a period of 48 weeks. At the end of 48 weeks, patients may transition to a reldesemtiv Managed Access Program (MAP) the treating physician agrees to participate in the program.

Official Title
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A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Reldesemtiv


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and willing to sign an ICF and willing to comply with all study procedures and restrictions for the duration specified in the Schedule of Activities. If non-written consent is given, a Legal Designee of the patient must sign the ICF form. Completed dosing in CY 5031 Exclusion Criteria: Has taken investigational study drug (other than reldesemtiv) prior to dosing, within 30 days or five half-lives of the prior agent, whichever is greater Presence on Day 1 of any medically significant cardiac, pulmonary, gastrointestinal, musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data. Use of a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days prior to first dose of reldesemtiv in CY 5032 or a strong CYP3A4 inducer within 14 days prior to first dose of reldesemtiv in CY 5032 Use of a medication that is an OCT1/OCT2 substrate within 7 days prior to first dose of reldesemtiv in CY 5032 Currently participating in another trial, managed access program, open label extension, early access program, or through the right to try act is receiving an investigational drug or received an investigational drug or device within 30 days (or 5 half-lives for drugs, whichever is longer) prior to Day 1. Patients also cannot be taking outside of a clinical trial certain investigational drugs (which includes drugs, supplements, and nutraceuticals) that are currently being studied or have been studied for the treatment of ALS.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reldesemtiv 300 mg twice daily<br>Patients in this arm take 1 reldesemtiv 300 mg oral tablet twice a day for a 600 mg total daily dose (TDD) | Drug: Reldesemtiv<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term safety and tolerability of reldesemtiv in patients with ALS | The incidence of adverse events (AEs) in the patient population | Baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031 | • Time to the first occurrence of respiratory insufficiency (defined as tracheostomy for any reason or the use of non-invasive ventilation (NIV) for ≥22 hours per day for ≥10 consecutive days) or death from date of randomization in CY 5031 through Week 48 of CY 5032 | Baseline to Week 48 | 
| Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031 | Time to the first hospitalization from Day 1 in CY 5031 through Week 48 of CY 5032 | Baseline to Week 48 | 
| Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031 | • Combined assessment of change in ALSFRS-R total score, time to onset of respiratory insufficiency, and survival time up to week 48. In this joint rank test each individual patient is ranked compared to all other patients based on survival time, time to onset of respiratory insufficiency, and changes from baseline to Week 24 in ALSFRS-R total score. Deaths have the worst rank (with earlier deaths being ranked worse than later deaths); patients with onset of respiratory insufficiency have the next worst rank; and the more favorable changes from baseline of CY 5031 through Week 48 of CY 5032 and from Week 24 of CY 5031 through Week 48 of CY 5032. | Baseline to Week 48 | 
| Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031 | • Changes in ALS Functional Rating Scale -Revised (ALSFRS-R) total score from baseline of CY 5031 through Week 48 of CY 5032 and from Week 24 of CY 5031 through Week 48 of CY 5032 | Baseline to Week 48 | 
| Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031 | • Slopes of the changes in ALSFRS-R total score from baseline of CY 5031 through Week 48 of CY 5032 and from Week 24 of CY 5031 through Week 48 of CY 5032 | Baseline to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv