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

Amyotrophic Lateral Sclerosis Clinical Trial

— COURAGE OLE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05442775
• Other study ID #: CY 5032
• Secondary ID: 2021-004727-33
• Status: Terminated
• Phase: Phase 3
• Start date: July 25, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: April 2023
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Reldesemtiv
Oral tablet

Locations

Country	Name	City	State
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Royal Brisbane and Women's Hospital, Neurology Department	Herston	Queensland
Australia	The Perron Institute	Nedlands
Belgium	Uz Leuven Gasthuisberg Department of Neurology	Leuven
Canada	University of Calgary - Heritage Medical Research Clinic	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Stan Cassidy Centre for Rehabilitation	Fredericton	New Brunswick
Canada	McMaster University	Hamilton	Ontario
Canada	Montreal Neurological Institute and Hospital	Montréal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHU de Quebec-Universite Laval	Quebec
Canada	University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Ireland	RSCI Education and Research Center Beaumount Hospital	Dublin
Italy	IRCCS Istituto Auxologico Italiano Ospedale San Luca U.O. Neurologia e Stroke Unit	Milan
Italy	AOU Citta della Salute e della Scienza di Torino Universita degli Studi di Torino P.O. Mollinette - Dipartimento de Neuroscienze "Rita Levi Montalcini"	Torino
Netherlands	UMC Utrecht Department of Neurology, ALS Center	Utrecht
Spain	Hospital San Rafael	Madrid
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Sweden	Studieenheten, Akademiskt Specialistcentrum	Stockholm
United States	Michigan Medicine	Ann Arbor	Michigan
United States	University of Colorado Hospital Anschutz Outpatient Pavilion	Aurora	Colorado
United States	Johns Hopkins Outpatient Center	Baltimore	Maryland
United States	Atrium Health Neuroscience Institute	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Texas Neurology, P.A.	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Virginia Commonwealth University	Henrico	Virginia
United States	Indiana University IU Health Neuroscience Center	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	University of Florida	Jacksonville	Florida
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Neurology Associates	Lincoln	Nebraska
United States	Froedtert Hospital - Department of Neurology	Milwaukee	Wisconsin
United States	Hospital for Special Surgery	New York	New York
United States	University of California Irvine - ALS & Neuromuscular Center	Orange	California
United States	St. Joseph's Hospital & Medical Center - Barrow Neurological Institute	Phoenix	Arizona
United States	California Pacific Medical Center - Forbes Norris MDA/ALS Research Center	San Francisco	California
United States	SUNY Upstate Medical University Institute for Human Performance	Syracuse	New York
United States	University of South Florida - Carol and Frank Morsani Center for Advanced Health Care	Tampa	Florida
United States	George Washington Medical Faculty Associates	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Ireland,  Italy,  Netherlands,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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