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

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)

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Reldesemtiv

Detailed 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) if the treating physician agrees to participate in the program.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • The Perron Institute
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital, Neurology Department
• Belgium
  • Leuven, Belgium, 3000
    • Uz Leuven Gasthuisberg Department of Neurology
• Canada
  • Quebec, Canada, G1J1Z4
    • CHU de Quebec-Universite Laval
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary - Heritage Medical Research Clinic
    • Edmonton, Alberta, Canada, T6G1Z1
      • University of Alberta
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 0C7
      • Stan Cassidy Centre for Rehabilitation
  • Ontario
    • Hamilton, Ontario, Canada, L8N4K1
      • McMaster University
    • Ottawa, Ontario, Canada, K1Y4E9
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montréal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K0M7
      • University of Saskatchewan
• Ireland
  • Dublin, Ireland, 9
    • RSCI Education and Research Center Beaumount Hospital
• Italy
  • Milan, Italy, 20149
    • IRCCS Istituto Auxologico Italiano Ospedale San Luca U.O. Neurologia e Stroke Unit
  • Torino, Italy, 10126
    • AOU Citta della Salute e della Scienza di Torino Universita degli Studi di Torino P.O. Mollinette - Dipartimento de Neuroscienze "Rita Levi Montalcini"
• Netherlands
  • Utrecht, Netherlands, 3584
    • UMC Utrecht Department of Neurology, ALS Center
• Spain
  • Madrid, Spain, 28016
    • Hospital San Rafael
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
• Sweden
  • Stockholm, Sweden, 113 61
    • Studieenheten, Akademiskt Specialistcentrum
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital & Medical Center - Barrow Neurological Institute
  • California
    • Orange, California, United States, 92868
      • University of California Irvine - ALS & Neuromuscular Center
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center - Forbes Norris MDA/ALS Research Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital Anschutz Outpatient Pavilion
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
  • Indiana
    • Indianapolis, Indiana, United States, 43202
      • Indiana University IU Health Neuroscience Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Outpatient Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Neurology Associates
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Institute for Human Performance
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health Neuroscience Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Dallas, Texas, United States, 75206
      • Texas Neurology, P.A.
  • Virginia
    • Henrico, Virginia, United States, 23233
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital - Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reldesemtiv 300 mg twice daily; Patients in this arm take 1 reldesemtiv 300 mg oral tablet twice a day for a 600 mg total daily dose (TDD). Participants who had been down titrated during the parent trail take 150 mg by mouth twice a day.	Drug: Reldesemtiv; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Safety and Tolerability	Incidence of treatment-emergent adverse events	Baseline to Week 34 (time the study was terminated prematurely)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Effect of Reldesemtiv on ALSFRS-R Functional Outcomes	Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total scores. ALSFRS-R total score range is from 0 to 48. A score of 48 reflects normal function.	Baseline to Week 32 (last timepoint before study was terminated prematurely)

Collaborators and Investigators

• Sponsor: Cytokinetics
• Investigators: Study Chair: Cytokinetics MD, Scientific Leadership at Cytokinetics

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2022
• Primary Completion (Actual): June 7, 2023
• Study Completion (Actual): June 7, 2023

Study Registration Dates

• First Submitted: June 16, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: July 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; CK-2127107; Reldesemtiv
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: CY 5032; 2021-004727-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No