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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Reldesemtiv
Sponsored by
Cytokinetics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St. Joseph's Hospital & Medical Center - Barrow Neurological Institute
  • University of California Irvine - ALS & Neuromuscular Center
  • California Pacific Medical Center - Forbes Norris MDA/ALS Research Center
  • University of Colorado Hospital Anschutz Outpatient Pavilion
  • George Washington Medical Faculty Associates
  • University of Florida
  • Mayo Clinic Jacksonville
  • University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
  • Indiana University IU Health Neuroscience Center
  • The University of Kansas Medical Center
  • Johns Hopkins Outpatient Center
  • Michigan Medicine
  • Henry Ford Hospital
  • Neurology Associates
  • Hospital for Special Surgery
  • SUNY Upstate Medical University Institute for Human Performance
  • Atrium Health Neuroscience Institute
  • Cleveland Clinic
  • Texas Neurology, P.A.
  • Virginia Commonwealth University
  • Froedtert Hospital - Department of Neurology
  • Concord Repatriation General Hospital
  • Royal Brisbane and Women's Hospital, Neurology Department
  • The Perron Institute
  • Uz Leuven Gasthuisberg Department of Neurology
  • University of Calgary - Heritage Medical Research Clinic
  • University of Alberta
  • Stan Cassidy Centre for Rehabilitation
  • McMaster University
  • Ottawa Hospital Research Institute
  • Sunnybrook Health Sciences Centre
  • Montreal Neurological Institute and Hospital
  • University of Saskatchewan
  • CHU de Quebec-Universite Laval
  • RSCI Education and Research Center Beaumount Hospital
  • IRCCS Istituto Auxologico Italiano Ospedale San Luca U.O. Neurologia e Stroke Unit
  • AOU Citta della Salute e della Scienza di Torino Universita degli Studi di Torino P.O. Mollinette - Dipartimento de Neuroscienze "Rita Levi Montalcini"
  • UMC Utrecht Department of Neurology, ALS Center
  • Hospital San Rafael
  • Hospital Universitario y Politecnico La Fe
  • Studieenheten, Akademiskt Specialistcentrum

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Reldesemtiv 300 mg twice daily

Arm Description

Patients in this arm take 1 reldesemtiv 300 mg oral tablet twice a day for a 600 mg total daily dose (TDD)

Outcomes

Primary Outcome Measures

Long-term safety and tolerability of reldesemtiv in patients with ALS
The incidence of adverse events (AEs) in the patient population

Secondary Outcome Measures

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
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
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.
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
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

Full Information

First Posted
June 16, 2022
Last Updated
April 12, 2023
Sponsor
Cytokinetics
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1. Study Identification

Unique Protocol Identification Number
NCT05442775
Brief Title
A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
Acronym
COURAGE OLE
Official Title
A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why Stopped
The DMC recommended the trial be discontinued due to futility following a planned second interim analysis.
Study Start Date
July 25, 2022 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
March 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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)
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) the treating physician agrees to participate in the program.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Reldesemtiv 300 mg twice daily
Arm Type
Experimental
Arm Description
Patients in this arm take 1 reldesemtiv 300 mg oral tablet twice a day for a 600 mg total daily dose (TDD)
Intervention Type
Drug
Intervention Name(s)
Reldesemtiv
Intervention Description
Oral tablet
Primary Outcome Measure Information:
Title
Long-term safety and tolerability of reldesemtiv in patients with ALS
Description
The incidence of adverse events (AEs) in the patient population
Time Frame
Baseline to Week 48
Secondary Outcome Measure Information:
Title
Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031
Description
• 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
Time Frame
Baseline to Week 48
Title
Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031
Description
Time to the first hospitalization from Day 1 in CY 5031 through Week 48 of CY 5032
Time Frame
Baseline to Week 48
Title
Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031
Description
• 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.
Time Frame
Baseline to Week 48
Title
Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031
Description
• 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
Time Frame
Baseline to Week 48
Title
Long-term effect of reldesemtiv on ALSFRS-R functional outcomes and hospitalization by comparing early-start to delayed-start groups from CY 5031
Description
• 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
Time Frame
Baseline to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cytokinetics MD
Organizational Affiliation
Scientific Leadership at Cytokinetics
Official's Role
Study Chair
Facility Information:
Facility Name
St. Joseph's Hospital & Medical Center - Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
University of California Irvine - ALS & Neuromuscular Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
California Pacific Medical Center - Forbes Norris MDA/ALS Research Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
University of Colorado Hospital Anschutz Outpatient Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
George Washington Medical Faculty Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Indiana University IU Health Neuroscience Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
43202
Country
United States
Facility Name
The University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Johns Hopkins Outpatient Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Michigan Medicine
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Neurology Associates
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68506
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
SUNY Upstate Medical University Institute for Human Performance
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Atrium Health Neuroscience Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Texas Neurology, P.A.
City
Dallas
State/Province
Texas
ZIP/Postal Code
75206
Country
United States
Facility Name
Virginia Commonwealth University
City
Henrico
State/Province
Virginia
ZIP/Postal Code
23233
Country
United States
Facility Name
Froedtert Hospital - Department of Neurology
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Concord Repatriation General Hospital
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital, Neurology Department
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
The Perron Institute
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
Uz Leuven Gasthuisberg Department of Neurology
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
University of Calgary - Heritage Medical Research Clinic
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G1Z1
Country
Canada
Facility Name
Stan Cassidy Centre for Rehabilitation
City
Fredericton
State/Province
New Brunswick
ZIP/Postal Code
E3B 0C7
Country
Canada
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N4K1
Country
Canada
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y4E9
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Montreal Neurological Institute and Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
Facility Name
University of Saskatchewan
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7K0M7
Country
Canada
Facility Name
CHU de Quebec-Universite Laval
City
Quebec
ZIP/Postal Code
G1J1Z4
Country
Canada
Facility Name
RSCI Education and Research Center Beaumount Hospital
City
Dublin
ZIP/Postal Code
9
Country
Ireland
Facility Name
IRCCS Istituto Auxologico Italiano Ospedale San Luca U.O. Neurologia e Stroke Unit
City
Milan
ZIP/Postal Code
20149
Country
Italy
Facility Name
AOU Citta della Salute e della Scienza di Torino Universita degli Studi di Torino P.O. Mollinette - Dipartimento de Neuroscienze "Rita Levi Montalcini"
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
UMC Utrecht Department of Neurology, ALS Center
City
Utrecht
ZIP/Postal Code
3584
Country
Netherlands
Facility Name
Hospital San Rafael
City
Madrid
ZIP/Postal Code
28016
Country
Spain
Facility Name
Hospital Universitario y Politecnico La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Studieenheten, Akademiskt Specialistcentrum
City
Stockholm
ZIP/Postal Code
113 61
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

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

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