A Study to Evaluate Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)

NCT03160898 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CY 5022
• Study Type: interventional
• Target: 458
• Locations: 6 countries
• Sites: 64

Brief Summary

The purpose of this study was to assess the effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on respiratory function and other measures of skeletal muscle function in patients with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; ALS; CK-2127107; Reldesemtiv

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)

  Slow vital capacity was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). Values obtained were converted to percent predicted values using the Global Lung Initiative equation (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics \[eg, height, age, sex\]).

  Baseline to Week 12

Secondary Outcomes (2)

• Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score

  Baseline to Week 12

• Slope of Muscle Strength Mega-score From Baseline to Week 12

  Baseline to Week 12

Study Arms (4)

Reldesemtiv 150 mg twice daily

EXPERIMENTAL

Patients in this arm took 1 reldesemtiv 150 mg oral tablet and 2 matching placebo tablets every 12 hours for 12 weeks.

Drug: Reldesemtiv

Reldesemtiv 300 mg twice daily

EXPERIMENTAL

Patients in this arm took 2 reldesemtiv 150 mg oral tablets and 1 matching placebo tablet every 12 hours for 12 weeks.

Drug: Reldesemtiv

Reldesemtiv 450 mg twice daily

EXPERIMENTAL

Patients in this arm took 3 reldesemtiv 150 mg oral tablets every 12 hours for 12 weeks.

Drug: Reldesemtiv

Placebo

PLACEBO COMPARATOR

Patients in this arm took 3 placebo oral tablets every 12 hours for 12 weeks.

Drug: Placebo

Interventions

Reldesemtiv DRUG

Oral tablet

Also known as: CK-2127107

Reldesemtiv 150 mg twice daily; Reldesemtiv 300 mg twice daily; Reldesemtiv 450 mg twice daily

Placebo DRUG

Oral tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of familial or sporadic ALS ≤ 24 months prior to screening
• Upright Slow Vital Capacity (SVC) ≥ 60% of predicted for age, height and sex at screening
• Able to swallow tablets
• A caregiver (if one is needed)
• Able to perform reproducible pulmonary function tests
• Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
• Male patients who have not had a vasectomy and confirmed zero sperm count must agree after receiving the first dose of study drug until 10 weeks after the last dose to either use acceptable methods of contraception or abstain from sex
• Female patients must be post-menopausal or sterilized or must not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the study and use acceptable methods of contraception or abstain from heterosexual intercourse from Screening until 10 weeks after last dose of study drug
• Patients must be either on riluzole for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and not planning to start riluzole during the course of the study.
• Patients on edaravone must have completed at least 2 cycles of dosing with edaravone at the time of screening or have not taken edaravone for at least 30 days prior to screening and not planning to start edaravone during the course of the study.

You may not qualify if:

• At the time of screening, any use of non-invasive ventilation (NIV), e.g. continuous positive airway pressure \[CPAP\], noninvasive bi-level positive airway pressure \[NPPV\] or noninvasive volume ventilation \[NVV\] for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
• Neurological impairment due to a condition other than ALS
• Presence at screening of any medically significant cardiac, pulmonary, GI, 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
• Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
• Known to have received CK-2127107 or tirasemtiv in any previous clinical trial
• Has received or is considering receiving during the course of the study any form of stem cell therapy for the treatment of ALS
• Has received or is considering receiving during the course of the study any form of gene therapy for the treatment of ALS
• Has received or is considering obtaining during the course of the study a diaphragmatic pacing system
• History of substance abuse within the past 2 years
• Use of certain medications

Sponsors & Collaborators

• Cytokinetics: lead
• Astellas Pharma Inc: collaborator

Study Sites (64)

St. Joseph's Hospital and Medical Center - Barrow Neurological Clinics

Phoenix, Arizona, 85013, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Forbes Norris MDA/ALS Research Center

San Francisco, California, 94115, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Colorado Hospital Anschutz Outpatient Pavilion

Aurora, Colorado, 80045, United States

Location

Hospital for Special Care

New Britain, Connecticut, 06053, United States

Location

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Carol & Frank Morsani Center for Advanced Healthcare - University of South Florida

Tampa, Florida, 33612, United States

Location

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Duchossois Center for Advanced Medicine

Chicago, Illinois, 60637, United States

Location

IU Health Neuroscience Center of Excellence

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University - Outpatient Center

Baltimore, Maryland, 21287, United States

Location

University of Massachusetts Memorial Medical Center/University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Louis University, Department of Neurology

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Neurology Associates, P.C.

Lincoln, Nebraska, 68506, United States

Location

Hospital For Special Surgery

New York, New York, 10021, United States

Location

Neurological Institute, Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Neurosciences Institute, Neurology - Charlotte

Charlotte, North Carolina, 28207, United States

Location

Duke Neurological Disorders Clinic

Durham, North Carolina, 27705, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Providence Brain and Spine Institute ALS Center

Portland, Oregon, 97213, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Vanderbilt University Medical Center - Clinical Research Center

Nashville, Tennessee, 37232, United States

Location

Texas Neurology

Dallas, Texas, 75214, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

UTHSCSA Medical Arts and Research Center

San Antonio, Texas, 78229, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05405, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

VCU Health - Ambulatory Care Center (ACC)

Richmond, Virginia, 23298, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

West Virginia University, Dept. of Neurology

Morgantown, West Virginia, 26506-9180, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Brain and Mind Centre, The University of Sydney

Camperdown, New South Wales, 2050, Australia

Location

Department of Neurology, Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

The Perron Institute for Neurological and Translation Science

Nedlands, Western Australia, 6009, Australia

Location

University of Calgary, Heritage Medical Research Center

Calgary, Alberta, T2N 4Z6, Canada

Location

Edmonton Kaye Clinic

Edmonton, Alberta, T6GT 1Z1, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Health Sciences Centre University Hospital

London, Ontario, N6A 5A5, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Centre de recherche du Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 0A9, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Saskatoon City Hospital

Saskatoon, Saskatchewan, S7H 0G9, Canada

Location

CHU de Quebec-Universite Laval, Hopital de l'Enfant Jesus

Québec, G1J 1Z4, Canada

Location

Beaumont Hospital

Dublin, Dublin 9, Ireland

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital San Rafael Servicio de Neurologia

Madrid, 28016, Spain

Location

Related Publications (5)

• Shefner JM, Al-Chalabi A, Andrews JA, Chio A, De Carvalho M, Cockroft BM, Corcia P, Couratier P, Cudkowicz ME, Genge A, Hardiman O, Heiman-Patterson T, Henderson RD, Ingre C, Jackson CE, Johnston W, Lechtzin N, Ludolph A, Maragakis NJ, Miller TM, Mora Pardina JS, Petri S, Simmons Z, Van Den Berg LH, Zinman L, Kupfer S, Malik FI, Meng L, Simkins TJ, Wei J, Wolff AA, Rudnicki SA. COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success. Amyotroph Lateral Scler Frontotemporal Degener. 2023 Aug;24(5-6):523-534. doi: 10.1080/21678421.2023.2216223. Epub 2023 May 30.

  PMID: 37254449 DERIVED

• Gebrehiwet P, Meng L, Rudnicki SA, Sarocco P, Wei J, Wolff AA, Chio A, Andrews JA, Genge A, Jackson CE, Lechtzin N, Miller TM, Shefner JM. MiToS and King's staging as clinical outcome measures in ALS: a retrospective analysis of the FORTITUDE-ALS trial. Amyotroph Lateral Scler Frontotemporal Degener. 2023 May;24(3-4):304-310. doi: 10.1080/21678421.2022.2154678. Epub 2022 Dec 12.

  PMID: 36503310 DERIVED

• Rudnicki SA, Andrews JA, Genge A, Jackson C, Lechtzin N, Miller TM, Cockroft BM, Malik FI, Meng L, Wei J, Wolff AA, Shefner JM; FORTITUDE-ALS STUDY GROUP. Prescription and acceptance of durable medical equipment in FORTITUDE-ALS, a study of reldesemtiv in ALS: post hoc analyses of a randomized, double-blind, placebo-controlled clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2022 May;23(3-4):263-270. doi: 10.1080/21678421.2021.1946083. Epub 2021 Jul 5.

  PMID: 34218726 DERIVED

• Shefner JM, Andrews JA, Genge A, Jackson C, Lechtzin N, Miller TM, Cockroft BM, Meng L, Wei J, Wolff AA, Malik FI, Bodkin C, Brooks BR, Caress J, Dionne A, Fee D, Goutman SA, Goyal NA, Hardiman O, Hayat G, Heiman-Patterson T, Heitzman D, Henderson RD, Johnston W, Karam C, Kiernan MC, Kolb SJ, Korngut L, Ladha S, Matte G, Mora JS, Needham M, Oskarsson B, Pattee GL, Pioro EP, Pulley M, Quan D, Rezania K, Schellenberg KL, Schultz D, Shoesmith C, Simmons Z, Statland J, Sultan S, Swenson A, Berg LHVD, Vu T, Vucic S, Weiss M, Whyte-Rayson A, Wymer J, Zinman L, Rudnicki SA. A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2021 May;22(3-4):287-299. doi: 10.1080/21678421.2020.1822410. Epub 2020 Sep 24.

  PMID: 32969758 DERIVED

• Shefner JM, Cudkowicz ME, Hardiman O, Cockcroft BM, Lee JH, Malik FI, Meng L, Rudnicki SA, Wolff AA, Andrews JA; VITALITY-ALS Study Group. A phase III trial of tirasemtiv as a potential treatment for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2019;0(0):1-11. doi: 10.1080/21678421.2019.1612922.

  PMID: 31081694 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

reldesemtiv

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: MD Cytokinetics
• Organization: Cytokinetics, Inc.

medicalaffairs@cytokinetics.com

650-624-2929

Study Officials

• MD Cytokinetics

  Cytokinetics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2017
• First Posted: May 19, 2017
• Study Start: July 24, 2017
• Primary Completion: March 7, 2019
• Study Completion: March 7, 2019
• Last Updated: September 11, 2020
• Results First Posted: September 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); CA (9); US (47); AU (5); ES (1); IE (1)