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

A Phase 2, Multi-Center, Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Sponsors

Lead Sponsor: Cytokinetics

Collaborator: Astellas Pharma Inc

Source Cytokinetics
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.

Detailed Description

This was a double-blind, randomized, placebo-controlled, dose ranging study of reldesemtiv in patients with ALS. Eligible patients were randomized (1:1:1:1) to receive placebo or one of three doses of reldesemtiv (150, 300, or 450 mg twice daily) for 12 weeks. Randomization was stratified by riluzole concomitant use/non-use and edaravone concomitant use/non-use. Concomitant riluzole and edaravone were allowed as long as the riluzole dose had been stable for at least 30 days prior to screening and edaravone had been taken for 2 cycles prior to screening; these drugs could not be initiated during the study. A total of 7 study visits were planned: screening, Day 1 (first dosing day), Weeks 2, 4, 8, and 12, and follow-up (4 weeks after the last dose of study drug). Study drug (placebo or reldesemtiv) was to be taken twice daily, approximately 12 hours (± 2 hours) apart and within 2 hours following a meal.

Overall Status Completed
Start Date 2017-07-24
Completion Date 2019-03-07
Primary Completion Date 2019-03-07
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC) Baseline to Week 12
Secondary Outcome
Measure Time Frame
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
Enrollment 458
Condition
Intervention

Intervention Type: Drug

Intervention Name: Reldesemtiv

Description: Oral tablet

Other Name: CK-2127107

Intervention Type: Drug

Intervention Name: Placebo

Description: Oral tablet

Arm Group Label: Placebo

Eligibility

Criteria:

Inclusion Criteria: - 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. Exclusion Criteria: - 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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
MD Cytokinetics Study Director Cytokinetics
Location
Facility:
St. Joseph's Hospital and Medical Center - Barrow Neurological Clinics | Phoenix, Arizona, 85013, United States
Cedars-Sinai Medical Center | Los Angeles, California, 90048, United States
University of California Irvine | Orange, California, 92868, United States
Forbes Norris MDA/ALS Research Center | San Francisco, California, 94115, United States
Stanford Hospital and Clinics | Stanford, California, 94305, United States
University of Colorado Hospital Anschutz Outpatient Pavilion | Aurora, Colorado, 80045, United States
Hospital for Special Care | New Britain, Connecticut, 06053, United States
George Washington University Medical Faculty Associates | Washington, District of Columbia, 20037, United States
University of Florida | Gainesville, Florida, 32610, United States
Mayo Clinic | Jacksonville, Florida, 32224, United States
Carol & Frank Morsani Center for Advanced Healthcare - University of South Florida | Tampa, Florida, 33612, United States
Emory Clinic | Atlanta, Georgia, 30322, United States
Duchossois Center for Advanced Medicine | Chicago, Illinois, 60637, United States
IU Health Neuroscience Center of Excellence | Indianapolis, Indiana, 46202, United States
University of Iowa Hospitals and Clinics | Iowa City, Iowa, 52242, United States
University of Kansas Medical Center | Kansas City, Kansas, 66160, United States
Johns Hopkins University - Outpatient Center | Baltimore, Maryland, 21287, United States
University of Massachusetts Memorial Medical Center/University of Massachusetts Medical School | Worcester, Massachusetts, 01655, United States
Michigan Medicine | Ann Arbor, Michigan, 48109, United States
Henry Ford Health System | Detroit, Michigan, 48202, United States
Hennepin County Medical Center | Minneapolis, Minnesota, 55415, United States
Mayo Clinic | Rochester, Minnesota, 55905, United States
Saint Louis University, Department of Neurology | Saint Louis, Missouri, 63104, United States
Washington University School of Medicine | Saint Louis, Missouri, 63110, United States
Neurology Associates, P.C. | Lincoln, Nebraska, 68506, United States
Hospital For Special Surgery | New York, New York, 10021, United States
Neurological Institute, Columbia University Medical Center | New York, New York, 10032, United States
SUNY Upstate Medical University | Syracuse, New York, 13210, United States
Neurosciences Institute, Neurology - Charlotte | Charlotte, North Carolina, 28207, United States
Duke Neurological Disorders Clinic | Durham, North Carolina, 27705, United States
Wake Forest School of Medicine | Winston-Salem, North Carolina, 27157, United States
Cleveland Clinic | Cleveland, Ohio, 44195, United States
The Ohio State University Wexner Medical Center | Columbus, Ohio, 43210, United States
Providence Brain and Spine Institute ALS Center | Portland, Oregon, 97213, United States
Oregon Health & Science University | Portland, Oregon, 97239, United States
Penn State Milton S. Hershey Medical Center | Hershey, Pennsylvania, 17033, United States
Temple University School of Medicine | Philadelphia, Pennsylvania, 19140, United States
Vanderbilt University Medical Center - Clinical Research Center | Nashville, Tennessee, 37232, United States
Texas Neurology | Dallas, Texas, 75214, United States
Houston Methodist Hospital | Houston, Texas, 77030, United States
UTHSCSA Medical Arts and Research Center | San Antonio, Texas, 78229, United States
University of Vermont Medical Center | Burlington, Vermont, 05405, United States
University of Virginia Health System | Charlottesville, Virginia, 22908, United States
VCU Health - Ambulatory Care Center (ACC) | Richmond, Virginia, 23298, United States
University of Washington Medical Center | Seattle, Washington, 98195, United States
West Virginia University, Dept. of Neurology | Morgantown, West Virginia, 26506-9180, United States
Froedtert Memorial Lutheran Hospital | Milwaukee, Wisconsin, 53226, United States
Brain and Mind Centre, The University of Sydney | Camperdown, New South Wales, 2050, Australia
Department of Neurology, Westmead Hospital | Westmead, New South Wales, 2145, Australia
Royal Brisbane and Women's Hospital | Herston, Queensland, 4029, Australia
Flinders Medical Centre | Bedford Park, South Australia, 5042, Australia
The Perron Institute for Neurological and Translation Science | Nedlands, Western Australia, 6009, Australia
University of Calgary, Heritage Medical Research Center | Calgary, Alberta, T2N 4Z6, Canada
Edmonton Kaye Clinic | Edmonton, Alberta, T6GT 1Z1, Canada
McMaster University Medical Centre | Hamilton, Ontario, L8N 3Z5, Canada
London Health Sciences Centre University Hospital | London, Ontario, N6A 5A5, Canada
Sunnybrook Health Science Centre | Toronto, Ontario, M4N 3M5, Canada
Montreal Neurological Institute and Hospital | Montreal, Quebec, H3A 2B4, Canada
Centre de recherche du Centre Hospitalier de l'Universite de Montreal | Montréal, Quebec, H2X 0A9, Canada
Saskatoon City Hospital | Saskatoon, Saskatchewan, S7H 0G9, Canada
CHU de Quebec-Universite Laval, Hopital de l'Enfant Jesus | Quebec, G1J 1Z4, Canada
Beaumont Hospital | Dublin, Dublin 9, Ireland
University Medical Center Utrecht | Utrecht, 3584 CX, Netherlands
Hospital San Rafael Servicio de Neurologia | Madrid, 28016, Spain
Location Countries

Australia

Canada

Ireland

Netherlands

Spain

United States

Verification Date

2020-08-01

Responsible Party

Type: Sponsor

Keywords
Condition Browse
Number Of Arms 4
Arm Group

Label: Reldesemtiv 150 mg twice daily

Type: Experimental

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

Label: Reldesemtiv 300 mg twice daily

Type: Experimental

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

Label: Reldesemtiv 450 mg twice daily

Type: Experimental

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

Label: Placebo

Type: Placebo Comparator

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

Acronym FORTITUDE-ALS
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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