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

August 21, 2020 updated by: Cytokinetics

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

458

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reldesemtiv 150 mg twice daily
Patients in this arm took 1 reldesemtiv 150 mg oral tablet and 2 matching placebo tablets every 12 hours for 12 weeks.
Drug: Reldesemtiv
Oral tablet
Other Names:
  • CK-2127107
Experimental: Reldesemtiv 300 mg twice daily
Patients in this arm took 2 reldesemtiv 150 mg oral tablets and 1 matching placebo tablet every 12 hours for 12 weeks.
Drug: Reldesemtiv
Oral tablet
Other Names:
  • CK-2127107
Experimental: Reldesemtiv 450 mg twice daily
Patients in this arm took 3 reldesemtiv 150 mg oral tablets every 12 hours for 12 weeks.
Drug: Reldesemtiv
Oral tablet
Other Names:
  • CK-2127107
Placebo Comparator: Placebo
Patients in this arm took 3 placebo oral tablets every 12 hours for 12 weeks.
Drug: Placebo
Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)
Time Frame: Baseline to Week 12
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score
Time Frame: Baseline to Week 12
The ALSFRS-R is used to measure the progression and severity of disability in patients with ALS. The ALSFRS-R consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in the following 4 domains: gross motor tasks, fine motor tasks, bulbar functions, and respiratory function. Each question is scored from 0 (indicating incapable or dependent) to 4 (normal). The total score ranges from 0 to 48. Higher scores reflect more normal function and lower scores reflect more impaired function.
Baseline to Week 12
Slope of Muscle Strength Mega-score From Baseline to Week 12
Time Frame: Baseline to Week 12
A hand-held dynamometer, with a scale of 0 to 300 pounds, was used to measure muscle strength and handgrip strength (bilateral). The muscle groups tested were: elbow flexion, wrist extension, first dorsal interosseous, hip flexion, knee extension, and ankle dorsiflexion; all muscle groups were evaluated bilaterally. For each postbaseline assessment of muscle strength, the percent change from baseline was calculated for each muscle group and handgrip strength, using the following equation: ([postbaseline value - baseline value] / baseline value) × 100. The muscle-strength mega-score was calculated as the average of the changes (ie, percent change from baseline) observed for each of the muscle groups as well as handgrip strength. For this endpoint, negative values indicate a decline in muscle strength.
Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cytokinetics

Collaborators

Astellas Pharma Inc

Investigators

  • Study Director: MD Cytokinetics, Cytokinetics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 24, 2017

Primary Completion (Actual)

March 7, 2019

Study Completion (Actual)

March 7, 2019

Study Registration Dates

First Submitted

May 12, 2017

First Submitted That Met QC Criteria

May 17, 2017

First Posted (Actual)

May 19, 2017

Study Record Updates

Last Update Posted (Actual)

September 11, 2020

Last Update Submitted That Met QC Criteria

August 21, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CY 5022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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