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

Amyotrophic Lateral Sclerosis Clinical Trial

— FORTITUDE-ALS  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03160898
• Other study ID #: CY 5022
• Status: Completed
• Phase: Phase 2
• Start date: July 24, 2017
• Est. completion date: March 7, 2019

Study information

• Verified date: August 2020
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 458
• Est. completion date: March 7, 2019
• Est. primary completion date: March 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Reldesemtiv
Oral tablet
• Placebo
Oral tablet

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Brain and Mind Centre, The University of Sydney	Camperdown	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	The Perron Institute for Neurological and Translation Science	Nedlands	Western Australia
Australia	Department of Neurology, Westmead Hospital	Westmead	New South Wales
Canada	University of Calgary, Heritage Medical Research Center	Calgary	Alberta
Canada	Edmonton Kaye Clinic	Edmonton	Alberta
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	London Health Sciences Centre University Hospital	London	Ontario
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Centre de recherche du Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	CHU de Quebec-Universite Laval, Hopital de l'Enfant Jesus	Quebec
Canada	Saskatoon City Hospital	Saskatoon	Saskatchewan
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Ireland	Beaumont Hospital	Dublin
Netherlands	University Medical Center Utrecht	Utrecht
Spain	Hospital San Rafael Servicio de Neurologia	Madrid
United States	Michigan Medicine	Ann Arbor	Michigan
United States	Emory Clinic	Atlanta	Georgia
United States	University of Colorado Hospital Anschutz Outpatient Pavilion	Aurora	Colorado
United States	Johns Hopkins University - Outpatient Center	Baltimore	Maryland
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Neurosciences Institute, Neurology - Charlotte	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Duchossois Center for Advanced Medicine	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Texas Neurology	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke Neurological Disorders Clinic	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	IU Health Neuroscience Center of Excellence	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Neurology Associates, P.C.	Lincoln	Nebraska
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	West Virginia University, Dept. of Neurology	Morgantown	West Virginia
United States	Vanderbilt University Medical Center - Clinical Research Center	Nashville	Tennessee
United States	Hospital for Special Care	New Britain	Connecticut
United States	Hospital For Special Surgery	New York	New York
United States	Neurological Institute, Columbia University Medical Center	New York	New York
United States	University of California Irvine	Orange	California
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center - Barrow Neurological Clinics	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Providence Brain and Spine Institute ALS Center	Portland	Oregon
United States	VCU Health - Ambulatory Care Center (ACC)	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Saint Louis University, Department of Neurology	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UTHSCSA Medical Arts and Research Center	San Antonio	Texas
United States	Forbes Norris MDA/ALS Research Center	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford Hospital and Clinics	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Carol & Frank Morsani Center for Advanced Healthcare - University of South Florida	Tampa	Florida
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center/University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Cytokinetics	Astellas Pharma Inc

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Ireland,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score	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
Secondary	Slope of Muscle Strength Mega-score From 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