Clinical trial NCT03160898: A Study to Evaluate Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
ALS
CK-2127107
Reldesemtiv
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
First posted: 2017-05-19
Enrollment: 458
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score
timeFrame: Baseline to Week 12
measure: Slope of Muscle Strength Mega-score From Baseline to Week 12
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center - Barrow Neurological Clinics
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: Forbes Norris MDA/ALS Research Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavilion
state: Colorado
city: New Britain
country: United States
facility: Hospital for Special Care
state: Connecticut
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: Carol & Frank Morsani Center for Advanced Healthcare - University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Chicago
country: United States
facility: Duchossois Center for Advanced Medicine
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Neuroscience Center of Excellence
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University - Outpatient Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center/University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University, Department of Neurology
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Neurology Associates, P.C.
state: Nebraska
city: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: New York
country: United States
facility: Neurological Institute, Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Neurosciences Institute, Neurology - Charlotte
state: North Carolina
city: Durham
country: United States
facility: Duke Neurological Disorders Clinic
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Brain and Spine Institute ALS Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Clinical Research Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: UTHSCSA Medical Arts and Research Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Richmond
country: United States
facility: VCU Health - Ambulatory Care Center (ACC)
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University, Dept. of Neurology
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Camperdown
country: Australia
facility: Brain and Mind Centre, The University of Sydney
state: New South Wales
city: Westmead
country: Australia
facility: Department of Neurology, Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Nedlands
country: Australia
facility: The Perron Institute for Neurological and Translation Science
state: Western Australia
city: Calgary
country: Canada
facility: University of Calgary, Heritage Medical Research Center
state: Alberta
city: Edmonton
country: Canada
facility: Edmonton Kaye Clinic
state: Alberta
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Montréal
country: Canada
facility: Centre de recherche du Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon City Hospital
state: Saskatchewan
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval, Hopital de l'Enfant Jesus
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Madrid
country: Spain
facility: Hospital San Rafael Servicio de Neurologia
Study officials:
affiliation: Cytokinetics
name: MD Cytokinetics
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.