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A Study for Patients Who Completed VITALITY-ALS (CY 4031)

Phase 3
Completed
Conditions
Amyotrophic Lateral Sclerosis (ALS)
Interventions
Registration Number
NCT02936635
Lead Sponsor
Cytokinetics
Brief Summary

The purpose of this study is to assess the long-term safety and tolerability of tirasemtiv in patients with ALS who had completed the double-blind placebo-controlled study of tirasemtiv in ALS (CY 4031).

Detailed Description

Enrolled participants will begin dosing of tirasemtiv 125 mg twice daily (250 mg/day) for a period of 4 weeks and will titrate to their tolerated dose, the maximum dose being 250 mg twice daily (500 mg/day). This study will also compare the clinical course of patients who completed treatment with tirasemtiv in CY 4031 with those who completed treatment with placebo in CY 4031 during continued treatment of both groups with tirasemtiv during CY 4033, compare the clinical course of patients who completed treatment with tirasemtiv in CY 4031 during that study with their clinical course during continued treatment with tirasemtiv during CY 4033, and compare the clinical course of patients who completed treatment with placebo in CY 4031 during that study with their clinical course during treatment with tirasemtiv during CY 4033.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
280
Inclusion Criteria
  • Able to comprehend and willing to sign an Informed Consent Form (ICF). If verbal consent is given, a Legal Designee of the patient must sign the ICF form

  • Completed participation on study drug and the Follow-Up Visit in the CY 4031 study

  • Male patients, who have not had a vasectomy AND confirmed zero sperm count, must agree for the duration of their participation in the study to either:

    • Use a condom during sexual intercourse with female partners who are of childbearing potential AND to have female partners use a highly effective means of contraception OR
    • Abstain from sexual intercourse during participation in the study
  • Female patients who are not post-menopausal (≥ 1 year) or sterilized, must:

    • Not be breastfeeding
    • Have a negative pregnancy test
    • Have no intention to become pregnant during participation in the study AND
    • Practice sexual abstinence, defined as refraining from intercourse during the duration of the study OR if male partners are not vasectomized with a confirmed zero sperm count, require use of a condom AND use of a highly effective contraceptive measure
Exclusion Criteria
  • Has a diaphragm pacing system (DPS) at study entry or anticipate DPS placement during the course of the study
  • Has taken an investigational study drug (other than tirasemtiv) prior to dosing, within 30 days or five half-lives of the prior agent, whichever is greater
  • Use of tizanidine and theophylline-containing medications during study participation
  • Participation or planning to participate in any form of stem cell therapy for the treatment of ALS or another investigational drug

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Early Start TreatmenttirasemtivThe Early Start Treatment group consisted of patients who received tirasemtiv in both CY 4031 and CY 4033.
Delayed Start TreatmenttirasemtivThe Delayed Start Treatment group consisted of patients who received placebo in CY 4031 and tirasemtiv in CY 4033.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse EventsFrom the first dose of tirasemtiv through 28 days after the last dose

The number of participants with adverse events was used as the measure for the long-term safety and tolerability of tirasemtiv.

Secondary Outcome Measures
NameTimeMethod
Change From CY 4031 Baseline in Percent Predicted Slow Vital Capacity to Week 24 in CY 4033baseline and 24 weeks

Slow vital capacity (SVC) 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 (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics \[eg, height, age, sex\]).

Change From CY 4031 Baseline in Percent Predicted Slow Vital Capacity to Week 48 in CY 4033baseline and 48 weeks

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 (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics \[eg, height, age, sex\]).

Change From CY 4031 Baseline in ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score at Week 24baseline and 24 weeks

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, with higher scores reflecting more normal function and lower scores reflecting more impaired function. Comparing postbaseline to baseline assessments, a negative value indicates a worsening in function.

Change From CY 4031 Baseline in ALSFRS-R Total Score at Week 48baseline and 48 weeks

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, with higher scores reflecting more normal function and lower scores reflecting more impaired function. Comparing postbaseline to baseline assessments, a negative value indicates a worsening in function.

Trial Locations

Locations (67)

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Stanford Hospital and Clinics

🇺🇸

Stanford, California, United States

The Emory Clinic

🇺🇸

Atlanta, Georgia, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

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

🇺🇸

Worcester, Massachusetts, United States

Barnes-Jewish Hospital

🇺🇸

Saint Louis, Missouri, United States

St. Louis University, Department of Neurology & Psychiatry

🇺🇸

Saint Louis, Missouri, United States

SUNY Upstate Medical University

🇺🇸

Syracuse, New York, United States

Neurological Institute

🇺🇸

New York, New York, United States

Hospital for Special Surgery

🇺🇸

New York, New York, United States

Neurosciences Institute, Neurology - Charlotte

🇺🇸

Charlotte, North Carolina, United States

The Ohio State University Wexner Medical Center

🇺🇸

Columbus, Ohio, United States

Penn State Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Texas Neurology, PA

🇺🇸

Dallas, Texas, United States

Temple University School of Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

West Virginia University Hospitals

🇺🇸

Morgantown, West Virginia, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

UZ Leuven

🇧🇪

Leuven, Vlaams Brabant, Belgium

University of Calgary

🇨🇦

Calgary, Alberta, Canada

QE II Health Sciences, Nova Scotia Health Authority

🇨🇦

Halifax, Nova Scotia, Canada

London Health Sciences Centre

🇨🇦

London, Ontario, Canada

Stan Cassidy Centre for Rehabilitation

🇨🇦

Fredericton, New Brunswick, Canada

McMaster University Medical Centre

🇨🇦

Hamilton, Ontario, Canada

Sunnybrook Health Sciences Center

🇨🇦

Toronto, Ontario, Canada

Hopital Dupuytren, service de neurologie

🇫🇷

Limoges Cedex, France

University of Ulm, Department of Neurology

🇩🇪

Ulm, Baden-Wuerttemberg, Germany

Hannover Medical School, Department of Neurology

🇩🇪

Hannover, Lower Saxony, Germany

Hopital Gui de chauliac

🇫🇷

Montpellier Cedex 5, France

Hopital Bretonneau

🇫🇷

Tours cedex 9, France

CHU de Nice - Hopital Pasteur 2

🇫🇷

Nice Cedex 1, France

Charite Campus Virchow-Klinikum, Department of Neurology

🇩🇪

Berlin, Germany

Hospital San Rafael

🇪🇸

Madrid, Spain

King's College Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"

🇮🇹

Torino, Piemonte, Italy

University of California, Irvine

🇺🇸

Orange, California, United States

CHU de Quebec - Univerite' Laval

🇨🇦

Quebec City, Quebec, Canada

Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Hospital for Special Care

🇺🇸

New Britain, Connecticut, United States

George Washington University Medical Center

🇺🇸

Washington, District of Columbia, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

Clinical Research Centre Beaumont Hospital

🇮🇪

Dublin, Ireland

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda, Ospedale Niguarda

🇮🇹

Milan, Lombardy, Italy

Hopital Notre-Dame/CHUM

🇨🇦

Montreal, Quebec, Canada

Montreal Neurological Institute and Hospital

🇨🇦

Montreal, Quebec, Canada

IRCCS Istituto Auxologico Italiano - U.O. Neurologia

🇮🇹

Milan, Lombardy, Italy

Hospital Santa Maria - Centro Hospitalar Lisboa Norte

🇵🇹

Lisboa, Portugal

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Froedtert Memorial Lutheran Hospital

🇺🇸

Milwaukee, Wisconsin, United States

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

🇺🇸

Phoenix, Arizona, United States

University of Miami, Miller School of Medicine

🇺🇸

Miami, Florida, United States

Duke Neurological Disorders Clinic

🇺🇸

Durham, North Carolina, United States

Forbes Norris MDA/ALS Research Center

🇺🇸

San Francisco, California, United States

University of Colorado Hospital Anschutz Outpatient Pavilion

🇺🇸

Aurora, Colorado, United States

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

🇺🇸

Tampa, Florida, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Vanderbilt University Medical Center - Clinical Research Center

🇺🇸

Nashville, Tennessee, United States

Providence Brain and Spine Inst. ALS Center

🇺🇸

Portland, Oregon, United States

University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

UTHSCSA - First Outpatient Research Unit

🇺🇸

San Antonio, Texas, United States

UC Davis Medical Center

🇺🇸

Sacramento, California, United States

University of Michigan Health System

🇺🇸

Ann Arbor, Michigan, United States

Department of Neurology, Wake Forest School of Medicine

🇺🇸

Winston-Salem, North Carolina, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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