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

A Phase 3, Open-Label Extension Study of Tirasemtiv for Patients With Amyotrophic Lateral Sclerosis (ALS) Who Completed VITALITY-ALS (CY 4031)

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).

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: tirasemtiv

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.

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 1Z1
      • University of Alberta
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 0C7
      • Stan Cassidy Centre for Rehabilitation
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QE II Health Sciences, Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Center
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre-Dame/CHUM
    • Quebec City, Quebec, Canada, G1J 1Z4
      • CHU de Quebec - Univerite' Laval
• France
  • Limoges Cedex, France, 87042
    • Hopital Dupuytren, service de neurologie
  • Montpellier Cedex 5, France, 34295
    • Hopital Gui de Chauliac
  • Nice Cedex 1, France, 06001
    • CHU de Nice - Hôpital Pasteur 2
  • Tours cedex 9, France, 37044
    • Hôpital Bretonneau
• Germany
  • Berlin, Germany, 13353
    • Charite Campus Virchow-Klinikum, Department of Neurology
  • Baden-Wuerttemberg
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • University of Ulm, Department of Neurology
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Hannover Medical School, Department of Neurology
• Ireland
  • Dublin, Ireland, Dublin 9
    • Clinical Research Centre Beaumont Hospital
• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20149
      • IRCCS Istituto Auxologico Italiano - U.O. Neurologia
    • Milan, Lombardy, Italy, 20162
      • Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda, Ospedale Niguarda
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• Portugal
  • Lisboa, Portugal, 1649-035
    • Hospital Santa Maria - Centro Hospitalar Lisboa Norte
• Spain
  • Madrid, Spain, 28016
    • Hospital San Rafael
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • University of California, Irvine
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • 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 Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Miami, Florida, United States, 33136
      • University of Miami, Miller School of Medicine
    • Tampa, Florida, United States, 33512
      • Carol & Frank Morsani Center for Advanced Health Care - University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • 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
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center/University of Massachusetts Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University, Department of Neurology & Psychiatry
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • New York, New York, United States, 10032
      • Neurological Institute
    • 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
      • Department of Neurology, Wake Forest School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Brain and Spine Inst. 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, PA
    • San Antonio, Texas, United States, 78229
      • UTHSCSA - First Outpatient Research Unit
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospitals
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delayed Start Treatment; The Delayed Start Treatment group consisted of patients who received placebo in CY 4031 and tirasemtiv in CY 4033.	Drug: tirasemtiv; Oral; Other Names: CK-2017357
Experimental: Early Start Treatment; The Early Start Treatment group consisted of patients who received tirasemtiv in both CY 4031 and CY 4033.	Drug: tirasemtiv; Oral; Other Names: CK-2017357

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	The number of participants with adverse events was used as the measure for the long-term safety and tolerability of tirasemtiv.	From the first dose of tirasemtiv through 28 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From CY 4031 Baseline in Percent Predicted Slow Vital Capacity to Week 24 in CY 4033	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]).	baseline and 24 weeks
Change From CY 4031 Baseline in Percent Predicted Slow Vital Capacity to Week 48 in CY 4033	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]).	baseline and 48 weeks
Change From CY 4031 Baseline in ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score at Week 24	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.	baseline and 24 weeks
Change From CY 4031 Baseline in ALSFRS-R Total Score at Week 48	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.	baseline and 48 weeks

Collaborators and Investigators

• Sponsor: Cytokinetics
• Investigators: Study Director: MD, Cytokinetics, Cytokinetics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2016
• Primary Completion (Actual): October 26, 2018
• Study Completion (Actual): October 26, 2018

Study Registration Dates

• First Submitted: October 12, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (Estimate): October 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; tirasemtiv
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: CY 4033; 2016-002629-13 (EudraCT Number)