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

Amyotrophic Lateral Sclerosis (ALS) Clinical Trial

— VIGOR-ALS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02936635
• Other study ID #: CY 4033
• Secondary ID: 2016-002629-13
• Status: Completed
• Phase: Phase 3
• Start date: October 17, 2016
• Est. completion date: October 26, 2018

Study information

• Verified date: May 2021
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: October 26, 2018
• Est. primary completion date: October 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• tirasemtiv
Oral

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Stan Cassidy Centre for Rehabilitation	Fredericton	New Brunswick
Canada	QE II Health Sciences, Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Hopital Notre-Dame/CHUM	Montreal	Quebec
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	CHU de Quebec - Univerite' Laval	Quebec City	Quebec
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
France	Hopital Dupuytren, service de neurologie	Limoges Cedex
France	Hopital Gui de chauliac	Montpellier Cedex 5
France	CHU de Nice - Hopital Pasteur 2	Nice Cedex 1
France	Hopital Bretonneau	Tours cedex 9
Germany	Charite Campus Virchow-Klinikum, Department of Neurology	Berlin
Germany	Hannover Medical School, Department of Neurology	Hannover	Lower Saxony
Germany	University of Ulm, Department of Neurology	Ulm	Baden-Wuerttemberg
Ireland	Clinical Research Centre Beaumont Hospital	Dublin
Italy	Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda, Ospedale Niguarda	Milan	Lombardy
Italy	IRCCS Istituto Auxologico Italiano - U.O. Neurologia	Milan	Lombardy
Italy	Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"	Torino	Piemonte
Netherlands	University Medical Center Utrecht	Utrecht
Portugal	Hospital Santa Maria - Centro Hospitalar Lisboa Norte	Lisboa
Spain	Hospital San Rafael	Madrid
United Kingdom	King's College Hospital NHS Foundation Trust	London
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	The Emory Clinic	Atlanta	Georgia
United States	University of Colorado Hospital Anschutz Outpatient Pavilion	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Neurosciences Institute, Neurology - Charlotte	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Texas Neurology, PA	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke Neurological Disorders Clinic	Durham	North Carolina
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University	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	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Miami, Miller School of Medicine	Miami	Florida
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	West Virginia University Hospitals	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	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 Neurology Clinics	Phoenix	Arizona
United States	Providence Brain and Spine Inst. ALS Center	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	St. Louis University, Department of Neurology & Psychiatry	Saint Louis	Missouri
United States	UTHSCSA - First Outpatient Research Unit	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 Health Care - University of South Florida	Tampa	Florida
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Department of Neurology, 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 (1)

Lead Sponsor	Collaborator
Cytokinetics

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Ireland,  Italy,  Netherlands,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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