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

Phase 3

Completed

Conditions: Amyotrophic Lateral Sclerosis (ALS)

Interventions: Drug: tirasemtiv

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

Group	Intervention	Description
Early Start Treatment	tirasemtiv	The Early Start Treatment group consisted of patients who received tirasemtiv in both CY 4031 and CY 4033.
Delayed Start Treatment	tirasemtiv	The Delayed Start Treatment group consisted of patients who received placebo in CY 4031 and tirasemtiv in CY 4033.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	From 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

Name	Time	Method
Change From CY 4031 Baseline in Percent Predicted Slow Vital Capacity to Week 24 in CY 4033	baseline 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 4033	baseline 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 24	baseline 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 48	baseline 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): St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics
🇺🇸
Phoenix, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
University of California, Irvine
🇺🇸
Orange, California, United States
UC Davis Medical Center
🇺🇸
Sacramento, California, United States
Forbes Norris MDA/ALS Research Center
🇺🇸
San Francisco, California, United States
Stanford Hospital and Clinics
🇺🇸
Stanford, California, United States
University of Colorado Hospital Anschutz Outpatient Pavilion
🇺🇸
Aurora, Colorado, 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
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St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics
🇺🇸Phoenix, Arizona, United States