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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Drug: tirasemtiv


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, ALS, tirasemtiv