Overview

This trial is active, not recruiting.

Condition amyotrophic lateral sclerosis
Treatments tirasemtiv, placebo tablets
Phase phase 3
Sponsor Cytokinetics
Start date August 2015
End date July 2017
Trial size 743 participants
Trial identifier NCT02496767, 2014-005413-23, CY 4031

Summary

This study is to assess the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Placebo Comparator)
Day 1 through Week 48 - 2 placebo tablets twice daily
placebo tablets
(Experimental)
Day 1 through Week 48 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM
tirasemtiv CK-2017357
placebo tablets
(Experimental)
Day 1 through Week 2 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM; Weeks 3 through 48 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 2 tablets of tirasemtiv (250 mg) in PM
tirasemtiv CK-2017357
placebo tablets
(Experimental)
Day 1 through Week 2 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM; Weeks 3 and 4 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 2 tablets of tirasemtiv (250 mg) in PM; Weeks 5 through 48 - 2 tablets (250 mg) of tirasemtiv in AM and 2 tablets of tirasemtiv (250 mg) in PM
tirasemtiv CK-2017357
placebo tablets

Primary Outcomes

Measure
Change from baseline to Week 24 of the double-blind, placebo-controlled phase in percent predicted slow vital capacity (SVC)
time frame: 24 weeks

Secondary Outcomes

Measure
Time to the first occurrence of a decline from baseline in percent predicted SVC ≥ 20 percentage points or the onset of respiratory insufficiency or death during double-blind, placebo-controlled treatment
time frame: 48 weeks
Time to the first occurrence of a decline in SVC to ≤ 50% predicted or the onset of respiratory insufficiency or death during double-blind, placebo-controlled treatment
time frame: 48 weeks
Time to the first occurrence of the first use of mechanical ventilatory assistance or death during double-blind, placebo-controlled treatment
time frame: 48 weeks
Time to the first occurrence of a decline in the respiratory components of the ALSFRS-R (i.e., items 10, 11, and 12) or death during double-blind, placebo-controlled treatment
time frame: 48 weeks
Slope in muscle strength mega-score change from baseline during the randomized, double-blind, placebo-controlled phase
time frame: 24 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria) ≤ 24 months prior to screening - Upright SVC ≥ 70 % of predicted for age, height and sex - Able to swallow tablets without crushing, and in the opinion of the Investigator, is expected to continue to be able to do so during the trial - A caregiver if one is needed - Clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator - Male patients must agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of childbearing potential (i.e., following menarche until post-menopausal if not anatomically and physiologically incapable of becoming pregnant) and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) or the male patient must agree to abstain from sexual intercourse during and for 10 weeks after the end of the study, unless the male patient has had a vasectomy and confirmed sperm count is zero - Female patients must be post-menopausal (≥ 1 year) or sterilized, or, if of childbearing potential, not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the course of the study, and use effective contraceptive drugs or devices while requiring male partner to use a condom for the duration of the study and for 10 weeks after the end of the study - Patients must be either on a stable dose of riluzole 50 mg twice daily for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and are willing not to begin riluzole use until they complete study drug dosing Exclusion Criteria: - At the time of screening, any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP]) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation - Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study - BMI of 20.0 kg/m2 or lower - Unwilling or unable to discontinue tizanidine and theophylline-containing medications during study participation - Serum chloride outside the normal reference range - Neurological impairment due to a condition other than ALS, including history of transient ischemic attack within the past year - Presence at screening of any medically significant cardiac, pulmonary, GI, musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data, including, but not limited to: 1. Poorly controlled hypertension 2. NYHA Class II or greater congestive heart failure 3. Chronic obstructive pulmonary disease or asthma requiring daily use bronchodilator medications 4. GI disorder that might impair absorption of study drug 5. History of significant liver disease defined by bilirubin > 2 times the upper limit of normal (ULN) or ALT or AST > 3 times the ULN on repeat testing 6. Poorly controlled diabetes mellitus 7. History of vertigo within three months of study entry 8. History of syncope without an explainable or treated cause 9. History of untreated intracranial aneurysm or poorly controlled seizure disorder 10. Amputation of a limb 11. Cognitive impairment, related to ALS or otherwise, sufficient to impair the patient's ability to give informed consent and to understand and/or comply with study procedures 12. Cancer with metastatic potential (other than basal cell carcinoma, carcinoma in situ of the cervix, or squamous cell carcinoma of the skin excised with clean margins) diagnosed and treated within the last two years 13. Any other condition, impairment or social circumstance that, in the opinion of the Investigator, would render the patient not suitable to participate in the study 14. Patient judged to be actively suicidal or a suicide risk by the Investigator - Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is greater, prior to dosing - Prior participation in any form of stem cell therapy for the treatment of ALS - Previously received tirasemtiv in any previous clinical trial

Additional Information

Official title A Phase 3, Multi-National, Double-Blind, Randomized, Placebo-Controlled, Stratified, Parallel Group, Study to Evaluate the Safety, Tolerability and Efficacy of Tirasemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
Description CY 4031 is a multi-national, double-blind, randomized, placebo-controlled, stratified, parallel group study in patients with ALS with the selective fast skeletal muscle troponin activator, tirasemtiv. The study includes three phases; an open-label phase (2 weeks), a double-blind, placebo-controlled phase (48 weeks), and a double-blind, placebo-controlled tirasemtiv withdrawal phase (4 weeks). Patients who can complete two weeks of treatment with open-label tirasemtiv (125 mg twice daily) will be randomized 3:2:2:2 to placebo and three different dose levels of tirasemtiv. Approximately 600 patients will be enrolled onto open-label treatment. Patients who enter the study on riluzole 50 mg twice daily will continue on riluzole but at a reduced dose of 50 mg once daily.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Cytokinetics.