We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 6 for:    CK-2127107

A Study to Evaluate Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS) (FORTITUDE-ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03160898
Recruitment Status : Completed
First Posted : May 19, 2017
Results First Posted : September 11, 2020
Last Update Posted : September 11, 2020
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Cytokinetics

Tracking Information
First Submitted Date  ICMJE May 12, 2017
First Posted Date  ICMJE May 19, 2017
Results First Submitted Date  ICMJE August 5, 2020
Results First Posted Date  ICMJE September 11, 2020
Last Update Posted Date September 11, 2020
Actual Study Start Date  ICMJE July 24, 2017
Actual Primary Completion Date March 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2020)
Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC) [ Time Frame: Baseline to Week 12 ]
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 using the Global Lung Initiative equation (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics [eg, height, age, sex]).
Original Primary Outcome Measures  ICMJE
 (submitted: May 17, 2017)
Change from baseline to Week 12 in the percent predicted slow vital capacity (SVC) [ Time Frame: Baseline to Week 12 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2020)
  • Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score [ Time Frame: Baseline to Week 12 ]
    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. Higher scores reflect more normal function and lower scores reflect more impaired function.
  • Slope of Muscle Strength Mega-score From Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    A hand-held dynamometer, with a scale of 0 to 300 pounds, was used to measure muscle strength and handgrip strength (bilateral). The muscle groups tested were: elbow flexion, wrist extension, first dorsal interosseous, hip flexion, knee extension, and ankle dorsiflexion; all muscle groups were evaluated bilaterally. For each postbaseline assessment of muscle strength, the percent change from baseline was calculated for each muscle group and handgrip strength, using the following equation: ([postbaseline value - baseline value] / baseline value) × 100. The muscle-strength mega-score was calculated as the average of the changes (ie, percent change from baseline) observed for each of the muscle groups as well as handgrip strength. For this endpoint, negative values indicate a decline in muscle strength.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2017)
  • Slope of change from baseline in the mega-score of muscle strength measured by hand held dynamometry and handgrip dynamometry from baseline to Week 12 in patients on CK-2127107 compared to placebo [ Time Frame: Baseline to Week 12 ]
  • Change from baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) [ Time Frame: Baseline to Week 12 ]
  • Mean plasma concentrations over time of CK-2127107 at Week 12 [ Time Frame: Day 1 to Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Official Title  ICMJE A Phase 2, Multi-Center, Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Brief Summary The purpose of this study was to assess the effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on respiratory function and other measures of skeletal muscle function in patients with ALS.
Detailed Description

This was a double-blind, randomized, placebo-controlled, dose ranging study of reldesemtiv in patients with ALS. Eligible patients were randomized (1:1:1:1) to receive placebo or one of three doses of reldesemtiv (150, 300, or 450 mg twice daily) for 12 weeks. Randomization was stratified by riluzole concomitant use/non-use and edaravone concomitant use/non-use. Concomitant riluzole and edaravone were allowed as long as the riluzole dose had been stable for at least 30 days prior to screening and edaravone had been taken for 2 cycles prior to screening; these drugs could not be initiated during the study.

A total of 7 study visits were planned: screening, Day 1 (first dosing day), Weeks 2, 4, 8, and 12, and follow-up (4 weeks after the last dose of study drug). Study drug (placebo or reldesemtiv) was to be taken twice daily, approximately 12 hours (± 2 hours) apart and within 2 hours following a meal.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Reldesemtiv
    Oral tablet
    Other Name: CK-2127107
  • Drug: Placebo
    Oral tablet
Study Arms  ICMJE
  • Experimental: Reldesemtiv 150 mg twice daily
    Patients in this arm took 1 reldesemtiv 150 mg oral tablet and 2 matching placebo tablets every 12 hours for 12 weeks.
    Intervention: Drug: Reldesemtiv
  • Experimental: Reldesemtiv 300 mg twice daily
    Patients in this arm took 2 reldesemtiv 150 mg oral tablets and 1 matching placebo tablet every 12 hours for 12 weeks.
    Intervention: Drug: Reldesemtiv
  • Experimental: Reldesemtiv 450 mg twice daily
    Patients in this arm took 3 reldesemtiv 150 mg oral tablets every 12 hours for 12 weeks.
    Intervention: Drug: Reldesemtiv
  • Placebo Comparator: Placebo
    Patients in this arm took 3 placebo oral tablets every 12 hours for 12 weeks.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2019)
458
Original Estimated Enrollment  ICMJE
 (submitted: May 17, 2017)
445
Actual Study Completion Date  ICMJE March 7, 2019
Actual Primary Completion Date March 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of familial or sporadic ALS ≤ 24 months prior to screening
  • Upright Slow Vital Capacity (SVC) ≥ 60% of predicted for age, height and sex at screening
  • Able to swallow tablets
  • A caregiver (if one is needed)
  • Able to perform reproducible pulmonary function tests
  • Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
  • Male patients who have not had a vasectomy and confirmed zero sperm count must agree after receiving the first dose of study drug until 10 weeks after the last dose to either use acceptable methods of contraception or abstain from sex
  • Female patients must be post-menopausal or sterilized or must not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the study and use acceptable methods of contraception or abstain from heterosexual intercourse from Screening until 10 weeks after last dose of study drug
  • Patients must be either on riluzole for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and not planning to start riluzole during the course of the study.
  • Patients on edaravone must have completed at least 2 cycles of dosing with edaravone at the time of screening or have not taken edaravone for at least 30 days prior to screening and not planning to start edaravone during the course of the study.

Exclusion Criteria:

  • At the time of screening, any use of non-invasive ventilation (NIV), e.g. continuous positive airway pressure [CPAP], noninvasive bi-level positive airway pressure [NPPV] or noninvasive volume ventilation [NVV] for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
  • Neurological impairment due to a condition other than ALS
  • 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
  • Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
  • Known to have received CK-2127107 or tirasemtiv in any previous clinical trial
  • Has received or is considering receiving during the course of the study any form of stem cell therapy for the treatment of ALS
  • Has received or is considering receiving during the course of the study any form of gene therapy for the treatment of ALS
  • Has received or is considering obtaining during the course of the study a diaphragmatic pacing system
  • History of substance abuse within the past 2 years
  • Use of certain medications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Ireland,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03160898
Other Study ID Numbers  ICMJE CY 5022
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Cytokinetics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Cytokinetics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Astellas Pharma Inc
Investigators  ICMJE
Study Director: MD Cytokinetics Cytokinetics
PRS Account Cytokinetics
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP