Study of Safety, Tolerability & Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis (ALS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cytokinetics
ClinicalTrials.gov Identifier:
NCT01709149
First received: October 16, 2012
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The purpose of this research study is to evaluate the safety and effectiveness of CK-2017357 when taken with or without riluzole (also called Rilutek®) in patients with Amyotrophic Lateral Sclerosis (ALS).


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: CK-2017357
Other: Placebo tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIb, Multi-National, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Efficacy of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS) (BENEFIT-ALS)

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • The change from baseline to the average of the ALS Functional Rating Scale-Revised (ALSFRS-R) total score obtained at Visits 6 and 7 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Maximum Voluntary Ventilation (MVV) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in Sniff Nasal Inspiratory Pressure (SNIP) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in Slow Vital Capacity (SVC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in handgrip strength and fatigability [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    As measured by maximum handgrip strength and sub-maximum handgrip strength

  • Change in muscle strength by hand-held dynamometry (HHD) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    As determined by the megascore of:

    Elbow flexion (bilateral), wrist extension (bilateral), knee extension (bilateral), and ankle dorsiflexion (bilateral)



Estimated Enrollment: 680
Study Start Date: October 2012
Study Completion Date: March 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CK-2017357
125 mg tablets
Drug: CK-2017357
Other Name: tirasemtiv
Placebo Comparator: Placebo
Placebo tablets
Other: Placebo tablets

Detailed Description:

The length of the study, including screening, dosing, and follow-up, is approximately 20 weeks. After a one-week open-label phase during which all patients will receive CK-2017357 125 milligrams (mg) twice daily, patients will be randomized one to one (fifty-fifty) to receive double-blind CK-2017357 or matching placebo. The CK-2017357/placebo dose will be increased no faster than weekly to each patient's highest tolerated daily dose, with a maximum of 250 mg twice daily. The dose may be decreased based on tolerability. Patients will continue treatment at the highest tolerated dose to complete a total of 12 weeks of double-blind treatment. Patients may be on riluzole or not on riluzole at study entry. Patients not on riluzole must stay off riluzole. Patients on riluzole who are getting double-blind CK-2017357 will be given riluzole at half the labeled dosage (50 mg once a day instead of 50 mg twice a day). Blood tests for safety will be performed. Information about any side effects that may occur will also be collected.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
  2. Male or female 18 years of age or older
  3. 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)
  4. Upright Slow Vital Capacity (SVC) >60 % of predicted for age, height and sex
  5. At least 4 of the 12 ALSFRS-R questions must be scored 2 or 3
  6. Diminished but measurable maximum voluntary grip strength in at least one hand; i.e., between 10 and 40 pounds (females) and 10 and 60 pounds (males)
  7. Able to swallow tablets without crushing
  8. A caregiver (if one is needed) who can and will observe and report the patient's status
  9. Pre-study clinical laboratory findings within normal range or, if outside of the normal range, deemed not clinically significant by the Investigator
  10. 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 reproductive potential 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
  11. 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 contraceptive drugs or devices as detailed in item 10 for the duration of the study and for 10 weeks after the end of the study
  12. 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 during the conduct of this study.

Exclusion Criteria:

  1. Any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
  2. Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study
  3. Body Mass Index (BMI) of 19.0 kg/m2 or lower
  4. Unwilling to discontinue theophylline-containing medications during study participation
  5. Serum chloride < 100 mmol/L
  6. Neurological impairment due to a condition other than ALS, including history of transient ischemic attack (TIA) within the past year
  7. Presence at screening of any medically significant cardiac, pulmonary, gastrointestinal (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
  8. Has taken any investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
  9. Previously received CK-2017357 in any previous clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709149

  Show 75 Study Locations
Sponsors and Collaborators
Cytokinetics
Investigators
Study Director: Jinsy Andrews, MD Cytokinetics, Inc.
Study Chair: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
Principal Investigator: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
  More Information

No publications provided

Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT01709149     History of Changes
Other Study ID Numbers: CY 4026
Study First Received: October 16, 2012
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014