AzTrials
AzTrials

Amyotrophic Lateral SclerosisPhase 2NCT01709149

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

A Phase 2 study testing CK-2017357 and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 75 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Amyotrophic Lateral Sclerosis
What is being tested?
CK-2017357 and Riluzole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
711 participants
Where
75 sitesin 8 countries
Study dates
Oct 2012to Mar 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to comprehend and willing to sign an Informed Consent Form (ICF)
  • Male or female 18 years of age or older
  • 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)
  • Upright Slow Vital Capacity (SVC) >50 % of predicted for age, height and sex
  • At least 4 of the 12 ALSFRS-R questions must be scored 2 or 3
  • Diminished but measurable maximum voluntary grip strength in at least one hand; i.e., between 10 and 50 pounds (females) and 10 and 70 pounds (males)
Show all 12Show fewer
  • Able to swallow tablets without crushing
  • A caregiver (if one is needed) who can and will observe and report the patient's status
  • Pre-study clinical laboratory findings within normal range or, if outside of 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 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
  • 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
  • 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.

Who cannot join

  • 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
  • Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study
  • Body Mass Index (BMI) of 19.0 kg/m2 or lower
  • Unwilling to discontinue tizanidine and theophylline-containing medications during study participation
  • Serum chloride < 100 mmol/L
  • Neurological impairment due to a condition other than ALS, including history of transient ischemic attack (TIA) within the past year
Show all 9Show fewer
  • 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
  • Has taken any investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
  • Previously received CK-2017357 in any previous clinical trial

Trial locations and contacts

75 sites in 8 countries.

75 sites in 8 countries

United States44 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University, School of Medicine

    Atlanta, Georgia, 30322

  • Georgia Health Sciences University

    Augusta, Georgia, 30912

  • Johns Hopkins University

    Baltimore, Maryland, 21205

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Carolinas Medical Center Department of Neurology

    Charlotte, North Carolina, 27406

  • University of Virginia

    Charlottesville, Virginia, 22908

  • Ohio State University Department of Neurology

    Columbus, Ohio, 43221

  • Texas Neurology

    Dallas, Texas, 75214

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke University

    Durham, North Carolina, 27705

  • St Mary's Healthcare

    Grand Rapids, Michigan, 49503

  • Penn State Hershey Neuroscience Clinics

    Hershey, Pennsylvania, 17033

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University Department of Neurology

    Indianapolis, Indiana, 46202

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Mayo Clinic Florida Department of Neurology

    Jacksonville, Florida, 32224

  • University of Kansas

    Kansas City, Kansas, 66160

  • University of California, San Diego

    La Jolla, California, 92093

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Neurology Associates

    Lincoln, Nebraska, 68506

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Hennepin County Medical Center - Berman Center for Research

    Minneapolis, Minnesota, 55415

  • West Virginia University Department of Neurology

    Morgantown, West Virginia, 26506

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Hospital for Special Care

    New Britain, Connecticut, 06053

  • Hospital for Special Surgery

    New York, New York, 10021

  • UC Irvine ALS & Neuromuscular Center

    Orange, California, 92868

  • Drexel Neurology

    Philadelphia, Pennsylvania, 19107

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19107

  • Barrow Neurology

    Phoenix, Arizona, 85013

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Providence ALS Center

    Portland, Oregon, 97213

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Rochester

    Rochester, New York, 14642

  • UTHSCSA Department of Neurology

    San Antonio, Texas, 78229

  • Coordinated Clinical Research

    San Diego, California, 92103

  • California Pacific Medical Center Forbes Norris MDA/ALS Research Center

    San Francisco, California, 94115

  • Saint Louis University

    St Louis, Missouri, 63104

  • Washington University

    St Louis, Missouri, 63110

  • SUNY Upstate Medical University

    Syracuse, New York, 13120

  • The George Washington University

    Washington D.C., District of Columbia, 20037

  • Wake Forest University, School of Medicine

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

Canada12 sites

  • Heritage Medical Research

    Calgary, Alberta, T2N 4Z6

  • University of Alberta Hospital

    Edmonton, Alberta, B3H 3A7

  • Stan Cassidy Centre for Rehabilitation

    Fredericton, New Brunswick, E3B 0C7

  • QE II Health Sciences Centre

    Halifax, Nova Scotia, B3H 3A7

  • McMaster University Medical Centre

    Hamilton, Ontario, L8S 4K1

  • Queen's University : Kingston General

    Kingston, Ontario, K7L 2V7

  • London Health Sciences

    London, Ontario, N6A 5A5

  • Hôpital Notre Dame (CHUM) Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2L4M1

  • Montreal Neurological Institute

    Montreal, Quebec, H3A 2B4

  • CHU de Quebec: Hopital l'Enfant-Jesus

    Québec, Quebec, G1J 1Z4

  • Univ. of Toronto - Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • University of British Columbia

    Vancouver, British Columbia, V5Z 2G9

Other trials in Canada

France7 sites

  • CHRU de Lille - Hôpital Roger Salengro

    Lille, F-59037 LILLE cedex

  • CHU de Limoges - Hôpital Dupuytren

    Limoges, 87042 LIMOGES CEDEX

  • Hôpital La Timone Adulte

    Marseille, 13005

  • CHU Montepellier

    Montpellier, 34295 Montpellier Cedex 5

  • Hôpital Archet 1

    Nice, 06602

  • Hôpital de la Salpêtrière

    Paris, Cedex 13

  • Hôpital Bretonneau

    Tours, 37000

Other trials in France

United Kingdom6 sites

  • Walton Centre for Neurology and Neurosurgery

    Liverpool, L9 7LJ

  • Kings College Hospital NHS Foundation Trust

    London, SE5 8AF

  • John Radcliffe Hospital

    Oxford, OX3 9DU

  • Plymouth Hospitals NHS Trust

    Plymouth, PL6 8DH

  • Sheffield Institute for Translational Neuroscience

    Sheffield, S10 2HQ

  • Barts and the London MND & the Centre Royal London Hospital

    Whitechapel, London

Other trials in United Kingdom

Germany3 sites

  • Charite Universitätsmedizin

    Berlin, 13353

  • Hannover Medical School

    Hanover, 30625

  • University of Ulm

    Ulm, 89081

Other trials in Germany

Ireland1 site

  • Trinity College, Beaumont Hospital

    Dublin, 9

Other trials in Ireland

Netherlands1 site

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Spain1 site

  • Hospital Carlos III

    Madrid, 28029

Other trials in Spain

About this study

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)

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).

Read the 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 who tolerate the open-label 125 mg of CK-2017357 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.

Being tested
CK-2017357, Placebo tablets, Riluzole
Medical subject headings
Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CK-2017357Drug

    Also called tirasemtiv

    CK-2017357 125 mg tablets twice daily

  • Placebo tabletsOther

    Tablets

  • RiluzoleDrug

    Also called Rilutek

    Tablets

Study groups in NCT01709149
Study groupRoleWhat they receive
CK-2017357Experimental125 mg tablets
Receives: Drug: CK-2017357; Drug: Riluzole
PlaceboPlacebo comparatorPlacebo tablets
Receives: Other: Placebo tablets; Drug: Riluzole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Change From Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Total Score to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

    The ALSFRS-R is used to measure the progression and severity of disease; it consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in 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.

    Measured: Baseline, 8 weeks, 12 weeks

Secondary outcomes (6)

  1. Change From Baseline in Maximum Voluntary Ventilation (MVV) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

    MVV was measured as the volume (in liters) of air that could be exhaled during 12 seconds of rapid deep breathing; for analysis purposes, the measured volume was extrapolated to 1 minute (to give units of L/min).

    Measured: Baseline, 8 weeks, 12 weeks

  2. Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

    SNIP was measured at functional residual capacity, the bottom of the tidal breathing cycle, through 1 plugged nostril while the other remained open. Inspiratory pressure is a negative number where a larger negative number represents . . . A forceful, maximal inspiratory sniff was performed and a peak pressure value reported. The best result (ie, the highest number) from 5 tests was recorded as the SNIP.

    Measured: Baseline, 8 weeks, 12 weeks

  3. Change From Baseline in Slow Vital Capacity (SVC) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

    SVC was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, the 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 % predicted values (ie, the test result as a percent of predicted values for the patients of similar demographic and baseline characteristics [eg, height, age, sex]).

    Measured: Baseline, 8 weeks, 12 weeks

  4. Change From Baseline in Maximum Handgrip Strength in the Weaker Hand to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

    Maximum handgrip strength was measured using an electronic hand dynamometer; patients were asked to squeeze the device with the maximum possible force.

    Measured: Baseline, 8 weeks, 12 weeks

  5. Change From Baseline in Handgrip Fatigability (at 60% of Target in the Weaker Hand) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

    Handgrip fatigability was measured immediately following determination of maximum handgrip strength (via an electronic hand dynamometer). Once maximum handgrip strength was achieved, the force of the grip was timed for 2 minutes or until the grip strength had dropped to 60% of the maximum, whichever came first.

    Measured: Baseline, 8 weeks, 12 weeks

  6. Change From Baseline in Muscle Strength Mega-Score Based on Percent Change in Muscle Strength Measurements to the Average at the End of Weeks 8 and 12 of Double-blind Treatment

    A hand-held dynamometer (HHD), 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 (bilateral), wrist extension (bilateral), knee extension (bilateral), and ankle dorsiflexion (bilateral). For each assessment time point, the percent change from baseline was calculated for each muscle group and handgrip strength. The muscle strength mega-score was calculated as the average of the changes (ie, percent change from baseline) observed for each muscle groups as well as handgrip strength. For this endpoint, negative values indicate a decline in muscle strength.

    Measured: Baseline, 8 weeks, 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionMar 2014
  4. Study completionMar 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
711 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01709149
Sponsor's protocol ID
CY 4026
Status last verified
Mar 2020
First submitted
16 Oct 2012
Last updated
31 Mar 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CK-2017357 and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 75 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United States, Canada, France, United Kingdom, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Change From Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Total Score to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment (time frame: Baseline, 8 weeks, 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01709149.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in