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A Study of CK-2127107 in Patients With Spinal Muscular Atrophy

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Cytokinetics
Sponsor:
Collaborator:
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
Cytokinetics
ClinicalTrials.gov Identifier:
NCT02644668
First received: December 23, 2015
Last updated: August 17, 2017
Last verified: August 2017
  Purpose
The primary objective of this study is to demonstrate a pharmacodynamic effect of CK-2127107 on measures of skeletal muscle function or fatigability in patients with Spinal Muscular Atrophy Types II-IV.

Condition Intervention Phase
Spinal Muscular Atrophy Drug: CK-2127107 150 mg Drug: Placebo Drug: CK-2127107 450 mg Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Study of CK-2127107 in Two Ascending Dose Cohorts of Patients With Spinal Muscular Atrophy (SMA)

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Change from baseline and slope of change from baseline in Forced Vital Capacity (FVC) [ Time Frame: 8 weeks ]
  • Change from baseline and slope of change from baseline in Maximum Inspiratory Pressure (MIP)/Maximum Expiratory Pressure (MEP) [ Time Frame: 8 weeks ]
  • Change from baseline and slope of change from baseline in Hand-Held Dynamometry (HHD) [ Time Frame: 8 weeks ]
  • Change from baseline and slope of change from baseline in Hammersmith Functional Motor Scale-Expanded (HFMS-E) [ Time Frame: 8 weeks ]
  • Change from baseline and slope of change from baseline in Revised Upper Limb Module (RULM) [ Time Frame: 8 weeks ]
  • Change from baseline and slope of change from baseline in Timed Up and Go (TUG) test [ Time Frame: 8 weeks ]
  • Change from baseline and slope of change from baseline in 6-Minute Walk Test (6MWT) [ Time Frame: 8 weeks ]
  • Global Assessments [ Time Frame: End of Week 2, End of Week 8 and End of Week 12 follow-up visit ]
    Patient will be asked whether they feel the same, better or worse as compared to how they felt pre-dose on Day 1. Investigator will assess whether patient appears the same, better or worse as compared to patient's status at pre-dose on Day 1.


Secondary Outcome Measures:
  • Safety and tolerability of multiple doses of CK-2127107 administered orally to SMA patients (TEAEs, SAEs, discontinuations due to TEAEs, medical history, physical and neurological examinations, ECGs, vital signs, clinical safety labs) [ Time Frame: 8 weeks ]
    Safety will be assessed by recording and monitoring all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and additional assessments will include regular measurement of medical history, physical and neurological examinations, ECGs, and vital signs, and regular monitoring of clinical safety labs, including complete blood count and white blood count with differential, serum chemistries and urinalysis,

  • Maximum observed plasma concentration (Cmax) of CK-2127107 [ Time Frame: 1 and 3 hours post-dose at Day 1 and End of Week 2 and 1, 3 and 6 hours at End of Week 8 ]
  • Pre-dose plasma concentration (Ctrough) of CK-2127107 [ Time Frame: Pre-dose at Day 1, End of Weeks 1, 2, 4 and 8 ]
  • Area under the plasma concentration-time curve from pre-dose to the last measurable plasma concentration (AUC0-t) of CK-2127107 [ Time Frame: Pre-dose, 1 and 3 hours post-dose at Day 1, End of Week 2 and pre-dose, 1, 3 and 6 hours post-dose at End of Week 8 ]
  • Area under the plasma concentration-time curve at steady-state will be the average of AUC0-24 at the end of Weeks 2 and 8 (AUCavg) of CK-2127107 [ Time Frame: Pre-dose, 1 and 3 hours post-dose at End of Week 2 and pre-dose, 1, 3, and 6 hours post-dose at End of Week 8 ]

Estimated Enrollment: 72
Study Start Date: December 2015
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1/Ambulatory/CK-2127107/Placebo
18 ambulatory patients ≥ 12 years of age with Type III or Type IV SMA randomized 2:1 to CK-2127107 150 mg versus placebo single dose on Day 1 and then twice daily (BID) for remainder of 8 weeks
Drug: CK-2127107 150 mg Drug: Placebo
Experimental: Cohort 1/Non-Ambulatory/CK-2127107/Placebo
18 non-ambulatory patients ≥ 12 years of age with Type II or Type III SMA randomized 2:1 to CK-2127107 150 mg versus placebo single dose on Day 1 and then twice daily (BID) for remainder of 8 weeks
Drug: CK-2127107 150 mg Drug: Placebo
Experimental: Cohort 2/Ambulatory/CK-2127107/Placebo
18 ambulatory patients ≥ 12 years of age with Type III or Type IV SMA randomized 2:1 to CK-2127107 450 mg versus placebo single dose on Day 1 and then twice daily (BID) for remainder of 8 weeks
Drug: Placebo Drug: CK-2127107 450 mg
Experimental: Cohort 2/Non-Ambulatory/CK-2127107/Placebo
18 non-ambulatory patients ≥ 12 years of age with Type II or Type III SMA randomized 2:1 to CK-2127107 450 mg versus placebo single dose on Day 1 and then twice daily (BID) for remainder of 8 weeks
Drug: Placebo Drug: CK-2127107 450 mg

Detailed Description:
This is the first study being conducted in these patients and is designed to assess the effect of 8 weeks of dosing of CK-2127107 on measures of muscle function in both ambulatory and non-ambulatory patients with SMA. The plasma concentration of CK-2127107 will be measured at selected time points during the course of dosing and the plasma concentrations obtained in this study may be used to conduct exposure-response analysis.
  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to comprehend and willing to sign an Informed Consent Form (ICF) for patients 18 years of age and older. For patients less than 18 years of age, parent(s)/legal guardian(s) of patients must provide written informed consent prior to participation in the study and informed assent will be obtained from minors at least 12 years of age when required by regulation.
  • Males or females with genetically confirmed diagnosis of SMA who are Type II, III or IV and at least 12 years of age
  • Ambulatory patients, once having achieved a standing position independently, must be able to complete at least one lap in the 6-minute walk test (at least 50 meters) within 6 minutes without assistance.
  • Non-ambulatory patients (defined as individuals who are effectively requiring a wheelchair for all mobility needs; they may be able to stand or walk short distances, but unable to walk 50 meters without assistance in 6 minutes). Non-ambulatory patients must be able to tolerate an upright sitting position, with support, continuously for 3 hours
  • Hammersmith (HFMS-E) score ≥ 10 and ≤ 54
  • Contracture of the elbow flexion and knee flexion ≤ 90 degrees
  • Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
  • Able to swallow an oral suspension and in the opinion of the Investigator, is expected to continue to be able to do so for the duration of the trial. Administration via a feeding tube is not allowed.
  • Forced vital capacity (FVC) > 20% predicted
  • Male patients who have reached puberty must agree to do either of the following from Screening until 10 weeks after the last dose of the investigational product unless they have had a vasectomy and confirmed sperm count is zero:

    • Abstain from sexual intercourse, OR
    • If having heterosexual intercourse, must use a condom and their female partners who are of childbearing potential must use a highly effective contraception method*
  • Female patients who have had their first period will be considered of childbearing potential unless they are anatomically and physiologically incapable of becoming pregnant. If of childbearing potential, the female patients must:

    • Have a negative urine/serum pregnancy test at Screening AND
    • Abstain from heterosexual intercourse from Screening until 10 weeks after the last dose of investigational product OR
    • If having heterosexual intercourse, must use a highly effective contraception method* and require the male partners to use a condom from Screening until 10 weeks after the last dose of investigational product

      *Highly effective contraception methods include:

    • Established use of oral, injected or implanted hormonal methods of contraception
    • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Male patients must agree to refrain from sperm donation from Screening until 10 weeks after the final study drug administration

Exclusion Criteria:

  • History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
  • Hospitalization within 2 months of Screening
  • History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
  • A clinically significant illness within 4 weeks of Screening
  • History of alcoholism or drug addiction within 2 years prior to Screening
  • History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to Screening
  • Patient has used a strong CYP3A4 inhibitor within 7 days prior to first dose of study drug or a strong CYP3A4 inducer within 14 days prior to first dose of study drug
  • Any other medical condition that would interfere with performance of testing including (but not limited to) significant joint pain or arthritis limiting mobility, and chronic neuromuscular pain sufficient to require ongoing analgesic medication
  • Participation by two people at the same time that are living in the same household
  • Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days or five half-lives of the other investigational study drug, whichever is greater, prior to Screening
  • An ALT or AST greater than 2-fold the upper limit of normal (ULN) or has total bilirubin greater than the ULN at screening. These assessments may be repeated once at the investigator's discretion (within the screening window)
  • Currently taking nusinersen, or has taken it in the past, or plans to take it during the course the study
  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: NCT02644668

Contacts
Contact: MD Cytokinetics medicalaffairs@cytokinetics.com

Locations
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Katrina Nguyen    310-825-3264    katrinanguyen@mednet.ucla.edu   
Pediatric Neuromuscular Clinic Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Angelica Martinez    650-725-4341    ammarti1@stanford.edu   
United States, Connecticut
Hospital for Special Care Recruiting
New Britain, Connecticut, United States, 06053
Contact: Agnes Koczon-Jaremko, MD    860-612-6356    bkoczon-jaremko@hfsc.org   
United States, Florida
Nemours Childrens Hospital Recruiting
Orlando, Florida, United States, 32827
Contact: Kristan Anderson    407-650-7165    kristan.anderson@nemours.org   
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Hannah Munson    312-227-2201    hmunson@luriechildrens.org   
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Ayla McCalley    913-945-9937    amccalley2@kumc.edu   
United States, Maryland
Johns Hopkins Hospital Institute for Clinical and Translational Research Pediatric Clinical Research Unit Recruiting
Baltimore, Maryland, United States, 21287
Contact: Agnes King Rennie    443-287-6294    aking2@jhmi.edu   
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Grace Ordonez    617-919-7384    grace.ordonez@childrens.harvard.edu   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Traci Christenson       christensont@neuro.wustl.edu   
United States, Ohio
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Louisa Mezache    614-685-3030    louisa.mezache@osumc.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Josh Zigmont    267-426-7161    zigmontj@email.chop.edu   
United States, Utah
The University of Utah, Clinical Neurosciences Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Nicole Rausch    801-585-9055    nicoler@genetics.utah.edu   
Contact: Tara Newcomb    801-581-3551    taran@genetics.utah.edu   
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Tiffany Haig    403-955-3192    tiffany.haig@albertahealthservices.ca   
Canada, British Columbia
Children's and Women's Health Centre of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Nela Martic    604-875-2345 ext 6549    nmartic3@cw.bc.ca   
Canada, Ontario
Children's Hospital - LHSC Recruiting
London, Ontario, Canada, N6A 4G5
Contact: Maysaa Assaf    519-685-8500 ext 75556    maysaa.assaf@lhsc.on.ca   
Canada, Quebec
Montreal Neurological Institute and Hospital Recruiting
Montreal, Quebec, Canada, H3A 2B4
Contact: Kristiana Salmon    514-398-1779    kristiana.salmon@mcgill.ca   
Contact: Victoria Eon    514-398-1688    victoria.eon@mcgill.ca   
Sponsors and Collaborators
Cytokinetics
Astellas Pharma Global Development, Inc.
Investigators
Study Director: MD, Cytokinetics Cytokinetics, Inc.
  More Information

Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT02644668     History of Changes
Other Study ID Numbers: CY 5021
Study First Received: December 23, 2015
Last Updated: August 17, 2017

Additional relevant MeSH terms:
Neuromuscular Manifestations
Neuromuscular Diseases
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on September 21, 2017