Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis

September 18, 2019 updated by: Cytokinetics

A Phase II, Double-Blind, Randomized, Three-Way Crossover, Placebo-Controlled, Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis on Standard Therapy

The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized myasthenia gravis (MG).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a Phase II, double-blind, randomized, three-way crossover, placebo-controlled, PD study of CK-2017357 in patients with generalized MG on standard therapy. 36 to 78 patients will be randomized at approximately 15 study centers to one of six different treatment sequences. Each treatment sequence consists of three dosing periods in which patients receive single oral doses of placebo, 250 mg, and 500 mg of CK-2017357. All six treatment sequences will enroll 6 patients. A wash out period of at least 7 days (to a maximum of 10 days) will be employed between the individual doses for each patient. This study is designed to assess the effects of CK-2017357 on the standardized Quantitative Myasthenia Gravis (QMG) score, Manual Muscle Test, Myasthenia Gravis Composite Assessment (MGCA) and Forced Vital Capacity. The pharmacokinetic (PK) and pharmacodynamic (PD) relationship of CK-2017357 after two single doses will be assessed versus placebo.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Fresno, California, United States, 93721
        • UCSF - Fresno
      • Orange, California, United States, 92868
        • University of California - Irvine
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center
      • Stanford, California, United States, 94305
        • Stanford University
    • Connecticut
      • New Britain, Connecticut, United States, 06053
        • Hospital For Special Care
    • Kansas
      • Kansas City, Kansas, United States, 26506
        • The University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins
    • Massachusetts
      • Newton, Massachusetts, United States, 02459
        • Neurocare Center for Research
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Drexel University College of Medicine
      • Pittsburgh, Pennsylvania, United States, 15212
        • West Penn Allegheny Health System
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Ability to comprehend and willing to sign an Informed Consent Form (ICF)
  • Ability to understand written and oral English language
  • Males and females between 18 and 80 years of age, inclusive
  • Patient's signs and symptoms not better explained by another disease process
  • Established diagnosis of MG defined as clinical evidence of muscle weakness and positive AChR-binding antibody titer (>0.02 nmol/L)
  • Myasthenia Gravis Foundation of America (MGFA) clinical classification II or III
  • Stable MG disease for 4 weeks prior to randomization
  • Ability to refrain from IVIg treatments during the course of the study
  • Ability to refrain from cholinesterase-inhibitors (e.g. pyridostigmine) for 12 hours before each dose
  • Ability to perform all elements of the QMG
  • Grade of 2 or 3 in two or more of the following muscle groups as measured by QMG: right or left arm flexion, head lift, and right or left leg raise at 45° Note: Patients may re-screen if they fail due to inadequate weakness from taking pyridostigmine within 12 hours of screening
  • Body mass index (BMI) of 18.0 to 36.0 kg/m2, inclusive
  • Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [CPK]) within the normal range, or if outside of the normal range, deemed not clinically significant by the Investigator
  • For female patients only: Agreement to use a double barrier during sexual intercourse (1 hormonal, plus 1 barrier method, or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures)
  • For male patients only: Agreement either 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) for the duration of the study and 10 weeks after the end of the study or to abstain from sexual intercourse for the duration of the study and 10 weeks after the end of the study

Exclusion criteria:

  • History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue
  • Other major chronic or debilitating illnesses within six months prior to study entry
  • Hepatic insufficiency (defined as ALT or AST > 3x ULN, or total bilirubin > 3 mg/dL)
  • Renal insufficiency (defined as serum creatinine > 2.5 mg/dL or receiving dialysis)
  • Other myasthenic syndromes (e.g. Lambert Eaton syndrome; inherited myasthenic syndrome)
  • Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures)
  • Receipt of IVIg or plasmapheresis treatment within 6 weeks prior to the first dose of study drug
  • Changes to immunosuppressive treatments (i.e., prednisone) within 6 weeks prior to the first dose of study drug
  • Rituxan treatment within 3 months prior to study entry
  • Participation in any other investigational study drug or device trial in which receipt of an investigational study drug or device occurred within 30 days prior to dosing
  • Any prior treatment with CK-2017357
  • Recent history of alcoholism or drug abuse, or significant behavioral or psychiatric problems, or other conditions which in the Investigator's opinion may impair ability to adequately comply with the requirements of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemitiv
Experimental: Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemitiv
Experimental: Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemitiv
Experimental: Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemitiv
Experimental: Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemitiv
Experimental: Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
  • tirasemitiv

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Quantitative Myasthenia Gravis score (QMG)
Time Frame: 1 day
A quantitative motor assessment of muscular weakness on a scale of 0 to 3 with 0 representing "none" and 3 representing "severe". Muscular assessments included in the overall score are effects on double vision, ptosis, facial muscles, swallowing, speech, outstretched arms and legs, forced vital capacity, hand grip strength, and ability to lift head.
1 day
Pulmonary Function Test (VC in liters)
Time Frame: 1 day
Forced Vital Capacity
1 day
Manual Muscle Test (MMT)
Time Frame: 1 day
Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
1 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events
Time Frame: 4 weeks
4 weeks
Characterize dose and plasma concentrations of CK-2017357 and QMG
Time Frame: 2 days
2 days
Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)
Time Frame: 2 days
2 days
Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)
Time Frame: 2 days
2 days
Modified MG Symptom Score
Time Frame: 2 days
Patients will be asked questions regarding five myasthenia gravis systems including trouble using eyes, trouble eating, difficulty speaking, trouble walking and trouble performing personal grooming needs. Each of the areas is scored 0 (none at all) to 3 (very much) and the overall score combining the score of all five areas on a scale of 0 to 15 with 0 being normal and 15 being severe weakness
2 days
Patient Global Assessment
Time Frame: 2 days
Patients answer a single question as to whether they feel the same, better or worse as compared to how they felt pre-dose
2 days
Investigator Global Assessment
Time Frame: 2 days
Investigator answer a single as question as to whether they think the patient appears the same, better or worse as compared to the patient's status at pre-dose
2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cytokinetics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Andrew Wolff, MD, FACC, Cytokinetics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 28, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 29, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 30, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 24, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CY 4023
  • 1RC3NS070670-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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