Myasthenia GravisPhase 2NCT01268280
Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis
A Phase 2 study testing 250 mg CK-2017357 and 500 mg CK-2017357 in people with Myasthenia Gravis, run by Cytokinetics at 15 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- 250 mg CK-2017357 and 500 mg CK-2017357
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 15 sitesUnited States
- Study dates
- Dec 2010to Oct 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Johns Hopkins
Baltimore, Maryland, 21205
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Virginia Health System
Charlottesville, Virginia, 22908
Duke University
Durham, North Carolina, 27710
UCSF - Fresno
Fresno, California, 93721
Baylor College of Medicine
Houston, Texas, 77030
The University of Kansas Medical Center
Kansas City, Kansas, 26506
Hospital for Special Care
New Britain, Connecticut, 06053
Neurocare Center for Research
Newton, Massachusetts, 02459
University of California - Irvine
Orange, California, 92868
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19107
West Penn Allegheny Health System
Pittsburgh, Pennsylvania, 15212
University of Texas Health Science Center
San Antonio, Texas, 78229
California Pacific Medical Center
San Francisco, California, 94115
Stanford University
Stanford, California, 94305
About this study
Official title: 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).
Read the 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.
- Conditions
- Myasthenia Gravis
- Being tested
- Placebo, 250 mg CK-2017357, 500 mg CK-2017357
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357Drug
Also called tirasemtiv
250 mg CK-2017357 in capsules administered as a single oral dose.
500 mg CK-2017357Drug
Also called tirasemitiv
500 mg CK-2017357 in capsules administered as a single oral dose.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence 1 | Experimental | Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg Receives: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357 |
| Treatment Sequence 2 | Experimental | Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg Receives: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357 |
| Treatment Sequence 3 | Experimental | Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg Receives: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357 |
| Treatment Sequence 4 | Experimental | Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo Receives: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357 |
| Treatment Sequence 5 | Experimental | Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg Receives: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357 |
| Treatment Sequence 6 | Experimental | Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo Receives: Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantitative Myasthenia Gravis score (QMG)
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.
Measured: 1 day
Pulmonary Function Test (VC in liters)
Forced Vital Capacity
Measured: 1 day
Manual Muscle Test (MMT)
Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
Measured: 1 day
Secondary outcomes (7)
Characterize dose and plasma concentrations of CK-2017357 and QMG
Measured: 2 days
Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)
Measured: 2 days
Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)
Measured: 2 days
Number of patients with adverse events
Measured: 4 weeks
Modified MG Symptom Score
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
Measured: 2 days
Patient Global Assessment
Patients answer a single question as to whether they feel the same, better or worse as compared to how they felt pre-dose
Measured: 2 days
Investigator Global Assessment
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
Measured: 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Closed after complete treatment of 32 patients after 21 months' recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andrew Wolff, MD, FACC, Study director, Cytokinetics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01268280
- Sponsor's protocol ID
- CY 4023
- Other IDs
- 1RC3NS070670-01
- Status last verified
- Sep 2019
- First submitted
- 28 Dec 2010
- Last updated
- 24 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sanders DB, Rosenfeld J, Dimachkie M, Meng L, Malik FI. A Study to Evaluate Efficacy, Safety and Tolerability of Single Doses of Tirasemtiv in Patients with Myasthenia Gravis. 65th Annual Meeting of the American Academy of Neurology, San Diego, CA, March 2013
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01268280
- Acronym / sponsor ID
- CY 4023
- Conditions
- Myasthenia Gravis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed after complete treatment of 32 patients after 21 months' recruitment.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Dec 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 30 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence 1 | Experimental | Drug: Placebo, Drug: 250 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg |
| Treatment Sequence 2 | Experimental | Drug: Placebo, Drug: 250 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg |
| Treatment Sequence 3 | Experimental | Drug: Placebo, Drug: 250 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg |
| Treatment Sequence 4 | Experimental | Drug: Placebo, Drug: 250 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo |
| Treatment Sequence 5 | Experimental | Drug: Placebo, Drug: 250 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg |
| Treatment Sequence 6 | Experimental | Drug: Placebo, Drug: 250 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboMatching placebo in capsules administered as a single oral dose. | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6 |
| 250 mg CK-2017357Also: tirasemtiv250 mg CK-2017357 in capsules administered as a single oral dose. | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6 |
| 500 mg CK-2017357Also: tirasemitiv500 mg CK-2017357 in capsules administered as a single oral dose. | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6 |
Primary outcome
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.
Pulmonary Function Test (VC in liters)
Time frame: 1 day
Forced Vital Capacity
Manual Muscle Test (MMT)
Time frame: 1 day
Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
7 secondary outcomes
Characterize dose and plasma concentrations of CK-2017357 and QMG
Time frame: 2 days
Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)
Time frame: 2 days
Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)
Time frame: 2 days
Number of patients with adverse events
Time frame: 4 weeks
Modified MG Symptom Score
Time frame: 2 days
Patient Global Assessment
Time frame: 2 days
Investigator Global Assessment
Time frame: 2 days
Results and safety
The study was stopped early (reason given: Closed after complete treatment of 32 patients after 21 months' recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Results publicationSanders DB, Rosenfeld J, Dimachkie M, Meng L, Malik FI. A Study to Evaluate Efficacy, Safety and Tolerability of Single Doses of Tirasemtiv in Patients with Myasthenia Gravis. 65th Annual Meeting of the American Academy of Neurology, San Diego, CA, March 2013
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Wolff, MD, FACC study director
Cytokinetics, Inc.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 250 mg CK-2017357 and 500 mg CK-2017357 in people with Myasthenia Gravis, run by Cytokinetics at 15 sites in United States.
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 15 inclusion and 12 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: stopped early, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. 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. 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?
The study was stopped early (reason given: Closed after complete treatment of 32 patients after 21 months' recruitment.). Results are not available in the source record.
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?
Quantitative Myasthenia Gravis score (QMG) (time frame: 1 day). The study lists 3 primary outcomes in all. 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 NCT01268280, which also lists 1 linked publication.
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 24 Sep 2019.