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).
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
32
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
500 mg CK-2017357 in capsules administered as a single oral dose.
UCSF - Fresno
Fresno, California, United States
University of California - Irvine
Orange, California, United States
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.
Time frame: 1 day
Pulmonary Function Test (VC in liters)
Forced Vital Capacity
Time frame: 1 day
Manual Muscle Test (MMT)
Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
Time frame: 1 day
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
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
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California Pacific Medical Center
San Francisco, California, United States
Stanford University
Stanford, California, United States
Hospital for Special Care
New Britain, Connecticut, United States
The University of Kansas Medical Center
Kansas City, Kansas, United States
Johns Hopkins
Baltimore, Maryland, United States
Neurocare Center for Research
Newton, Massachusetts, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Duke University
Durham, North Carolina, United States
...and 5 more locations
Time frame: 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
Time frame: 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
Time frame: 2 days