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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01268280
• Date of registration: 28/12/2010
• Prospective Registration: No
• Primary sponsor: Cytokinetics
• Public title: Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis
• Scientific 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
• Date of first enrolment: December 2010
• Target sample size: 32
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01268280
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Andrew Wolff, MD, FACC
• Affiliation: Cytokinetics, Inc.

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myasthenia Gravis

Intervention(s)

Drug: 250 mg CK-2017357

Drug: 500 mg CK-2017357

Drug: Placebo

Primary Outcome(s)

Manual Muscle Test (MMT) [Time Frame: 1 day]

Quantitative Myasthenia Gravis score (QMG) [Time Frame: 1 day]

Pulmonary Function Test (VC in liters) [Time Frame: 1 day]

Secondary Outcome(s)

Modified MG Symptom Score [Time Frame: 2 days]

Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT) [Time Frame: 2 days]

Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC) [Time Frame: 2 days]

Number of patients with adverse events [Time Frame: 4 weeks]

Characterize dose and plasma concentrations of CK-2017357 and QMG [Time Frame: 2 days]

Investigator Global Assessment [Time Frame: 2 days]

Patient Global Assessment [Time Frame: 2 days]

Secondary ID(s)

CY 4023

1RC3NS070670-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Neurological Disorders and Stroke (NINDS)