Cytokinetics CY 5021

Principal Investigator: Nicholas Johnson
Keywords: Spinal Muscular Atrophy , SMA Type 1 , SMA Type 2 , SMA Type 3 , Muscular Distrophy Department: Neurology
IRB Number: 00088102 Co Investigator: Russell Butterfield
Specialty: Neurology, Neurology, Neurology, Neurology, Neurology
Sub Specialties: Neuromuscular Diseases, General Neurology, Movement Disorders, Spinal Muscular Atrophy, Muscular Dystrophy
Recruitment Status: Not yet recruiting

Contact Information

Nicole Rausch
nicoler@genetics.utah.edu
801-585-9717

Brief Summary

This study will be divided into two separate cohorts:

Cohort 1

(Group 1) 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

(Group 2) 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

 

Cohort 2

(Group 1) 18 ambulatory patients ≥ 12 years of age with Type III or Type IV SMA randomized 2:1 to CK-2127107 450 mg (or lower) versus placebo single dose on Day 1 and then twice daily (BID) for remainder of 8 weeks

(Group 2) 18 non-ambulatory patients ≥ 12 years of age with Type II or Type III SMA randomized 2:1 to CK-2127107 450 mg (or lower) versus placebo single dose on Day 1 and then twice daily (BID) for remainder of 8 weeks

Within each cohort, the participant's randomization will be stratified by ambulatory status versus non-ambulatory status.

 

The primary objective of this study is to determine the potential pharmacodynamic (PD) effects of the study drug CK-2127107 dry granules which is administered by suspension after multiple oral doses in patients with SMA.

The secondary objectives of this study is to evaluate the efficacy and tolerability and pharmacokinetic effects of multiple doses of the study drug CK-2127107 administered orally to SMA patients. 

Detailed Description

This is a Phase 2, double-blind, randomized, placebo-controlled, multiple dose, study of CK-2127107 in two sequential ascending dose cohorts of patients with Type II, Type III, or Type IV SMA. Within each cohort, randomization will be stratified by ambulatory status versus non-ambulatory status. The CK-2127107 Granules for Oral Suspension will be constituted by the site pharmacy for patient use as an oral suspension. Seventy-two male or female patients (two cohorts of 36 patients each) will receive twice daily doses of CK-2127107 suspension for 8 weeks.

Inclusion Criteria

Inclusion Criteria
Patients who meet all of the following criteria may be included in the study:
1. 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.
2. Males or females with genetically confirmed diagnosis of SMA who are Type II, III or IV and at least 12 years of age
3. 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
4. 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

5. Forced vital capacity (FVC) > 20% predicted at screening 
6. Hammersmith Functional Motor Scale-Expanded (HFMS-E) score ≥ 10 and ≤ 54 at screening
7. Contracture of the elbow flexion and knee flexion ≤ 90 degrees
8. Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
9. 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.
10. 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*
11. 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)
12. Male patients must agree to refrain from sperm donation from Screening until 10 weeks after the final study drug administration

Exclusion Criteria

Exclusion Criteria
Any of the following will exclude potential patients from the study:
1. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
2. Hospitalization within 2 months of Screening
3. 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)
4. A clinically significant illness, including but not limited to cardiac, pulmonary, GI, musculoskeletal, or psychiatric illness, that might interfere with the patient’s ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data, within 4 weeks of Screening

5. History of alcoholism or drug addiction within 2 years prior to Screening
6. History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to Screening
7. 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
8. 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
9. Participation by two people at the same time that are living in the same household
10. Taking any other investigational study drug as a clinical trial participant, within 30 days or five half-lives, whichever is greater, prior to Screening

11. An ALT or AST greater than 2-fold the upper limit of normal (ULN) or has total bilirubin greater than the ULN at screening. There assessments may be repeated once at the investigator's discretion (within the screening window)

12. Currently taking nusinersen, or has taken it in the past, or plans to take it during the course of the study