A Study of CK-2127107 in Patients With Spinal Muscular Atrophy
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|ClinicalTrials.gov Identifier: NCT02644668|
Recruitment Status : Completed
First Posted : January 1, 2016
Last Update Posted : May 15, 2020
|Condition or disease||Intervention/treatment||Phase|
|Spinal Muscular Atrophy||Drug: Placebo Drug: Reldesemtiv 150 mg Drug: Reldesemtiv 450 mg||Phase 2|
CY 5021 was a Phase 2, double-blind, randomized, placebo-controlled, multiple dose study of reldesemtiv in 2 sequential ascending dose cohorts of patients with SMA. Patients were randomized 2:1 to receive reldesemtiv or placebo twice daily for 8 weeks. Patients randomized to reldesemtiv in Cohort 1 received a dose of 150 mg twice daily and patients randomized to reldesemtiv in Cohort 2 received 450 mg twice daily. Within each cohort, randomization was stratified by ambulatory status (ambulatory versus non ambulatory).
The primary objective of the study was to determine the PD effects of reldesemtiv on measures of pulmonary function, respiratory function, muscle strength, and motor function. Other PD measures included changes in the timed up and go (TUG) test, a 6-minute walk test (6MWT), and patient and investigator global assessments. Secondary objectives included safety of multiple doses of reldesemtiv and an evaluation of the pharmacokinetics of reldesemtiv.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Study of CK-2127107 in Two Ascending Dose Cohorts of Patients With Spinal Muscular Atrophy|
|Actual Study Start Date :||January 14, 2016|
|Actual Primary Completion Date :||May 31, 2018|
|Actual Study Completion Date :||May 31, 2018|
Placebo Comparator: Placebo
Patients randomized to this treatment arm received a placebo suspension twice daily for 8 weeks.
Granules for oral suspension (placebo)
Experimental: Reldesemtiv 150 mg twice daily
Patient randomized to this treatment arm received reldesemtiv suspension at a dose of 150 mg, twice daily for 8 weeks.
Drug: Reldesemtiv 150 mg
Granules for oral suspension, 18.7% reldesemtiv
Other Name: CK-2127107
Experimental: Reldesemtiv 450 mg twice daily
Patients randomized to this treatment arm received reldesemtiv suspension at a dose of 450 mg, twice daily for 8 weeks.
Drug: Reldesemtiv 450 mg
Granules for oral suspension, 56.0% reldesemtiv
Other Name: CK-2127107
- Change from Baseline to Week 8 in Percent Predicted Forced Vital Capacity (FVC) [ Time Frame: 8 weeks ]FVC was measured using a calibrated spirometer (in units of liters). Patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). Values obtained were converted to percent predicted values (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics [eg, height, age, sex]).
- Change from Baseline to Week 8 in Maximum Inspiratory Pressure (MIP) [ Time Frame: 8 weeks ]MIP was measured (in units of cm H20) using a calibrated spirometer with an inspiratory pressure valve attached. For the test, patients were asked to inhale as forcefully as possible, to their maximum pressure.
- Change from Baseline to Week 8 in Maximum Expiratory Pressure (MEP) [ Time Frame: 8 weeks ]MEP was measured (in units of cm H20) using a calibrated spirometer with an exspiratory pressure valve attached. For the test, patients were asked to maximally inhale then perform a forced exhalation with as forcefully as possible.
- Change from Baseline to Week 8 in Muscle Strength Mega-Score [ Time Frame: 8 weeks ]
Muscle strength of 3 muscle groups (elbow flexion, knee extension, and shoulder abduction) were measured bilaterally using a hand-held dynamometer. Muscle strength was measured twice for each body location; if the variability between the 2 measures was > 15%, a third measure was obtained.
The maximum muscle strength of the 2 measurements was identified and transformed as a percent change from baseline using the equation: ([postbaseline value - baseline value] / baseline value) × 100.
The mega-score was a composite score that averaged strength across the 3 muscle groups. It was calculated as the mean of the non-missing transformed muscle strength scores among the 3 muscle groups each measure bilaterally (totaling 6 body locations).
- Change from Baseline to Week 8 in the Hammersmith Functional Motor Scale-Expanded (HFMS-E) [ Time Frame: 8 weeks ]The HFMS-E evaluated the level of independent mobility and motor skills through assessment of 33 test-items, each scored from 0 (worse) to 2 (better). The total score was calculated as the sum of the scores among the 33 test items, and has a range from 0 to 66.
- Change from Baseline to Week 8 in Revised Upper Limb Module (RULM) [ Time Frame: 8 weeks ]The RULM assessed motor function in the upper limbs (specifically shoulder, elbow, wrist, and hand function) that related to activities of everyday life. The RULM consisted of 20 items, 1 of which was scored on a 7-point scale (from 0 to 6) and the remaining 19 were scored on a 3-point scale (from 0 to 2); the higher the total score, the better the function.
- Change from Baseline to Week 8 in the TUG Test [ Time Frame: 8 weeks ]The TUG test measured the time (in seconds) it took for a patient to rise from a chair, walk 3 meters, turn around, walk back to the chair and sit down.
- Change from Baseline to Week 8 in the 6MWT [ Time Frame: 8 weeks ]The 6MWT measured the distance (in meters) a patient walked in 6 minutes.
- Patient Global Assessment: Proportion of Patients with an Improvement [ Time Frame: 8 weeks ]The patient assessed whether they felt the same, better, or worse than prior to dosing on Day 1.
- Investigator Global Assessment: Proportion of Patients with an Improvement [ Time Frame: 8 weeks ]The Investigator assessed whether patient appeared the same, better, or worse than prior to dosing on Day 1.
- Reldesemtiv maximum observed plasma concentration (Cmax) [ Time Frame: End of Week 8 ]Determined by evaluation of reldesemtiv plasma concentrations from blood samples collected prior to dosing and at 1, 3, and 6 hours following dosing
- Reldesemtiv area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12) [ Time Frame: End of Week 8 ]Determined by evaluation of reldesemtiv plasma concentrations from blood samples collected prior to dosing and at 1, 3, and 6 hours following dosing
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02644668
|Study Director:||MD, Cytokinetics||Cytokinetics, Inc.|