Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv
Brief summary
The purpose of this study is to assess the long-term safety and tolerability of reldesemtiv in patients with ALS who have successfully completed dosing in the Phase 3 clinical trial, CY 5031 (also known as COURAGE-ALS)
Detailed description
CY 5032 is an open-label extension (OLE) study of the selective fast skeletal muscle troponin activator, reldesemtiv, in patients with ALS who finished dosing (through Week 48) in CY 5031 (COURAGE-ALS). Approximately 400 patients from the sites that participated in CY 5031 are expected to be enrolled in the open-label extension, CY 5032. Following enrollment, patients will continue dosing with reldesemtiv, 300 mg twice a day for a 600 mg total daily dose (TDD) for a period of 48 weeks. At the end of 48 weeks, patients may transition to a reldesemtiv Managed Access Program (MAP) if the treating physician agrees to participate in the program.
Interventions
DRUGReldesemtiv
Oral tablet
Sponsors
Cytokinetics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to comprehend and willing to sign an ICF and willing to comply with all study procedures and restrictions for the duration specified in the Schedule of Activities. If non-written consent is given, a Legal Designee of the patient must sign the ICF form. * Completed dosing in CY 5031
Exclusion criteria
* Has taken investigational study drug (other than reldesemtiv) prior to dosing, within 30 days or five half-lives of the prior agent, whichever is greater * Presence on Day 1 of any medically significant cardiac, pulmonary, gastrointestinal, 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. * Use of a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days prior to first dose of reldesemtiv in CY 5032 or a strong CYP3A4 inducer within 14 days prior to first dose of reldesemtiv in CY 5032 * Use of a medication that is an OCT1/OCT2 substrate within 7 days prior to first dose of reldesemtiv in CY 5032 * Currently participating in another trial, managed access program, open label extension, early access program, or through the right to try act is receiving an investigational drug or received an investigational drug or device within 30 days (or 5 half-lives for drugs, whichever is longer) prior to Day 1. Patients also cannot be taking outside of a clinical trial certain investigational drugs (which includes drugs, supplements, and nutraceuticals) that are currently being studied or have been studied for the treatment of ALS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Safety and Tolerability | Baseline to Week 34 (time the study was terminated prematurely) | Incidence of treatment-emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Effect of Reldesemtiv on ALSFRS-R Functional Outcomes | Baseline to Week 32 (last timepoint before study was terminated prematurely) | Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total scores. ALSFRS-R total score range is from 0 to 48. A score of 48 reflects normal function. |
Countries
Australia, Belgium, Canada, Ireland, Italy, Netherlands, Spain, Sweden, United States
Participant flow
Recruitment details
Participants were enrolled from 41 trial centers in North America, Europe, and Australia. The first participant was enrolled on 04 Aug 2022 and the last participant completed on 07 Jun 2023.
Pre-assignment details
A total of 71 participants who were previously enrolled in the double-blind placebo-controlled CY 5031 parent trial were enrolled in this trial and received at least one dose of reldesemtiv.
Participants by arm
| Arm | Count |
|---|---|
| Reldesemtiv Participants in this arm take 1 reldesemtiv 300 mg oral tablet twice a day for a 600 mg total daily dose (TDD)
Reldesemtiv: Oral tablet | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Participant removed at Sponsor request | 1 |
| Overall Study | Trial terminated | 61 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Reldesemtiv |
|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 11.62 |
| ALSFRS-R Total Score | 29.8 scores on a scale STANDARD_DEVIATION 8.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Percent Predicted Forced Vital Capacity | 70.6 percent predicted STANDARD_DEVIATION 22.76 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized White | 65 Participants |
| Region of Enrollment Australia | 8 Participants |
| Region of Enrollment Europe | 10 Participants |
| Region of Enrollment North America | 53 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 40 Participants |
| Time Since ALS Diagnosis at Screening in CY 5031 | 17.9 months STANDARD_DEVIATION 4.69 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 71 |
| other Total, other adverse events | 27 / 71 |
| serious Total, serious adverse events | 11 / 71 |
Outcome results
Primary
Long-term Safety and Tolerability
Incidence of treatment-emergent adverse events
Time frame: Baseline to Week 34 (time the study was terminated prematurely)
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reldesemtiv | Long-term Safety and Tolerability | 39 Participants |
Secondary
Long-term Effect of Reldesemtiv on ALSFRS-R Functional Outcomes
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total scores. ALSFRS-R total score range is from 0 to 48. A score of 48 reflects normal function.
Time frame: Baseline to Week 32 (last timepoint before study was terminated prematurely)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reldesemtiv | Long-term Effect of Reldesemtiv on ALSFRS-R Functional Outcomes | Week 12 | 29.5 score on a scale | Standard Deviation 9.04 |
| Reldesemtiv | Long-term Effect of Reldesemtiv on ALSFRS-R Functional Outcomes | Week 24 | 27.4 score on a scale | Standard Deviation 11.86 |
| Reldesemtiv | Long-term Effect of Reldesemtiv on ALSFRS-R Functional Outcomes | Week 32 | 26.6 score on a scale | Standard Deviation 13.96 |