Amyotrophic Lateral Sclerosis (ALS) MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Cytokinetics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria • Males or Females between the ages of 18 and 80 years of age, inclusive • Diagnosis of familial or sporadic ALS (defined as meeting the laboratory-supported probable, probable, or definite criteria for ALS according to the World Federation of Neurology El Escorial criteria published in 2000 [Brooks 2000]). Patients who meet the possible criteria are eligible if they have lower motor neuron findings; those who have purely upper motor neuron findings are ineligible. • First symptom of ALS = 24 months prior to screening. The qualifying first symptoms of ALS are limited to manifestations of weakness in extremity, bulbar, or respiratory muscles. Cramps, fasciculations, or fatigue should not be taken in isolation as a first symptom of ALS. • ALSFRS-R total score = 44 at screening. Patients with a total score of 45 or higher may be rescreened 60±7 days following the original screening date and be deemed eligible if their ALSFRS-R total score is = 44 or if their score is 2 or more points less than at initial screening. Such patients must continue to meet all other inclusion/exclusion criteria at the time of rescreening. • Upright FVC = 65.0% of predicted for age, height, sex and ethnicity at screening according to Global Lung Initiative equation • Able to perform reproducible pulmonary function tests defined as being able to perform FVC at screening with variability of the 2 highest raw values of less than 10% with a maximum of 5 trials permitted. Screening FVC results must be reviewed and approved by the central review process prior to randomization. • Must be either on riluzole for = 30 days prior to screening or have not taken it for at least 30 days prior to screening • Must have completed at least 2 cycles of edaravone at the time of screening or have not received it for at least 30 days prior to screening • Able to swallow whole tablets • Clinical laboratory findings within the normal range, or if outside the normal range, not deemed clinically significant by the Investigator, except as specifically indicated as laboratory exclusion Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 374 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 181
Exclusion criteria
Exclusion criteria: • eGFRCysC 1 mg/mg (113 mg/mmol) at screening • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3-times the upper limit of normal (ULN) • Total bilirubin (TBL), direct or indirect bilirubin above the ULN. • Cognitive impairment, related to ALS or otherwise that impairs the patient’s ability to understand and/or comply with study procedures and provide informed consent • Other medically significant neurological conditions that could interfere with the assessment of ALS symptoms, signs or progression. • Presence at screening 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 • Has a tracheostomy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of reldesemtiv versus placebo on functional outcomes in ALS. To assess the safety and tolerability of reldesemtiv compared to placebo.;Secondary Objective: • To assess the effect of reldesemtiv versus placebo on combined functional and survival outcomes in ALS • To assess the effect of reldesemtiv versus placebo on ventilatory function • To assess the effect of reldesemtiv versus placebo on quality of life • To assess the effect of reldesemtiv versus placebo on handgrip strength Exploratory Objective To assess the effect of reldesemtiv versus placebo on the progression of ALS;Primary end point(s): • Change from baseline to Week 24 in ALSFRS-R total score.;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Combined assessment of change in ALSFRS-R total score, time to onset of respiratory insufficiency, and survival time up to Week 24 • Change from baseline to Week 24 in the percent predicted FVC • Change from baseline to Week 24 in the ALSAQ-40 total score • Change from baseline to Week 24 in handgrip strength (average of both hands) Exploratory Endpoints • Time to first receipt, time to first use, time to daily use, time to dependence and number used of any of the following durable medical equipment items (manual wheelchair, power wheelchair, augmentative and alternative communication device, noninvasive ventilation (NIV) and/or gastrostomy tube) from randomization to the end of the 24-week doubleblind, placebo-controlled period or to the end of the study • Change from baseline to Week 24 in the four subdomain scores of the ALSFRS-R • Time spent in each MiToS stage and number of patients to transition stages from baseline to Week 24 • Change from baseline to Week 48 in ALSFRS-R total score • Change from baseline to Week 48 in forced vital capacity (FVC) • Combined assessment of change in ALSFRS-R total score, time to onset of respiratory insufficiency, and survival time up to Week 48 • Change from baseline to Week 24 in the megascore of muscle strength measured by hand-held dynamometry (HHD) in bilateral first dorsal interosseous muscles, abductor pollicus brevis muscles, and abductor digiti minimi muscles • Change from baseline to Week 24 and Week 48 in the EQ-5D-5L • Change from baseline to Week 24 and Week 48 in the EQ-Visual Analogue Scale (VAS);Timepoint(s) of evaluation of this end point: 24 weeks for secondary objectives 48 weeks for exploratory objectives | — |
Countries
Australia, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactVice President
Atlantic Research Group BV
Outcome results
None listed