Open Label Extension Study of AMX0035 in Patients With ALS
- Registration Number
- NCT03488524
- Lead Sponsor
- Amylyx Pharmaceuticals Inc.
- Brief Summary
This extension study, in which all participants received active treatment (AMX0035), was designed to assess the longer-term safety and therapeutic potential of AMX0035 for participants who have completed the Main Study (AMX3500, also known as CENTAUR).
- Detailed Description
The Centaur Open Label Extension Study (CENTAUR-OLE) is an extension study for patients with ALS who participated in the CENTAUR study (Study AMX3500). During the OLE, all participants received active treatment (AMX0035), and the investigators, evaluators, and participants remained blinded to the randomized treatment assigned at the beginning of the double-blind main study. The study was designed to assess the longer term safety and therapeutic potential of AMX0035.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- Completion of all visits in the randomized, double blind AMX3500 study. Participants who received tracheostomy or permanent assisted ventilation (PAV) during the course of the main study could enroll in the OLE if they completed all visits in the main study.
- Must enroll in the OLE within 28 days of the Week 24 visit of the main study.
- Signed informed consent to enter the OLE phase.
- Discontinued study drug prematurely in the double-blind phase of the study for reasons other than tracheostomy or PAV.
- Exposure to or anticipated requirement for any disallowed medication listed in the protocol.
- Any ongoing adverse events that in the opinion of the Site Investigator are clear contraindications to the study drug.
- Unstable cardiac or other life-threatening disease emergent during the randomized, double blind study
- Any major medical condition that in the opinion of the Site Investigator would interfere with the study and place the subject at increased risk.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AMX0035 AMX0035 AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g)
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From the Baseline Visit in the OLE study through Week 132 or the Early Discontinuation (Final Safety) Visit for each participant (for up to approximately 132 weeks) Number of participants with TEAEs from baseline in the OLE study through the last participant's last visit in the OLE
- Secondary Outcome Measures
Name Time Method Amyotrophic Lateral Sclerosis Rating Scale Revised Total Score (ALSFRS-R) Change in Slope From baseline in the Main Study through Week 24 of the OLE (48 weeks overall) Comparison of the difference in change in slope of Amyotrophic Lateral Sclerosis Rating Scale Revised (ALSFRS-R) total score from the Main Study baseline through Week 48 of the open-label extension (OLE) between the 2 treatment groups: those randomized to AMX0035 in the Main Study and those randomized to Placebo in the main study (all participants in the OLE received AMX0035). The slope is measured as a change in score divided by a change in time. ALSFRS-R consists of 12 items across 4 subdomains of function (bulbar, fine motor, gross motor, and breathing) with each item scored on a scale from 0 (total loss of function) to 4 (no loss of function). Total scores range from 0 to 48, with higher scores indicating better function.
Survival - Time to Death From date of first dose in the Main Study (each participant's Baseline Visit) through up to approximately 42 months (approximately 182 weeks) Median survival in months
Composite of Time to Hospitalization, Death or Death Equivalent From date of first dose in the Main Study (each participant's Baseline Visit) through up to approximately 42 months (approximately 182 weeks) The composite endpoint of time to hospitalization, death or death equivalent was defined as hospitalization, death, tracheostomy or PAV. PAV is defined as more than 22 hours daily of non-invasive mechanical ventilation for more than 1 week (7 days).
Slow Vital Capacity Change in Slope From baseline in the Main Study through Week 24 of the OLE (48 weeks overall) Comparison of the difference in change in slope of Slow Vital Capacity (SVC) from the Main Study baseline through Week 48 of the open-label extension (OLE) between the 2 treatment groups: those randomized to AMX0035 in the Main Study and those randomized to Placebo in the main study (all participants in the OLE received AMX0035). SVC volumes were standardized to predicted percent normalized values for respiratory muscle function based on age, sex, and height.
Accurate Testing of Limb Isometric Strength (ATLIS) Change in Slope - Upper Extremities From baseline in the Main Study through Week 24 of the OLE (48 weeks overall) Comparison of the difference in change in slope of Accurate Testing of Limb Isometric Strength (ATLIS) upper extremity score from the Main Study baseline through Week 48 of the open-label extension (OLE) between the 2 treatment groups: those randomized to AMX0035 in the Main Study and those randomized to Placebo in the main study (all participants in the OLE received AMX0035). The ATLIS device measures isometric strength in 6 upper extremity muscle groups. Raw values were standardized to percent predicted normal values for strength based on sex, age, weight, and height.
Accurate Testing of Limb Isometric Strength (ATLIS) Change in Slope - Lower Extremities From baseline in the Main Study through Week 24 of the OLE (48 weeks overall) Comparison of the difference in change in slope of Accurate Testing of Limb Isometric Strength (ATLIS) lower extremity score from the Main Study baseline through Week 48 of the open-label extension (OLE) between the 2 treatment groups: those randomized to AMX0035 in the Main Study and those randomized to Placebo in the main study (all participants in the OLE received AMX0035). The ATLIS device measures isometric strength in 6 lower extremity muscle groups. Raw values were standardized to percent predicted normal values for strength based on sex, age, weight, and height.
Accurate Testing of Limb Isometric Strength (ATLIS) Total Score Change in Slope From Baseline in the Main Study through Week 24 in the OLE (48 weeks overall) Comparison of the difference in change in slope of Accurate Testing of Limb Isometric Strength (ATLIS) total score from the Main Study baseline through Week 48 of the open-label extension (OLE) between the 2 treatment groups: those randomized to AMX0035 in the Main Study and those randomized to Placebo in the main study (all participants in the OLE received AMX0035). The ATLIS device measures isometric strength in 6 upper and 6 lower extremity muscle groups. Raw values were standardized to percent predicted normal values for strength based on sex, age, weight, and height.
Trial Locations
- Locations (24)
Barrow Neurological Institute-Dignity Health, St Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
University of California, Irvine
🇺🇸Orange, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
University of South Florida College of Medicine
🇺🇸Tampa, Florida, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
University of Iowa, Carver College of Medicine
🇺🇸Iowa City, Iowa, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Ochsner Neuroscience Institute
🇺🇸New Orleans, Louisiana, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Scroll for more (14 remaining)Barrow Neurological Institute-Dignity Health, St Joseph's Hospital and Medical Center🇺🇸Phoenix, Arizona, United States