Open Label Extension Study of AMX0035 in Patients With ALS

Amylyx Pharmaceuticals Inc.90 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Amyotrophic Lateral Sclerosis ALS

Interventions

AMX0035DRUG

Combination therapy of PB and TURSO

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. Must enroll in the OLE within 28 days of the Week 24 visit of the main study. 3. Signed informed consent to enter the OLE phase. Exclusion Criteria: 1. Discontinued study drug prematurely in the double-blind phase of the study for reasons other than tracheostomy or PAV. 2. Exposure to or anticipated requirement for any disallowed medication listed in the protocol. 3. Any ongoing adverse events that in the opinion of the Site Investigator are clear contraindications to the study drug. 4. Unstable cardiac or other life-threatening disease emergent during the randomized, double blind study 5. Any major medical condition that in the opinion of the Site Investigator would interfere with the study and place the subject at increased risk.

Locations (24)

Outcomes

Primary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Number of participants with TEAEs from baseline in the OLE study through the last participant's last visit in the OLE

Time frame: 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)

Secondary Outcomes

Amyotrophic Lateral Sclerosis Rating Scale Revised Total Score (ALSFRS-R) Change in Slope

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.

Time frame: From baseline in the Main Study through Week 24 of the OLE (48 weeks overall)

Survival - Time to Death

Median survival in months

Time frame: From date of first dose in the Main Study (each participant's Baseline Visit) through up to approximately 42 months (approximately 182 weeks)

Composite of Time to Hospitalization, Death or Death Equivalent

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).

Time frame: From date of first dose in the Main Study (each participant's Baseline Visit) through up to approximately 42 months (approximately 182 weeks)

Data from ClinicalTrials.gov

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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

...and 14 more locations

Accurate Testing of Limb Isometric Strength (ATLIS) Change in Slope - Upper Extremities

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.

Time frame: From baseline in the Main Study through Week 24 of the OLE (48 weeks overall)

Accurate Testing of Limb Isometric Strength (ATLIS) Change in Slope - Lower Extremities

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.

Time frame: From baseline in the Main Study through Week 24 of the OLE (48 weeks overall)

Slow Vital Capacity Change in Slope

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.

Time frame: From baseline in the Main Study through Week 24 of the OLE (48 weeks overall)

Accurate Testing of Limb Isometric Strength (ATLIS) Total Score Change in Slope

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.

Time frame: From Baseline in the Main Study through Week 24 in the OLE (48 weeks overall)