Open Label Extension Study of AMX0035 in Patients With ALS (CENTAUR-OLE)

Evaluation of the Safety, Tolerability, Efficacy, and Activity of AMX0035, a Fixed Combination of Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), for Treatment of Amyotrophic Lateral Sclerosis: Open-Label Extension

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).

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis; ALS
• Intervention / Treatment: Drug: AMX0035

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute-Dignity Health, St Joseph's Hospital and Medical Center
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine
    • San Francisco, California, United States, 94114
      • California Pacific Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Tampa, Florida, United States, 33612
      • University of South Florida College of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, Carver College of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Neuroscience Institute
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan, Michigan Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Neurology Associates, PC
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43221
      • The Ohio State University, Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • The Penn Comprehensive Neuroscience Center
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology, PA
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center, San Antonio
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMX0035; AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g)	Drug: AMX0035; Combination therapy of PB and TURSO; Other Names: Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO, also known as Ursodoxicoltaurine or Tauroursodeoxycholic Acid [TUDCA])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline in the Main Study through Week 24 of the OLE (48 weeks overall)
Survival - Time to Death	Median survival in months	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).	From date of first dose in the Main Study (each participant's Baseline Visit) through up to approximately 42 months (approximately 182 weeks)
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.	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.	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.	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.	From Baseline in the Main Study through Week 24 in the OLE (48 weeks overall)

Collaborators and Investigators

• Sponsor: Amylyx Pharmaceuticals Inc.
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Sabrina Paganoni, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Paganoni S, Watkins C, Cawson M, Hendrix S, Dickson SP, Knowlton N, Timmons J, Manuel M, Cudkowicz M. Survival analyses from the CENTAUR trial in amyotrophic lateral sclerosis: Evaluating the impact of treatment crossover on outcomes. Muscle Nerve. 2022 Aug;66(2):136-141. doi: 10.1002/mus.27569. Epub 2022 May 31.
• Paganoni S, Hendrix S, Dickson SP, Knowlton N, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson TD, Jackson C, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha SS, Miller TM, Scelsa SN, Vu TH, Fournier C, Johnson KM, Swenson A, Goyal N, Pattee GL, Babu S, Chase M, Dagostino D, Hall M, Kittle G, Eydinov M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Yu H, Cohen J, Klee J, Tanzi R, Gilbert W, Yeramian P, Cudkowicz M. Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. J Neurol Neurosurg Psychiatry. 2022 May 16;93(8):871-5. doi: 10.1136/jnnp-2022-329024. Online ahead of print.
• Paganoni S, Hendrix S, Dickson SP, Knowlton N, Macklin EA, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson TD, Jackson CE, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha S, Miller TM, Scelsa SN, Vu TH, Fournier CN, Glass JD, Johnson KM, Swenson A, Goyal NA, Pattee GL, Andres PL, Babu S, Chase M, Dagostino D, Hall M, Kittle G, Eydinov M, McGovern M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, St Pierre ME, Tustison E, Vigneswaran P, Walker J, Yu H, Chan J, Wittes J, Yu ZF, Cohen J, Klee J, Leslie K, Tanzi RE, Gilbert W, Yeramian PD, Schoenfeld D, Cudkowicz ME. Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Muscle Nerve. 2021 Jan;63(1):31-39. doi: 10.1002/mus.27091. Epub 2020 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 5, 2018

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: July 24, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Anti-Infective Agents; Antineoplastic Agents; Gastrointestinal Agents; Antiviral Agents; Cholagogues and Choleretics; 4-phenylbutyric acid; Ursodoxicoltaurine
• Other Study ID Numbers: AMX-3500-OLE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No