Open Label Extension Study of AMX0035 in Patients With ALS

NCT03488524 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AMX-3500-OLE
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 24

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).

Conditions

Amyotrophic Lateral Sclerosis; ALS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (1)

AMX0035

EXPERIMENTAL

AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g)

Drug: AMX0035

Interventions

AMX0035 DRUG

Combination therapy of PB and TURSO

Also known as: Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO, also known as Ursodoxicoltaurine or Tauroursodeoxycholic Acid [TUDCA])

AMX0035

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead
• Massachusetts General Hospital: collaborator

Study Sites (24)

Barrow Neurological Institute-Dignity Health, St Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

University of California, Irvine

Orange, California, 92868, United States

Location

California Pacific Medical Center

San Francisco, California, 94114, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

University of South Florida College of Medicine

Tampa, Florida, 33612, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

University of Iowa, Carver College of Medicine

Iowa City, Iowa, 52242, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Ochsner Neuroscience Institute

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan, Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

Neurology Associates, PC

Lincoln, Nebraska, 68506, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University, Wexner Medical Center

Columbus, Ohio, 43221, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The Penn Comprehensive Neuroscience Center

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Texas Neurology, PA

Dallas, Texas, 75214, United States

Location

University of Texas Health Science Center, San Antonio

San Antonio, Texas, 78229, United States

Location

Swedish Neuroscience Center

Seattle, Washington, 98122, United States

Location

Related Publications (3)

• 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.

  PMID: 35508892 RESULT

• 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.

  PMID: 35577511 RESULT

• 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.

  PMID: 33063909 RESULT

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

sodium phenylbutyrate and taurursodiol; 4-phenylbutyric acid; ursodoxicoltaurine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Amylyx Pharmaceuticals, Inc.

medinfo@amylyx.com

(877) 374-1208

Study Officials

• Sabrina Paganoni, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label extension study to CENTAUR (AMX3500)

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: April 5, 2018
• Study Start: March 29, 2018
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: August 13, 2025
• Results First Posted: August 13, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)