AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

NCT03127514 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AMX-3500
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 25

Brief Summary

The CENTAUR trial was a 2:1 (active:placebo) randomized, double-blind, placebo-controlled Phase II trial to evaluate the safety and efficacy of AMX0035 for the treatment of ALS.

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Nervous System Diseases; Central Nervous System Diseases

Keywords

Randomized; Double-blind; Placebo-controlled; Amyotrophic Lateral Sclerosis; Sodium Phenylbutyrate; Tauroursodeoxycholic Acid

Outcome Measures

Primary Outcomes (3)

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change

  Change in slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over treatment duration. The 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.

  24 Weeks

• Number of Participants With Adverse Events

  Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion

  24 Weeks

• Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation

  A comparison of the number of participants in each group able to remain on study drug until planned discontinuation between groups

  24 weeks

Secondary Outcomes (4)

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

  24 Weeks

• Change in Plasma Levels of Phosphorylated Axonal Neurofilament H Subunit (pNF-H)

  24 Weeks

• Rate of Decline in Slow Vital Capacity (SVC)

  24 Weeks

• Death, Tracheostomy, and Hospitalization

  24 Weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating

Other: Placebo

AMX0035

EXPERIMENTAL

AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating

Drug: AMX0035

Interventions

AMX0035 DRUG

AMX0035

Also known as: Proprietary formulation of taurursodiol and sodium phenylbutyrate

AMX0035

Placebo OTHER

Matching Placebo Comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 18-80 years of age
• Sporadic or familial ALS diagnosed as definite as defined by the World Federation of Neurology revised El Escorial criteria
• Less than or equal to 18 months since ALS symptom onset
• Capable of providing informed consent and following trial procedures
• Slow Vital Capacity (SVC) \>60% of predicted value for gender, height, and age at the Screening Visit
• Subjects must either not take riluzole or be on a stable dose of riluzole for at least 30 days prior to the Screening Visit. Riluzole-naïve subjects are permitted in the study.
• Women of child bearing potential (e.g. not post-menopausal for at least one year or surgically sterile) must agree to use adequate birth control for the duration of the study and 3 months after last dose of study drug. Women must not be planning to become pregnant for the duration of the study and 3 months after last dose of study drug
• Men must agree to practice contraception for the duration of the study and 3 months after last dose of study drug. Men must not plan to father a child or provide for sperm donation for the duration of the study and 3 months after last dose of study drug

You may not qualify if:

• Presence of tracheostomy
• Exposure to PB, Taurursodiol or UDCA within 3 months prior to the Screening Visit or planning to use these medications during the course of the study
• History of known allergy to PB or bile salts
• Abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of the normal
• Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal
• Poorly controlled arterial hypertension (systolic blood pressure (SBP)\>160mmHg or diastolic blood pressure (DBP)\>100mmHg) at the Screening Visit
• Pregnant women or women currently breastfeeding
• History of cholecystectomy
• Biliary disease which impedes biliary flow including active cholecystitis, primary biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gallbladder polyps, gangrene of the gallbladder, abscess of the gallbladder.
• History of Class III/IV heart failure (per New York Heart Association - NYHA)
• Severe pancreatic or intestinal disorders that may alter the enterohepatic circulation and absorption of TUDCA including biliary infections, pancreatitis and ileal resection
• The presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the subject to provide informed consent, according to Site Investigator judgment
• Clinically significant unstable medical condition (other than ALS) that would pose a risk to the subject if they were to participate in the study
• Active participation in an ALS clinical trial evaluating a small molecule within 30 days of the Screening Visit
• Exposure at any time to any biologic under investigation for the treatment of subjects with ALS (off-label use or investigational) including cell therapies, gene therapies, and monoclonal antibodies.

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead
• ALS Finding a Cure: collaborator
• ALS Association: collaborator
• Northeast ALS Consortium: collaborator
• Neurological Clinical Research Institute at Massachusetts General Hospital: collaborator
• Leandro P. Rizzuto Foundation: collaborator

Study Sites (25)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Forbes Norris MDA/ALS Research Center - California Pacific Medical Center

San Francisco, California, 94114, United States

Location

University of Florida Medical Center

Gainesville, Florida, 32610, United States

Location

Carol and Frank Morsini Center for Advanced Health Care - University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics

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, 21287, 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 Medical Center

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 P.C.

Lincoln, Nebraska, 68506, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Wake Forest Baptist Medical Center

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 ALS Center

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Texas Neurology, P.A.

Dallas, Texas, 75214, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

ALS Center at the Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

Related Publications (5)

• Elia AE, Lalli S, Monsurro MR, Sagnelli A, Taiello AC, Reggiori B, La Bella V, Tedeschi G, Albanese A. Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis. Eur J Neurol. 2016 Jan;23(1):45-52. doi: 10.1111/ene.12664. Epub 2015 Feb 9.

  PMID: 25664595 BACKGROUND

• Cudkowicz ME, Andres PL, Macdonald SA, Bedlack RS, Choudry R, Brown RH Jr, Zhang H, Schoenfeld DA, Shefner J, Matson S, Matson WR, Ferrante RJ; Northeast ALS and National VA ALS Research Consortiums. Phase 2 study of sodium phenylbutyrate in ALS. Amyotroph Lateral Scler. 2009 Apr;10(2):99-106. doi: 10.1080/17482960802320487.

  PMID: 18688762 BACKGROUND

• Bowser R, An J, Mehta L, Chen J, Timmons J, Cudkowicz M, Paganoni S. Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial. J Neurol Neurosurg Psychiatry. 2024 Jun 17;95(7):605-608. doi: 10.1136/jnnp-2023-332106.

  PMID: 38050066 DERIVED

• 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 DERIVED

• Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson T, 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, Dickson SP, Ellison N, Hall M, Hendrix K, Kittle G, McGovern M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Walker J, Yu H, Chan J, Wittes J, Cohen J, Klee J, Leslie K, Tanzi RE, Gilbert W, Yeramian PD, Schoenfeld D, Cudkowicz ME. Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020 Sep 3;383(10):919-930. doi: 10.1056/NEJMoa1916945.

  PMID: 32877582 DERIVED

Related Links

• TUDCA in patients with ALS

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Nervous System Diseases; Central Nervous System Diseases

Interventions

sodium phenylbutyrate and taurursodiol; 4-phenylbutyric acid

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Amylyx Pharmaceuticals, Head of Clinical R&D
• Organization: Amylyx Pharmaceuticals

medinfo@amylyx.com

(617) 682-0917

Study Officials

• Patrick Yeramian, MD

  Amylyx Pharmaceuticals Inc.

  STUDY DIRECTOR

• Sabrina Paganoni, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2017
• First Posted: April 25, 2017
• Study Start: June 22, 2017
• Primary Completion: September 25, 2019
• Study Completion: November 24, 2019
• Last Updated: May 16, 2024
• Results First Posted: August 11, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

US (25)