AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT03127514

Last Updated: 2024-05-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

137 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-22

Study Completion Date

2019-11-24

Brief Summary

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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.

Detailed Description

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AMX0035 is a combination therapy designed to reduce neuronal death through blockade of key cellular death pathways originating in the mitochondria and endoplasmic reticulum (ER). This clinical trial is designed to demonstrate that treatment is safe, tolerable, and able to slow decline in function as measured by the ALSFRS-R. The trial will also assess the effects of AMX0035 on muscle strength, vital capacity, and biomarkers of ALS including markers of neuronal death and neuroinflammation.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching Placebo Comparator

AMX0035

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

Group Type EXPERIMENTAL

AMX0035

Intervention Type DRUG

AMX0035

Interventions

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AMX0035

AMX0035

Intervention Type DRUG

Placebo

Matching Placebo Comparator

Intervention Type OTHER

Other Intervention Names

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Proprietary formulation of taurursodiol and sodium phenylbutyrate

Eligibility Criteria

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Inclusion Criteria

1. Male or female, aged 18-80 years of age
2. Sporadic or familial ALS diagnosed as definite as defined by the World Federation of Neurology revised El Escorial criteria
3. Less than or equal to 18 months since ALS symptom onset
4. Capable of providing informed consent and following trial procedures
5. Slow Vital Capacity (SVC) \>60% of predicted value for gender, height, and age at the Screening Visit
6. 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.
7. 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
8. 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

Exclusion Criteria

1. Presence of tracheostomy
2. 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
3. History of known allergy to PB or bile salts
4. Abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of the normal
5. Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal
6. Poorly controlled arterial hypertension (systolic blood pressure (SBP)\>160mmHg or diastolic blood pressure (DBP)\>100mmHg) at the Screening Visit
7. Pregnant women or women currently breastfeeding
8. History of cholecystectomy
9. 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.
10. History of Class III/IV heart failure (per New York Heart Association - NYHA)
11. Severe pancreatic or intestinal disorders that may alter the enterohepatic circulation and absorption of TUDCA including biliary infections, pancreatitis and ileal resection
12. 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
13. Clinically significant unstable medical condition (other than ALS) that would pose a risk to the subject if they were to participate in the study
14. Active participation in an ALS clinical trial evaluating a small molecule within 30 days of the Screening Visit
15. 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.
16. Implantation of Diaphragm Pacing System (DPS)
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ALS Finding a Cure

OTHER

Sponsor Role collaborator

ALS Association

OTHER

Sponsor Role collaborator

Northeast ALS Consortium

OTHER

Sponsor Role collaborator

Neurological Clinical Research Institute at Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Leandro P. Rizzuto Foundation

OTHER

Sponsor Role collaborator

Amylyx Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick Yeramian, MD

Role: STUDY_DIRECTOR

Amylyx Pharmaceuticals Inc.

Sabrina Paganoni, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

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

San Francisco, California, United States

Site Status

University of Florida Medical Center

Gainesville, Florida, United States

Site Status

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

Tampa, Florida, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kentucky Medical Center

Lexington, Kentucky, United States

Site Status

Ochsner Neuroscience Institute

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Washington University Medical Center

St Louis, Missouri, United States

Site Status

Neurology Associates P.C.

Lincoln, Nebraska, United States

Site Status

Mount Sinai Beth Israel

New York, New York, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

The Penn Comprehensive ALS Center

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Texas Neurology, P.A.

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

ALS Center at the Swedish Neuroscience Institute

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 25664595 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18688762 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38050066 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35577511 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32877582 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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AMX-3500

Identifier Type: -

Identifier Source: org_study_id

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