Evaluation of the Safety, Tolerability, Efficacy and Activity of AMX0035, a Fixed Combination of Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), for the Treatment of ALS

Study Purpose:

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.

Study Status:

Not recruiting


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

Study Type:


Type of Intervention:

Drug, N/A

Intervention Name:

AMX0035, Placebo




Phase 2

Study Chair(s)/Principal Investigator(s):

Patrick Yeramian, MD, Amylyx Pharmaceuticals Inc., Sabrina Paganoni, MD, Massachusetts General Hospital

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

Massachusetts General Hospital, NCRI

Boston, Massachusetts, 02114 United States

Full Study Summary:

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.

Study Sponsor:

Amylyx Pharmaceuticals Inc.

Participant Duration:

6 months

Estimated Enrollment:


Estimated Study Start Date:

06 / 22 / 2017

Estimated Study Completion Date:

11 / 24 / 2019

Posting Last Modified Date:

08 / 11 / 2021

Date Study Added to neals.org:

04 / 25 / 2017

Minimum Age:

18 Years

Maximum Age:

80 Years

Can participants use Riluzole?


Key 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

Key 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)

Barrow Neurological Institute

Phoenix, Arizona 85013
United States

UC Irvine Medical Center

Orange, California 92868
United States

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

San Francisco, California 94114
United States

University of Florida Medical Center

Gainesville, Florida 32610
United States

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

Tampa, Florida 33612
United States

Emory University Hospital

Atlanta, Georgia 30322
United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa 52242
United States

University of Kentucky Medical Center

Lexington, Kentucky 40536
United States

Ochsner Neuroscience Institute

New Orleans, Louisiana 70121
United States

Johns Hopkins Hospital

Baltimore, Maryland 21287
United States

Massachusetts General Hospital

Boston, Massachusetts 02114
United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts 01655
United States

University of Michigan Medical Center

Ann Arbor, Michigan 48109
United States

Hennepin County Medical Center

Minneapolis, Minnesota 55415
United States

Washington University Medical Center

Saint Louis, Missouri 63110
United States

Neurology Associates P.C.

Lincoln, Nebraska 68506
United States

Mount Sinai Beth Israel

New York, New York 10003
United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina 27157
United States

The Ohio State University Wexner Medical Center

Columbus, Ohio 43221
United States

Oregon Health & Science University

Portland, Oregon 97239
United States

The Penn Comprehensive ALS Center

Philadelphia, Pennsylvania 19107
United States

Temple University Hospital

Philadelphia, Pennsylvania 19140
United States

Texas Neurology, P.A.

Dallas, Texas 75214
United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229
United States

ALS Center at the Swedish Neuroscience Institute

Seattle, Washington 98122
United States