AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

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

Sponsors

Lead Sponsor: Amylyx Pharmaceuticals Inc.

Collaborator: ALS Finding a Cure
ALS Association
Northeast ALS Consortium
Neurological Clinical Research Institute at Massachusetts General Hospital
Leandro P. Rizzuto Foundation

Source Amylyx Pharmaceuticals Inc.
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.

Detailed Description

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.

Overall Status Completed
Start Date 2017-06-22
Completion Date 2019-11-24
Primary Completion Date 2019-09-25
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change 24 Weeks
Number of Participants With Adverse Events 24 Weeks
Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation 24 weeks
Secondary Outcome
Measure Time Frame
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
Enrollment 137
Condition
Intervention

Intervention Type: Drug

Intervention Name: AMX0035

Description: AMX0035

Arm Group Label: AMX0035

Other Name: Proprietary formulation of taurursodiol and sodium phenylbutyrate

Intervention Type: Other

Intervention Name: Placebo

Description: Matching Placebo Comparator

Arm Group Label: Placebo

Eligibility

Criteria:

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)

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Overall Official
Location
Facility:
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
Location Countries

United States

Verification Date

2021-07-01

Responsible Party

Type: Sponsor

Keywords
Condition Browse
Number Of Arms 2
Arm Group

Label: Placebo

Type: Placebo Comparator

Description: 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

Label: AMX0035

Type: Experimental

Description: 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

Acronym CENTAUR
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News