AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Phase 2

Completed

• Conditions: Amyotrophic Lateral Sclerosis; Spinal Cord Diseases; Nervous System Diseases; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Central Nervous System Diseases
• Interventions: Drug: AMX0035; Other: Placebo

• Registration Number: NCT03127514
• Lead Sponsor: 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2017-04-12
• Study First Submitted QC: 2017-04-20
• Study First Posted: 2017-04-25
• Study Start: 2017-06-22
• Primary Completion: 2019-09-25
• Study Completion: 2019-11-24
• Results First Submitted: 2021-05-16
• Results First Submitted QC: 2021-07-20
• Results First Posted: 2021-08-11
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 137

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AMX0035	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
Placebo	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	24 Weeks	Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion
Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation	24 weeks	A comparison of the number of participants in each group able to remain on study drug until planned discontinuation between groups
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change	24 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Death, Tracheostomy, and Hospitalization	24 Weeks	The composite outcome was defined as death, a death-equivalent event (which consisted of only tracheostomy in one participant in this trial), or hospitalization, whichever occurred first; there were no instances of permanent ventilation delivered by noninvasive means in the study.
Accurate Testing of Limb Isometric Strength (ATLIS) Total Score Change	24 Weeks	The ATLIS device assess the isometric muscle strength of six upper-limb and six lower-limb muscle groups. At least two trials are performed for each muscle group to assess change in rate of decline of isometric muscle strength over treatment duration. Values are standardized to the percentage of predicted normal strength based on sex, age, weight, and height. Results are presented as percent of predicted normal.
Rate of Decline in Slow Vital Capacity (SVC)	24 Weeks	Respiratory muscle function was assessed according to slow vital capacity (SVC). SVC was measured in an upright position for at least three trials per assessment. SVC volumes were standardized to the percentage of predicted normal value based on age, sex, and height.
Change in Plasma Levels of Phosphorylated Axonal Neurofilament H Subunit (pNF-H)	24 Weeks	Neuronal degeneration releases phosphorylated axonal neurofilament H subunit (pNF-H) into the cerebrospinal fluid and subsequently the blood and is thought to be a potential biomarker of motor neuron degeneration; elevated plasma levels of pNF-H are presumed to correlate with neuronal injury. Change in levels of plasma pNF-H were measured from baseline to week 24

Trial Locations

Locations (25)

Temple University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Texas Neurology, P.A.; 🇺🇸 Dallas, Texas, United States

The Penn Comprehensive ALS Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

The Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

ALS Center at the Swedish Neuroscience Institute; 🇺🇸 Seattle, Washington, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

UC Irvine Medical Center; 🇺🇸 Orange, California, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Massachusetts Memorial Medical Center; 🇺🇸 Worcester, Massachusetts, United States

Washington University Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Neurology Associates P.C.; 🇺🇸 Lincoln, Nebraska, United States

Mount Sinai Beth Israel; 🇺🇸 New York, New York, United States

Forbes Norris MDA/ALS Research Center - California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

Carol and Frank Morsini Center for Advanced Health Care - University of South Florida; 🇺🇸 Tampa, Florida, United States

University of Michigan Medical Center; 🇺🇸 Ann Arbor, Michigan, United States

Wake Forest Baptist Medical Center; 🇺🇸 Winston-Salem, North Carolina, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

University of Florida Medical Center; 🇺🇸 Gainesville, Florida, United States

Ochsner Neuroscience Institute; 🇺🇸 New Orleans, Louisiana, United States

University of Kentucky Medical Center; 🇺🇸 Lexington, Kentucky, United States