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 (CENTAUR)

Study Purpose:

The CENTAUR trial will be 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.

Disease:

Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Active, currently recruiting

Phase:

Phase II

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

Study Director: Patrick Yeramian, MD, Amylyx Pharmaceuticals Inc.
Principal Investigator: Sabrina Paganoni, MD, Massachusetts General Hospital

Clinicaltrials.gov ID (11 digit #):

NCT03127514

Neals Affiliated?

Yes

Coordinating Center Contact Information

Carly Doyle / .(JavaScript must be enabled to view this email address) / 855-437-4823
.(JavaScript must be enabled to view this email address) 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:

Estimated Enrollment:

132

Estimated Study Start Date:

05/31/2017

Estimated Study Completion Date:

05/31/2019

Posting Last Modified Date:

06/19/2017

Date Study Added to alsconsortium.org:

05/02/2017

Eligibility Criteria

Gender:
Female, Male
Minimum Age:
18
Maximum Age:
80
Min Vital Capacity (% predicted normal):
60

Time since Symptom Onset:
<18
Time since Diagnosis:
N/A
Can participants use Riluzole?
Yes

Key Inclusion Criteria:
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

Key Exclusion Criteria:
Presence of tracheostomy
Exposure to PB, TUDCA 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 AST and/or 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 (SBP>160mmHg or 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.
Implantation of Diaphragm Pacing System (DPS)
Site Contact Information

ALS Center at the Swedish Neuroscience Institute
Seattle, Washington 98122
United States
Barrow Neurological Institute
Phoenix, Arizona 85013
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
Forbes Norris MDA/ALS Research Center - California Pacific Medical Center
San Francisco, California 94114
United States
Hennepin County Medical Center
Minneapolis, Minnesota 55415
United States
Johns Hopkins Hospital
Baltimore, Maryland 21287
United States
Massachusetts General Hospital
Oluwanisola Odesina / .(JavaScript must be enabled to view this email address) / 617-726-5059
Boston, Massachusetts 02114
United States
Mount Sinai Beth Israel
New York, New York 10003
United States
Neurology Associates P.C.
Lincoln, Nebraska 68506
United States
Ochsner Neuroscience Institute
New Orleans, Louisiana 70121
United States
Oregon Health & Science University
Portland, Oregon 97239
United States
Temple University Hospital
Philadelphia, Pennsylvania 19140
United States
Texas Neurology, P.A.
Dallas, Texas 75214
United States
The Ohio State University Wexner Medical Center
Columbus, Ohio 43221
United States
The Penn Comprehensive ALS Center
Philadelphia, Pennsylvania 19107
United States
UC Irvine Medical Center
Orange, California 92868
United States
University of Florida Medical Center
Gainesville, Florida 32610
United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa 52242
United States
University of Kentucky Medical Center
Lexington, Kentucky 40536
United States
University of Massachusetts Memorial Medical Center
Diane McKenna-Yasek, RN, BSN / .(JavaScript must be enabled to view this email address) / 508-856-4697
Worcester, Massachusetts 01655
United States
University of Michigan Medical Center
Ann Arbor, Michigan 48109
United States
University of Texas Health Science Center at San Antonio
Pamela Kittrell, RN, MSN, CCRC / .(JavaScript must be enabled to view this email address) / 210-450-0524
San Antonio, Texas 78229
United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina 27157
United States
Washington University Medical Center
Saint Louis, Missouri 63110
United States