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

Massachusetts General Hospital, NCRI
Emily Engel, B.S. / .(JavaScript must be enabled to view this email address) / 617-724-7210
.(JavaScript must be enabled to view this email address) 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:

24 weeks

Estimated Enrollment:

132

Estimated Study Start Date:

05/31/2017

Estimated Study Completion Date:

05/31/2019

Posting Last Modified Date:

12/05/2017

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 months

    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

    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
    Jennifer Steshyn / .(JavaScript must be enabled to view this email address) / 352-273-9022
    Gainesville, Florida 32610
    United States

    Carol and Frank Morsini Center for Advanced Health Care - University of South Florida
    Brittany Harvey / .(JavaScript must be enabled to view this email address) / 813-974-9413
    Tampa, Florida 33612
    United States

    Emory University
    Janet Brantley / .(JavaScript must be enabled to view this email address) / 404-727-1673
    Atlanta, Georgia 30322
    United States

    University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242
    United States

    University of Kentucky Medical Center
    Meha Joshi / .(JavaScript must be enabled to view this email address) / 859-218-5046
    Lexington, Kentucky 40536
    United States

    Ochsner Neuroscience Institute
    Ashley Laroche / .(JavaScript must be enabled to view this email address) / 504-703-0755
    New Orleans, Louisiana 70121
    United States

    Johns Hopkins Hospital
    Kristen Riley / .(JavaScript must be enabled to view this email address) / 410-955-9036
    Baltimore, Maryland 21287
    United States

    Massachusetts General Hospital
    Aileen Shaughnessy / .(JavaScript must be enabled to view this email address) / 617-643-0801
    Boston, Massachusetts 02114
    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

    Hennepin County Medical Center
    Cindy Rohde / .(JavaScript must be enabled to view this email address) / 612-873-2607
    Twin Cities
    Minneapolis, Minnesota 55415
    United States

    Washington University Medical Center
    Jennifer Jockel-Balsarotti / .(JavaScript must be enabled to view this email address) / 314-362-8624
    Saint Louis, Missouri 63110
    United States

    Neurology Associates P.C.
    Lincoln, Nebraska 68506
    United States

    Mount Sinai Beth Israel
    Emily Ripps / .(JavaScript must be enabled to view this email address) / 212-844-6188
    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
    Louisa Mezache / .(JavaScript must be enabled to view this email address) / 614-685-3030
    Columbus, Ohio 43221
    United States

    Oregon Health & Science University
    Diana Dimitrova / .(JavaScript must be enabled to view this email address) / 503-494-7269
    Portland, Oregon 97239
    United States

    The Penn Comprehensive ALS Center
    Kelly Almasy / .(JavaScript must be enabled to view this email address) / 215-829-5041
    Philadelphia, Pennsylvania 19107
    United States

    Temple University Hospital
    Philadelphia, Pennsylvania 19140
    United States

    Texas Neurology, P.A.
    Todd Morgan / .(JavaScript must be enabled to view this email address) / 214-827-3610, ext. 228
    Dallas, Texas 75214
    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

    ALS Center at the Swedish Neuroscience Institute
    Lindsey Maassel / .(JavaScript must be enabled to view this email address) / 206-320-7121
    Seattle, Washington 98122
    United States