Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment

NCT05021536 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: A35-004
• Study Type: interventional
• Target: 664
• Locations: 12 countries
• Sites: 69

Brief Summary

The Phoenix Trial is a randomized double blind placebo controlled Phase III trial to evaluate the safety and efficacy of AMX0035 for treatment of ALS

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change

  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.

  48 weeks

Secondary Outcomes (5)

• Participant Quality of Life (QOL)

  48 weeks

• Assess Long-Term Survival

  3 years from LPI

• Rate of Decline in Slow Vital Capacity (SVC)

  48 weeks

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change

  24 weeks

• Number of Participants With Adverse Events

  48 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered by mouth or via feeding tube for 48 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating

Other: Placebo

AMX0035

EXPERIMENTAL

Placebo administered by mouth or via feeding tube for 48 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating

Drug: AMX0035

Interventions

Placebo OTHER

Matching Placebo Comparator

Placebo

AMX0035 DRUG

Proprietary formulation of taurursodiol and sodium phenylbutyrate

AMX0035

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, at least 18 years of age
• Diagnosis of ALS (definite or clinically probable)
• Time since onset of first symptom of ALS should be \<24 months prior to randomization;
• If the participant is to be treated with riluzole and/or edaravone during the course of the trial, then treatment with riluzole and/or edaravone was, at the time of the screening visit, started and maintained at a stable regimen for at least 14 days for riluzole and/or for a full treatment cycle for edaravone;
• Capable of providing informed consent
• Capable and willing to follow trial procedures including visits to the trial clinic and visit requirements;
• 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

You may not qualify if:

• Presence of tracheostomy or permanent assisted ventilation(PAV)
• Slow Vital Capacity (SVC) less than 55%
• History of known allergy to phenyl butyrate or bile salts
• Abnormal liver function defined as bilirubin levels and/or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 5 times the upper limit of the normal (obtained within 12 weeks from first dose)
• Renal insufficiency as defined by eGFR \<60 mL/min/1.73m\^2 (obtained within 12 weeks from first dose)
• Pregnant women (confirmed by a pregnancy test within 7 days of first dose) or women currently breastfeeding
• Current severe biliary disease which may result in the Investigator medical judgement in biliary obstruction including for example active cholecystitis, primary biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gangrene of the gallbladder, abscess of the gallbladder
• History of Class III/IV heart failure (per New York Heart Association - NYHA)
• Participant under severe salt restriction where the added salt intake due to treatment would put the participant at risk, in the Investigator clinical judgment
• Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent, according to Investigator judgment
• Clinically significant unstable medical condition (other than ALS) (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, severe laboratory test anomaly or clinically significant electrocardiogram \[ECG\] changes) that would pose a risk to the participant if he/she were to participate in the trial, according to Investigator judgment
• Previous treatment for ALS with cellular therapies or gene therapies
• Currently enrolled in another trial involving use of an investigational therapy
• Previous treatment with PB or taurursodiol within 30 days from Screening
• Implantation of Diaphragm Pacing System (DPS)

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead

Study Sites (69)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

California Pacific Medical Center Research Institute

San Francisco, California, 94109, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32068, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Augusta University Neuroscience Center

Augusta, Georgia, 30912, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University School of Medicine Outpatient Center

Baltimore, Maryland, 21287, United States

Location

Healey & AMG Center for ALS Research at Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

Hennepin Healthcare Research Institute

Minneapolis, Minnesota, 55415, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Somnos Clinical Research

Lincoln, Nebraska, 68510, United States

Location

Rutgers University

New Brunswick, New Jersey, 08901, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27109, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Lewis Katz School of Medicine at Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78756, United States

Location

Texas Neurology

Dallas, Texas, 72506, United States

Location

Virginia Commonwealth University

Henrico, Virginia, 23233, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University Hospitals Leuven

Leuven, Belgium

Location

Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer Cellule Mutualisée de Recherche Clinique (CMRC)

Bron, France

Location

Hopital Gabriel Montpied Service de Neurologie

Clermont-Ferrand, France

Location

CHRU de Lille - Hôpital Roger Salengro

Lille, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, France

Location

Hôpitaux Universitaires de Marseille Timone

Marseille, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU Nice

Nice, France

Location

Hôpital de la Salpêtrière

Paris, France

Location

Le Centre Hospitalier Régional Universitaire de Tours

Tours, France

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Uniklinikum Dresden

Dresden, Germany

Location

Hannover Medical School

Hanover, Germany

Location

Jena University Hospital

Jena, Germany

Location

Medizinische Fakultät Mannheim der Universität Heidelberg

Mannheim, Germany

Location

University Medical Center Rostock

Rostock, Germany

Location

Ulm University Medical Centre

Ulm, Germany

Location

Trinity College Dublin/Beaumont Hospital

Dublin, Ireland

Location

Università degli Studi di Bari Aldo Moro

Bari, Italy

Location

Centro Clinico NEMO

Milan, Italy

Location

University of Milan Medical School

Milan, Italy

Location

Azienda Ospedaliero Universitaria Di Modena

Modena, Italy

Location

Università degli Studi della Campania Luigi Vanvitelli

Napoli, Italy

Location

University of Padua

Padua, Italy

Location

University of Torino

Turin, Italy

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Centrum Medyczne Linden

Krakow, Poland

Location

City Clinic Warsaw

Warsaw, Poland

Location

Centro Hospitalar Universitário Lisboa-Norte

Lisbon, Portugal

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitari de Bellvitge-IDIBELL

Barcelona, Spain

Location

Hospital San Rafael

Madrid, Spain

Location

Biodonostia Health Research Institute; Hospital Universitario Donostia

San Sebastián, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Karolinska Institutet

Stockholm, Sweden

Location

Umeå University Hospital

Umeå, Sweden

Location

King's College London

London, United Kingdom

Location

UCL Queen Square Institute of Neurology

London, United Kingdom

Location

University of Plymouth

Plymouth, United Kingdom

Location

Salford Royal Hospital Barnes

Salford, United Kingdom

Location

Sheffield Institute for Translational Neuroscience (SITraN)

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

sodium phenylbutyrate and taurursodiol

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Amylyx Study Director

  Amylyx Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 25, 2021
• Study Start: October 28, 2021
• Primary Completion: January 19, 2024
• Study Completion: January 1, 2026
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

DE (7); BE (1); IE (1); IT (7); US (28); PL (2); SE (2); GB (5); ES (5); PT (1); FR (9); NL (1)