Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment

Phase 3

Active, not recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Other: Placebo; Drug: AMX0035

• Registration Number: NCT05021536
• Lead Sponsor: Amylyx Pharmaceuticals Inc.

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

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 and survival over 48 week. The trial will also assess the effects of AMX0035 on slow vital capacity, quality of life and plasma biomarkers of ALS.

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: 2021-08-20
• Study First Submitted QC: 2021-08-20
• Study First Posted: 2021-08-25
• Study Start: 2021-10-28
• Primary Completion: 2024-01-19
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-09
• Last Update Posted: 2024-08-14
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 664

Inclusion Criteria

• 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

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Exclusion Criteria

• 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)
• Currently or previously treated within the last 30 days or planned exposure to any prohibited medications listed in Section 6.8 of the protocol

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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
AMX0035	AMX0035	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

Primary Outcome Measures

Name	Time	Method
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change	48 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
Rate of Decline in Slow Vital Capacity (SVC)	48 weeks	Respiratory muscle function will be assessed according to slow vital capacity (SVC). SVC is measured in an upright position for at least three trials per assessment. SVC volumes will be standardized to the percentage of predicted normal value based on age, sex, and height.
Participant Quality of Life (QOL)	48 weeks	QOL will be measured using the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) patient-reported outcome (PRO)
Assess Long-Term Survival	3 years from LPI	Long-Term Survival will be obtained by monitoring of all-cause mortality
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.
Number of Participants With Adverse Events	48 weeks	Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion

Trial Locations

Locations (69)

Lewis Katz School of Medicine at Temple University; 🇺🇸 Philadelphia, Pennsylvania, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University School of Medicine Outpatient Center; 🇺🇸 Baltimore, Maryland, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Rutgers University; 🇺🇸 New Brunswick, New Jersey, United States

Hôpitaux Universitaires de Marseille Timone; 🇫🇷 Marseille, France

Columbia University; 🇺🇸 New York, New York, United States

CHU de Limoges - Hôpital Dupuytren; 🇫🇷 Limoges, France

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Massachusetts; 🇺🇸 Worcester, Massachusetts, United States

Somnos Clinical Research; 🇺🇸 Lincoln, Nebraska, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

University of California Irvine; 🇺🇸 Orange, California, United States

Augusta University Neuroscience Center; 🇺🇸 Augusta, Georgia, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Le Centre Hospitalier Régional Universitaire de Tours; 🇫🇷 Tours, France

Ulm University Medical Centre; 🇩🇪 Ulm, Germany

Texas Neurology; 🇺🇸 Dallas, Texas, United States

Centro Hospitalar Universitário Lisboa-Norte; 🇵🇹 Lisbon, Portugal

CHU Nice; 🇫🇷 Nice, France

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

University Hospitals Leuven; 🇧🇪 Leuven, Belgium

University Medical Center Rostock; 🇩🇪 Rostock, Germany

CHRU de Lille - Hôpital Roger Salengro; 🇫🇷 Lille, France

Hospital San Rafael; 🇪🇸 Madrid, Spain

Azienda Ospedaliero Universitaria Di Modena; 🇮🇹 Modena, Italy

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain

University of Plymouth; 🇬🇧 Plymouth, United Kingdom

Hospital Universitari de Bellvitge-IDIBELL; 🇪🇸 Barcelona, Spain

Biodonostia Health Research Institute; Hospital Universitario Donostia; 🇪🇸 San Sebastián, Spain

Salford Royal Hospital Barnes; 🇬🇧 Salford, United Kingdom

Sheffield Institute for Translational Neuroscience (SITraN); 🇬🇧 Sheffield, United Kingdom

Healey & AMG Center for ALS Research at Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Hennepin Healthcare Research Institute; 🇺🇸 Minneapolis, Minnesota, United States

Swedish Neuroscience Institute; 🇺🇸 Seattle, Washington, United States

California Pacific Medical Center Research Institute; 🇺🇸 San Francisco, California, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Karolinska Institutet; 🇸🇪 Stockholm, Sweden

Virginia Commonwealth University; 🇺🇸 Henrico, Virginia, United States

Umeå University Hospital; 🇸🇪 Umeå, Sweden

King's College London; 🇬🇧 London, United Kingdom

CHU de Montpellier; 🇫🇷 Montpellier, France

Hôpital de la Salpêtrière; 🇫🇷 Paris, France

Hannover Medical School; 🇩🇪 Hannover, Germany

Jena University Hospital; 🇩🇪 Jena, Germany

Medizinische Fakultät Mannheim der Universität Heidelberg; 🇩🇪 Mannheim, Germany

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

University of Colorado; 🇺🇸 Aurora, Colorado, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Centrum Medyczne Linden; 🇵🇱 Kraków, Poland

Università degli Studi di Bari Aldo Moro; 🇮🇹 Bari, Italy

Centro Clinico NEMO; 🇮🇹 Milan, Italy

Trinity College Dublin/Beaumont Hospital; 🇮🇪 Dublin, Ireland

Università degli Studi della Campania Luigi Vanvitelli; 🇮🇹 Napoli, Italy

University of Milan Medical School; 🇮🇹 Milan, Italy

University of Padua; 🇮🇹 Padova, Italy

University of Torino; 🇮🇹 Turin, Italy

City Clinic Warsaw; 🇵🇱 Warsaw, Poland

UCL Queen Square Institute of Neurology; 🇬🇧 London, United Kingdom

Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer Cellule Mutualisée de Recherche Clinique (CMRC); 🇫🇷 Bron, France

Uniklinikum Dresden; 🇩🇪 Dresden, Germany

Hopital Gabriel Montpied Service de Neurologie; 🇫🇷 Clermont-Ferrand, France

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Austin Neuromuscular Center; 🇺🇸 Austin, Texas, United States

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

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands