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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05021536
Other study ID # A35-004
Secondary ID
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date October 28, 2021
Est. completion date March 1, 2024

Study information

Verified date January 2023
Source Amylyx Pharmaceuticals Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 600
Est. completion date March 1, 2024
Est. primary completion date November 1, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 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

Study Design


Intervention

Other:
Placebo
Matching Placebo Comparator
Drug:
AMX0035
Proprietary formulation of taurursodiol and sodium phenylbutyrate

Locations

Country Name City State
Belgium University Hospitals Leuven Leuven
France Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer Cellule Mutualisée de Recherche Clinique (CMRC) Bron
France Hopital Gabriel Montpied Service de Neurologie Clermont-Ferrand
France CHRU de Lille - Hôpital Roger Salengro Lille
France CHU de Limoges - Hôpital Dupuytren Limoges
France Hôpitaux Universitaires de Marseille Timone Marseille
France CHU de Montpellier Montpellier
France CHU Nice Nice
France Hôpital de la Salpêtrière Paris
France Le Centre Hospitalier Régional Universitaire de Tours Tours
Germany Charité - Universitätsmedizin Berlin Berlin
Germany Uniklinikum Dresden Dresden
Germany Hannover Medical School Hannover
Germany Jena University Hospital Jena
Germany Medizinische Fakultät Mannheim der Universität Heidelberg Mannheim
Germany University Medical Center Rostock Rostock
Germany Ulm University Medical Centre Ulm
Ireland Trinity College Dublin/Beaumont Hospital Dublin
Italy Università degli Studi di Bari Aldo Moro Bari
Italy Centro Clinico NEMO Milan
Italy University of Milan Medical School Milan
Italy Azienda Ospedaliero Universitaria Di Modena Modena
Italy Università degli Studi della Campania Luigi Vanvitelli Napoli
Italy University of Padua Padova
Italy University of Torino Turin
Netherlands University Medical Center Utrecht Utrecht
Poland Centrum Medyczne Linden Kraków
Poland City Clinic Warsaw Warsaw
Portugal Centro Hospitalar Universitário Lisboa-Norte Lisbon
Spain Hospital del Mar Barcelona
Spain Hospital Universitari de Bellvitge-IDIBELL Barcelona
Spain Hospital San Rafael Madrid
Spain Biodonostia Health Research Institute; Hospital Universitario Donostia San Sebastián
Spain Hospital Universitario y Politécnico La Fe Valencia
Sweden Karolinska Institutet Stockholm
Sweden Umeå University Hospital Umeå
United Kingdom King's College London London
United Kingdom UCL Queen Square Institute of Neurology London
United Kingdom University of Plymouth Plymouth
United Kingdom Salford Royal Hospital Barnes Salford
United Kingdom Sheffield Institute for Translational Neuroscience (SITraN) Sheffield
United States Emory University Atlanta Georgia
United States Augusta University Neuroscience Center Augusta Georgia
United States University of Colorado Aurora Colorado
United States Austin Neuromuscular Center Austin Texas
United States Johns Hopkins University School of Medicine Outpatient Center Baltimore Maryland
United States Healey & AMG Center for ALS Research at Massachusetts General Hospital Boston Massachusetts
United States University of North Carolina at Chapel Hill Chapel Hill North Carolina
United States Northwestern University Chicago Illinois
United States The Ohio State University Columbus Ohio
United States Texas Neurology Dallas Texas
United States University of Florida Gainesville Florida
United States Virginia Commonwealth University Henrico Virginia
United States Somnos Clinical Research Lincoln Nebraska
United States University of Southern California Los Angeles California
United States Hennepin Healthcare Research Institute Minneapolis Minnesota
United States Rutgers University New Brunswick New Jersey
United States Columbia University New York New York
United States University of California Irvine Orange California
United States Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania
United States University of Pennsylvania Philadelphia Pennsylvania
United States Barrow Neurological Institute Phoenix Arizona
United States Washington University School of Medicine Saint Louis Missouri
United States California Pacific Medical Center Research Institute San Francisco California
United States Swedish Neuroscience Institute Seattle Washington
United States University of Washington Seattle Washington
United States University of South Florida Tampa Florida
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States University of Massachusetts Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Amylyx Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Ireland,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change And Survival 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
Primary Number of Participants With Adverse Events Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion 48 weeks
Primary Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation A comparison o0f the number of participants in each group able to remain on study drug until planned discontinuation between groups 48 weeks
Secondary Rate of Decline in Slow Vital Capacity (SVC) 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. 48 weeks
Secondary Participant Quality of Life (QOL) QOL will be measured using the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) patient-reported outcome (PRO) 48 weeks
Secondary Decline in King's and MiToS Stages The decline in King's and MiToS (Milano-Torino staging) will be derived from ALSFRS-R data 48 weeks
Secondary Ventilation Free Survival The composite outcome is defined as death, a death-equivalent event (tracheostomy), or hospitalization, whichever occurs first 48 weeks
Secondary Participant Health Status Participant health status will be measured using the EQ-5D descriptive system and the EQ visual analogue scale [EQ VAS] patient reported outcomes questionnaire 48 weeks
Secondary Assess Long-Term Survival Long-Term Survival will be obtained by monitoring of all-cause mortality 3 years
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