Clinical trial NCT05021536: Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Safety and Efficacy of AMX0035 Versus Placebo for 48-week Treatment of Adult Patients With Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Amylyx Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-25
Enrollment: 664
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change
timeFrame: 48 weeks
Secondary outcomes:
measure: Participant Quality of Life (QOL)
timeFrame: 48 weeks
measure: Assess Long-Term Survival
timeFrame: 3 years from LPI
measure: Rate of Decline in Slow Vital Capacity (SVC)
timeFrame: 48 weeks
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change
timeFrame: 24 weeks
measure: Number of Participants With Adverse Events
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Augusta University Neuroscience Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine Outpatient Center
state: Maryland
city: Boston
country: United States
facility: Healey & AMG Center for ALS Research at Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin Healthcare Research Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Somnos Clinical Research
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers University
state: New Jersey
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Lewis Katz School of Medicine at Temple University
state: Pennsylvania
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Henrico
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Bron
country: France
facility: Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer Cellule Mutualisée de Recherche Clinique (CMRC)
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied Service de Neurologie
city: Lille
country: France
facility: CHRU de Lille - Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Hôpitaux Universitaires de Marseille Timone
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: Hôpital de la Salpêtrière
city: Tours
country: France
facility: Le Centre Hospitalier Régional Universitaire de Tours
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: Uniklinikum Dresden
city: Hannover
country: Germany
facility: Hannover Medical School
city: Jena
country: Germany
facility: Jena University Hospital
city: Mannheim
country: Germany
facility: Medizinische Fakultät Mannheim der Universität Heidelberg
city: Rostock
country: Germany
facility: University Medical Center Rostock
city: Ulm
country: Germany
facility: Ulm University Medical Centre
city: Dublin
country: Ireland
facility: Trinity College Dublin/Beaumont Hospital
city: Bari
country: Italy
facility: Università degli Studi di Bari Aldo Moro
city: Milan
country: Italy
facility: Centro Clinico NEMO
city: Milan
country: Italy
facility: University of Milan Medical School
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena
city: Napoli
country: Italy
facility: Università degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: University of Padua
city: Turin
country: Italy
facility: University of Torino
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Kraków
country: Poland
facility: Centrum Medyczne Linden
city: Warsaw
country: Poland
facility: City Clinic Warsaw
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitário Lisboa-Norte
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge-IDIBELL
city: Madrid
country: Spain
facility: Hospital San Rafael
city: San Sebastián
country: Spain
facility: Biodonostia Health Research Institute; Hospital Universitario Donostia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: London
country: United Kingdom
facility: King's College London
city: London
country: United Kingdom
facility: UCL Queen Square Institute of Neurology
city: Plymouth
country: United Kingdom
facility: University of Plymouth
city: Salford
country: United Kingdom
facility: Salford Royal Hospital Barnes
city: Sheffield
country: United Kingdom
facility: Sheffield Institute for Translational Neuroscience (SITraN)
Study officials:
affiliation: Amylyx Pharmaceuticals
name: Amylyx Study Director
role: STUDY_DIRECTOR
References: