Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment

Amyotrophic Lateral Sclerosis Clinical Trial

— Phoenix  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05021536
• Other study ID #: A35-004
• Status: Active, not recruiting
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

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