Extension Study Evaluating The Safety And Tolerability of AMX0035

NCT05619783 | Completed Phase 3 FDA Drug

• 1 other identifier: A35-011
• Study Type: interventional
• Target: 352
• Locations: 11 countries
• Sites: 46

Brief Summary

The primary objective is to evaluate the safety and tolerability of AMX0035 over 108 weeks of open label treatment for participants previously enrolled in Study A35-004 (PHOENIX).

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• To assess the Incidence of Treatment-Emergent Adverse Events during treatment with AMX0035

  Incidence of all adverse events (AE)s; AEs leading to treatment discontinuation or study withdrawal, and all serious adverse events (SAE)s in participants treated with AMX0035

  108 weeks

Secondary Outcomes (1)

• To assess the impact of long-term treatment with AMX0035 on survival

  108 weeks

Study Arms (1)

Active

EXPERIMENTAL

All participants will be treated with oral (or feeding tube) AMX0035 (a fixed-dose combination of Sodium Phenylbutyrate (PB) and taurursodiol). All participants will take 2 sachets daily (one morning dose and one evening dose) starting on Day 1, for the duration of the study (if twice a day dosing is poorly tolerated, dosing interruptions and reductions are further discussed in section 6.3) AMX0035 will be supplied by Amylyx as a carton box containing approximately 1 month supply of single use sachets. Each AMX0035 sachet contains active ingredients in a powder formulation with 3 g PB and 1 g taurursodiol. AMX0035 powder is mixed with water and taken orally (or via feeding tube).

Drug: AMX0035

Interventions

AMX0035 DRUG

Combination of 3 g phenylbutyrate and 1 g taurursodiol

Also known as: RELYVRIO

Active

Eligibility Criteria

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

You may qualify if:

• Previous participation in Study A35-004 (PHOENIX), including completion of the randomized controlled phase through Week 48 (this timepoint may be upcoming at the time of screening). Participants who do not complete randomized-controlled phase through Week 48 for medical reasons may be included on a case-by-case basis, in consultation with the Sponsor;
• Capable of providing informed consent;
• Capable and willing to follow trial procedures including visits to the trial clinic, remote visits, and survival status reporting requirements;
• Women of childbearing potential (WOCBP; 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 trial and 3 months after the last dose of AMX0035;
• months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle-stimulating hormone (FSH) levels \> 40 mIU/ml (milli-international units per milliliter) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Acceptable contraception methods for use in this trial are:
• Hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants;
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm);
• Intrauterine device (IUD);
• Abstinence (no heterosexual sex);
• Unique partner who is surgically sterile (men) or not of childbearing potential (female).
• Women must not be pregnant or planning to become pregnant for the duration of the trial and 3 months after last dose of AMX0035;
• Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of AMX0035;
• Men must not plan to father a child or to provide sperm for donation for the duration of the trial and 3 months after the last dose of AMX0035

You may not qualify if:

• 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 estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2 normal (obtained within 12 weeks from first dose);
• Pregnant women 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;
• Currently enrolled in another trial (excluding Study A35-004 (PHOENIX)) involving use of an investigational therapy (or within 5 plasma half-lives) prior to first dose at Baseline Visit;
• Implantation of Diaphragm Pacing System (DPS);
• Currently or previously treated within the last 30 days (or 5 half-lives, whichever is longer) from first dose at the Baseline Visit or planned exposure during the treatment period to any prohibited medications listed in Section 6.7 of the protocol.

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead

Study Sites (46)

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

Gui de Chauliac

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

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

IRCCS - Ospedale San Raffaele

Milan, Italy

Location

University of Milan Medical School

Milan, Italy

Location

IRCCS - Istituto Auxologico italiano

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

Università degli Studi di Bari Aldo Moro

Tricase, 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 Universitario de Basurto

Bilbao, 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

The Walton Centre NHS Trust

Liverpool, United Kingdom

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 Clinical Research Team

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

• Lahar Mehta, MD

  Head, Global Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 17, 2022
• Study Start: December 29, 2022
• Primary Completion: October 16, 2024
• Study Completion: October 30, 2024
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

ES (6); SE (2); PL (2); DE (6); BE (1); FR (10); PT (1); NL (1); IT (10); GB (6); IE (1)