Extension Study Evaluating The Safety And Tolerability of AMX0035

NCT ID: NCT05619783

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-29
• Study Completion Date: 2024-10-30

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).

Detailed Description

All participants will receive open-label treatment with AMX0035, starting on Day 1 with twice a day oral dosing (once in the morning and once in the evening) for the duration of the study. After the Baseline Visit (Day 1), enrolled participants will complete visits approximately every 12 weeks (± 2 weeks), until Week 108 or the end of treatment (EOT) visit, followed by a safety follow-up approximately 28 days after the last dose. A survival follow-up assessment will be completed every 12 weeks following the EOT visit until time of death or end of study (EOS).

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active

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).

Group Type: EXPERIMENTAL

AMX0035

Intervention Type: DRUG

Combination of 3 g phenylbutyrate and 1 g taurursodiol

Interventions

AMX0035

Combination of 3 g phenylbutyrate and 1 g taurursodiol

Intervention Type: DRUG

Other Intervention Names

RELYVRIO

Eligibility Criteria

Inclusion Criteria

1. 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;

2. Capable of providing informed consent;

3. Capable and willing to follow trial procedures including visits to the trial clinic, remote visits, and survival status reporting requirements;

4. 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;

1. 12 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.

2. 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).

5. Women must not be pregnant or planning to become pregnant for the duration of the trial and 3 months after last dose of AMX0035;

6. Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of AMX0035;

7. 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

Exclusion Criteria

1. History of known allergy to phenyl butyrate or bile salts;

2. 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);

3. Renal insufficiency as defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 normal (obtained within 12 weeks from first dose);

4. Pregnant women or women currently breastfeeding;

5. 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;

6. History of Class III/IV heart failure (per New York Heart Association - NYHA);

7. Participant under severe salt restriction where the added salt intake due to treatment would put the participant at risk, in the Investigator clinical judgment;

8. 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;

9. 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;

10. 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;

11. Implantation of Diaphragm Pacing System (DPS);

12. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amylyx Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lahar Mehta, MD

Role: STUDY_DIRECTOR

Head, Global Clinical Development

Locations

University Hospitals Leuven

Leuven, , Belgium

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

Gui de Chauliac

Montpellier, , France

CHU Nice

Nice, , France

Hôpital de la Salpêtrière

Paris, , France

Le Centre Hospitalier Régional Universitaire de Tours

Tours, , France

Uniklinikum Dresden

Dresden, , Germany

Hannover Medical School

Hanover, , 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, , Germany

Trinity College Dublin/Beaumont Hospital

Dublin, , Ireland

Università degli Studi di Bari Aldo Moro

Bari, , Italy

Centro Clinico NEMO

Milan, , Italy

IRCCS - Ospedale San Raffaele

Milan, , Italy

University of Milan Medical School

Milan, , Italy

IRCCS - Istituto Auxologico italiano

Milan, , Italy

Azienda Ospedaliero Universitaria Di Modena

Modena, , Italy

Università degli Studi della Campania Luigi Vanvitelli

Napoli, , Italy

University of Padua

Padua, , Italy

Università degli Studi di Bari Aldo Moro

Tricase, , Italy

University of Torino

Turin, , Italy

University Medical Center Utrecht

Utrecht, , Netherlands

Centrum Medyczne Linden

Krakow, , Poland

City Clinic Warsaw

Warsaw, , Poland

Centro Hospitalar Universitário Lisboa-Norte

Lisbon, , Portugal

Hospital del Mar

Barcelona, , Spain

Hospital Universitari de Bellvitge-IDIBELL

Barcelona, , Spain

Hospital Universitario de Basurto

Bilbao, , Spain

Hospital San Rafael

Madrid, , Spain

Biodonostia Health Research Institute; Hospital Universitario Donostia

San Sebastián, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Karolinska Institutet

Stockholm, , Sweden

Umeå University Hospital

Umeå, , Sweden

The Walton Centre NHS Trust

Liverpool, , 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 Clinical Research Team

Salford, , United Kingdom

Sheffield Institute for Translational Neuroscience (SITraN)

Sheffield, , United Kingdom

Countries

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

Other Identifiers

A35-011

Identifier Type: -

Identifier Source: org_study_id