A Phase IIIb, Open Label Extension Study Evaluating The Safety And Tolerability of AMX0035 Up To 108 Weeks In Adult Participants With Amyotrophic Lateral Sclerosis (ALS) Previously Enrolled In Study A35-004 (PHOENIX)

Study Purpose:

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).

Study Status:

Not yet recruiting

Disease:

Amyotrophic Lateral Sclerosis

Study Type:

Interventional

Type of Intervention:

Drug

Intervention Name:

AMX0035

Placebo:

No

Phase:

Phase 3

Study Chair(s)/Principal Investigator(s):

Lahar Mehta, MD, Head, Global Clinical Development

Clinicaltrials.gov ID:

NCT05619783

Neals Affiliated?

No

Coordinating Center Contact Information

Amylyx Trial Operations / email hidden; JavaScript is required / 857 320 6222

Full Study Summary:

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).

Study Sponsor:

Amylyx Pharmaceuticals Inc.

Estimated Enrollment:

600

Estimated Study Start Date:

11 / 01 / 2022

Estimated Study Completion Date:

08 / 01 / 2026

Posting Last Modified Date:

11 / 17 / 2022

Date Study Added to neals.org:

11 / 17 / 2022

Minimum Age:

18 Years

Maximum Age:

N/A

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.

University Hospitals Leuven

Leuven
Belgium

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
France

Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer Cellule Mutualisée de Recherche Clinique (CMRC)

Bron
France

University Medical Center Rostock

Rostock
Germany

Ulm University Medical Centre

Ulm
Germany

Uniklinikum Dresden

Dresden
Germany

Medizinische Fakultät Mannheim der Universität Heidelberg

Mannheim
Germany

Jena University Hospital

Jena
Germany

Hannover Medical School

Hannover
Germany

Trinity College Dublin/Beaumont Hospital

Dublin
Ireland

University of Torino

Turin
Italy

University of Padua

Padova
Italy

Università degli Studi della Campania Luigi Vanvitelli

Napoli
Italy

Azienda Ospedaliero Universitaria Di Modena

Modena
Italy

University of Milan Medical School

Milan
Italy

IRCCS - Ospedale San Raffaele

Milan
Italy

Centro Clinico NEMO

Milan
Italy

Università degli Studi di Bari Aldo Moro

Bari
Italy

University Medical Center Utrecht

Utrecht
Netherlands

Centrum Medyczne Linden

Kraków
Poland

City Clinic Warsaw

Warsaw
Poland

Centro Hospitalar Universitário Lisboa-Norte

Lisbon
Portugal

Hospital Universitario y Politécnico La Fe

Valencia
Spain

Biodonostia Health Research Institute; Hospital Universitario Donostia

San Sebastián
Spain

Hospital San Rafael

Madrid
Spain

Hospital Universitario de Basurto

Bilbao
Spain

Hospital Universitari de Bellvitge-IDIBELL

Barcelona
Spain

Hospital del Mar

Barcelona
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