Extension Study Evaluating The Safety And Tolerability of AMX0035

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05619783
• Other study ID #: A35-011
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: December 29, 2022
• Est. completion date: August 2026

Study information

• Verified date: January 2024
• Source: Amylyx Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 600
• Est. completion date: August 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• AMX0035
Combination of 3 g phenylbutyrate and 1 g taurursodiol

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	Gui de Chauliac	Montpellier Cedex 5
France	CHU Nice	Nice
France	Hôpital de la Salpêtrière	Paris
France	Le Centre Hospitalier Régional Universitaire de Tours	Tours
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	IRCCS - Ospedale San Raffaele	Milan
Italy	University of Milan Medical School	Milan
Italy	IRCCS - Istituto Auxologico italiano	Milano
Italy	Azienda Ospedaliero Universitaria Di Modena	Modena
Italy	Università degli Studi della Campania Luigi Vanvitelli	Napoli
Italy	University of Padua	Padova
Italy	Università degli Studi di Bari Aldo Moro	Tricase
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 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
Sweden	Karolinska Institutet	Stockholm
Sweden	Umeå University Hospital	Umeå
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Amylyx Pharmaceuticals Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To assess the impact of long-term treatment with AMX0035 on survival	Overall survival of all-cause mortality; Ventilation free survival (defined as death, tracheostomy for respiratory distress or permanent non-invasive ventilation [>22 hours per day for 7 consecutive days])	108 weeks