Clinical trial NCT05619783: Extension Study Evaluating The Safety And Tolerability of AMX0035
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Amylyx Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-17
Enrollment: 352
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: To assess the Incidence of Treatment-Emergent Adverse Events during treatment with AMX0035
timeFrame: 108 weeks
Secondary outcomes:
measure: To assess the impact of long-term treatment with AMX0035 on survival
timeFrame: 108 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Bron
country: France
facility: Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer Cellule Mutualisée de Recherche Clinique (CMRC)
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied Service de Neurologie
city: Lille
country: France
facility: CHRU de Lille - Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Hôpitaux Universitaires de Marseille Timone
city: Montpellier Cedex 5
country: France
facility: Gui de Chauliac
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: Hôpital de la Salpêtrière
city: Tours
country: France
facility: Le Centre Hospitalier Régional Universitaire de Tours
city: Dresden
country: Germany
facility: Uniklinikum Dresden
city: Hannover
country: Germany
facility: Hannover Medical School
city: Jena
country: Germany
facility: Jena University Hospital
city: Mannheim
country: Germany
facility: Medizinische Fakultät Mannheim der Universität Heidelberg
city: Rostock
country: Germany
facility: University Medical Center Rostock
city: Ulm
country: Germany
facility: Ulm University Medical Centre
city: Dublin
country: Ireland
facility: Trinity College Dublin/Beaumont Hospital
city: Bari
country: Italy
facility: Università degli Studi di Bari Aldo Moro
city: Milano
country: Italy
facility: IRCCS - Istituto Auxologico italiano
city: Milan
country: Italy
facility: Centro Clinico NEMO
city: Milan
country: Italy
facility: IRCCS - Ospedale San Raffaele
city: Milan
country: Italy
facility: University of Milan Medical School
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena
city: Napoli
country: Italy
facility: Università degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: University of Padua
city: Tricase
country: Italy
facility: Università degli Studi di Bari Aldo Moro
city: Turin
country: Italy
facility: University of Torino
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Kraków
country: Poland
facility: Centrum Medyczne Linden
city: Warsaw
country: Poland
facility: City Clinic Warsaw
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitário Lisboa-Norte
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge-IDIBELL
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Madrid
country: Spain
facility: Hospital San Rafael
city: San Sebastián
country: Spain
facility: Biodonostia Health Research Institute; Hospital Universitario Donostia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Trust
city: London
country: United Kingdom
facility: King's College London
city: London
country: United Kingdom
facility: UCL Queen Square Institute of Neurology
city: Plymouth
country: United Kingdom
facility: University of Plymouth
city: Salford
country: United Kingdom
facility: Salford Royal Hospital Barnes Clinical Research Team
city: Sheffield
country: United Kingdom
facility: Sheffield Institute for Translational Neuroscience (SITraN)
Study officials:
affiliation: Head, Global Clinical Development
name: Lahar Mehta, MD
role: STUDY_DIRECTOR
References: