ALS (amyotrophic lateral sclerosis) MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Amylyx Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion 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 sterilea must agree to use adequate birth controlb for the duration of the trial and 3 months after the last dose of AMX0035; a. 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. b. Acceptable contraception methods for use in this trial are: - Hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants; Barier 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; Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 286 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the long-term safety and tolerability of treatment with AMX0035;Secondary Objective: To assess the impact of long-term treatment with AMX0035 on survival Exploratory: To assess the impact of long-term treatment with AMX0035 on measures of ALS function and key events in disease progression;Primary end point(s): To assess the impact of long-term treatment with AMX0035 on measures of ALS function and key events in disease progression;Timepoint(s) of evaluation of this end point: After 108 weeks of treatment and FU visit (28 days after end of treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival of all-cause mortality 2. Ventilation free survival (defined as death, tracheostomy for respiratory distress or permanent non-invasive ventilation [>22 hours per day for 7 consecutive days]) Exploratory: Change from baseline in ALSFRS-R score at Week 108 2. To assess the incidence rate of the following significant ALS life-events over 108 weeks: a) Tracheostomy for assisted ventilation; b) Tracheostomy for management of secretions; c) Permanent Assisted Ventilation (PAV) [defined as >22 hours daily of mechanical ventilation for more than one week (7 days)]. The date of onset of PAV is the first day of the 7 days; d) Placement of feeding tube and clinically significant (i.e., requiring hospitalization or emergency department [ED] visit) complication/intervention (e.g., displacement, replacement, complications requiring surgical intervention); e) Placement of infusion port (in the subset of participants receiving concurrent IV edaravone) and clinically significant (i.e., requiring hospitalization or ED visit) complication/intervention (e.g., thrombosis, bleeding, infection, replacement); f) Incidence and duration of hospitalizations lasting more than 24 hours.;Timepoint(s) of evaluation of this end point: After 108 weeks of treatment and FU visit (28 days after end of treatment) | — |
Countries
Belgium, France, Germany, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Sweden, United Kingdom
Contacts
Public ContactLeslie Gransden
PPD, part of Thermo Fisher Scientific
Outcome results
None listed