Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicentre Trial to Evaluate the Safety and Efficacy of AMX0035 Versus Placebo for 48-week Treatment of Adult Patients with Amyotrophic Lateral Sclerosis (ALS)
UK Chief Investigator
Professor Chris McDermott
The purpose of this study is to find out if the study drug AMX0035 is safe for the treatment of ALS, and how well it works to determine if AMX0035 can slow down worsening of the disease over 48 weeks compared to placebo in adult patients. Also, AMX0035 is being studied to understand the effect on disease progression in participants with ALS. The sponsor also wants to explore whether the use of AMX0035 influences the burden on the caregiver.
Approximately 600 subjects with ALS and their caregivers are expected to participate. The study takes place in approximately 12 countries (55 sites) total in Europe and in the US.
Participants will first receive an oral dose of the study drug once a day in the morning (AMX0035 or placebo; one sachet per day) for approximately 14-21 days. For participants who tolerate the treatment, the dose will then be escalated to twice a day oral dosing in the morning and evening for the remainder of 48-week treatment duration.
Each participant will be in the trial for approximately 1 year.
Inclusion / exclusion criteria
Key inclusion criteria:
1. Male or female, at least 18 years of age
2. Diagnosis of ALS (definite or clinically probable), made by a physician who is experienced with management of ALS, as defined by the World Federation of Neurology revised El Escorial criteria
3. Time since onset of first symptom of ALS should be <24 months prior to randomization
4. If the participant is to be treated with riluzole and/or edaravone during the course of the trial, then treatment with riluzole and/or edaravone was, at the time of the screening visit, started and maintained at a stable regimen for at least 14 days for riluzole and/or for a full treatment cycle for edaravone
5. Capable of providing informed consent
6. Capable and willing to follow trial procedures including visits to the trial clinic and visit requirements
7. Women of childbearing potential must agree to use adequate birth control for the duration of the trial and 3 months after the last dose of study drug
8. Women must not be pregnant or planning to become pregnant for the duration of the trial and 3 months after last dose of study drug
9. Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of study drug
10. 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 study drug;
Key exclusion criteria:
1. Presence of tracheostomy or PAV
2. Slow Vital Capacity (SVC) less than 55%
3. History of known allergy to phenyl butyrate or bile salts
4. 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)
5. Renal insufficiency as defined by eGFR <60 mL/min/1.73m2 (obtained within 12 weeks from first dose)
6. Pregnant women (confirmed by a pregnancy test within 7 days of first dose) or women currently breastfeeding
7. 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
8. History of Class III/IV heart failure (per New York Heart Association – NYHA)
9. Participant under severe salt restriction where the added salt intake due to treatment would put the participant at risk, in the Investigator clinical judgment
10. 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
11. 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
12. Previous treatment for ALS with cellular therapies or gene therapies
13. Currently enrolled in another trial involving use of an investigational therapy
14. Previous treatment with PB or taurursodiol within 30 days from Screening
15. Implantation of Diaphragm Pacing System (DPS)
16. Currently or previously treated within the last 30 days or planned exposure to any prohibited medications listed in the protocol.
Open to recruitment
Royal Hallamshire Hospital, Sheffield Opening soon
King's College Hospital, London Opening soon
University College Hospitals London
Derriford Hospital, Plymouth
The Walton Centre, Liverpool Opening soon
More UK sites opening soon.
Patients with MND
Up to 600 participants globally (25 participants in the UK)
Actual opening date: 01 July 2022
Recruitment planned end date: 28 October 2022
Amylyx Pharmaceuticals, Inc.
Amylyx Pharmaceuticals, Inc.
Interventional, randomised controlled trial
Intervention (if applicable)
Drug: Tauroursodeoxycholic acid (TUDCA) and sodium phenylbutyrate (PB) in combination - AMX0035
Phase (if applicable)
Primary outcome measures
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) slope change and survival
Number of participants with Adverse Events (AEs)
Number of participants in each group able to remain on study drug until planned discontinuation
Secondary outcome measures
Rate of decline in slow vital capacity (SVC)
Participant Quality of Life (QOL)
Decline in King's and MiToS stages
Participant health status
Assess long-term survival
Publications / Results reports
Links will be provided when papers are published.