A study to investigate the safety and efficacy of AMX0035 in patients with Amyotrophic Lateral Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amylyx Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Dec 2021 → 14 Jan 2025

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amylyx Pharmaceuticals Inc.

External identifiers

EU CT number

2023-508511-23-00

EudraCT number

2021-000250-26

ClinicalTrials.gov

NCT05021536

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Therapy, Pharmacokinetic, Others

To assess the impact of AMX0035 treatment compared to placebo on disease progression over 48 weeks in adult patients with ALS.

Secondary objectives 4

1. To assess patient quality of life during treatment with AMX0035 compared to placebo
2. To assess the impact of AMX0035 compared to placebo on overall survival
3. To assess the impact of AMX0035 compared to placebo on Slow Vital Capacity (SVC)
4. To assess the impact of AMX0035 treatment compared to placebo on disease progression over 24 weeks in adult patients with ALS

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis (ALS)

Study design 4 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female, at least 18 years of age.
2. Diagnosis of ALS (clinically 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.
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 baseline visit, previously 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, remote visits, and status reporting requirements.
7. 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 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.

Exclusion criteria 16

1. Presence of tracheostomy or PAV.
2. Slow Vital Capacity less than 55%.
3. History of known allergy to Phenylbutyrate or bile salts.
4. Abnormal liver function
5. Renal insufficiency as defined by estimated glomerular filtration rate (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 judgment 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
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) 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 on 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
16. Currently or previously treated within the last 30 days or planned exposure to any prohibited medications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in ALSFRS-R total score at Week 48 adjusting for mortality

Secondary endpoints 4

1. Change from baseline in ALSAQ-40 Total Score at Week 48
2. Overall survival
3. Change from baseline to Week 48 of the percent predicted SVC using in clinic visits
4. Change from baseline in ALSFRS-R total score at Week 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amylyx Pharmaceuticals Inc.

Sponsor organisation

Amylyx Pharmaceuticals Inc.

Address

43 Thorndike Street

City

Cambridge

Postcode

02141-1764

Country

United States

Scientific contact point

Organisation

Amylyx Pharmaceuticals Inc.

Contact name

Regulatory Affairs

Public contact point

Organisation

Amylyx Pharmaceuticals Inc.

Contact name

Regulatory Affairs

Third parties 6

Locations

10 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications