EH-301 and N-acetylcysteine with Riluzole for early ALS

A Phase II, Single-center, Randomized Double Blind, Placebo Controlled Study to Evaluate the Effect of the Combined Therapy of EH-301 and N-acetylcysteine Together With Riluzole in Ambulant Patients Diagnosed With Amyotrophic Lateral Sclerosis (ALS)

This will test whether adding EH-301 plus N-acetylcysteine to standard Riluzole can slow down or improve symptoms in people with ALS.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Biogipuzkoa Health Research Institute (Academic / other)
• Locations: 1 site (San Sebastián, Guipuzcoa)
• Trial ID: NCT07414212 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 1/2 study gives people with recent-onset ALS either the active combination (EH-301 + N-acetylcysteine) or matching placebos for 6 months while they continue Riluzole. Researchers will measure changes in function using the ALSFRS-R and monitor safety with regular clinic visits, tests, and labs. After the 6-month blinded phase, participants may join a 6-month open-label extension where everyone receives the active treatment. Enrollment focuses on patients with disease duration ≤18 months, ALSFRS-R ≥30, and FVC ≥70%.

Who should consider this trial

Good fit: Adults 18–75 years with ALS diagnosed by Gold Coast criteria, disease duration ≤18 months, ALSFRS-R ≥30, FVC ≥70%, and already taking Riluzole are the intended participants.

Not a fit: Patients with more advanced disease, lower lung function (FVC <70%), longer disease duration, or not taking Riluzole are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could slow disease progression or improve daily functioning compared with Riluzole alone.

How similar studies have performed: N-acetylcysteine has been studied in ALS with mixed and limited results, and combining it with EH-301 is a novel approach that has not yet demonstrated clear clinical success.

Eligibility criteria

Inclusion Criteria:

1. Patients diagnosed with ALS according to the Gold Coast criteria;
2. Disease duration ≤ 18 months;
3. Men and women aged 18 to 75 years;
4. Total ALSFRS-R score ≥ 30 for all 12 categories;
5. Forced vital capacity (FVC) ≥70%;
6. The participant must receive treatment with Riluzole (50 mg twice daily) for ≥30 days prior to Day 1 (Visit 2) and is expected to remain on that dose until the final study visit.
7. Willingness and ability of the patient to comply with the requirements of the protocol during the study;
8. Sign written informed consent prior to any study-related procedure;
9. Acceptance by women to use at least one highly effective method of contraception during the study 30 days prior to taking the nutraceutical and investigational drug and throughout the study. The following are considered highly effective contraceptive methods:

   * Combined hormonal methods (oral, patches, injectables, or implants).
   * Hormonal or copper intrauterine devices (IUDs).
   * Previous surgical sterilization (bilateral tubal ligation).
   * Total sexual abstinence when consistent with the patient's usual lifestyle.
10. Acceptance by men included in the study of the use of condoms in combination with an effective contraceptive method used by their female partner of childbearing age during treatment.

Exclusion Criteria:

1. Presence of other neurodegenerative diseases;
2. Significant cognitive impairment and/or dementia;
3. Any psychiatric illness that could interfere with the study;
4. Use of dietary supplements with high doses of vitamin B3 in the 30 days prior to inclusion in the study;
5. Severe heart disease;
6. Moderate to severe lung disease, such as emphysema, stage III-IV COPD;
7. Uncontrolled chronic asthma;
8. Active cancer;
9. Any metabolic, neoplastic, physically or mentally debilitating disease that could put the subject at risk or interfere with the study results;
10. Genetically confirmed mitochondrial disease;
11. Tracheostomized and/or gastrostomized patients;
12. Participation in any clinical trial with an investigational product within 30 days or five half-lives of the previous agent, whichever is longer, prior to dosing;
13. Any clinically significant laboratory abnormality that could directly affect compliance or safety;
14. Allergy to NAC or any excipient, either in the investigational drug or in the EH301 nutraceutical;
15. Patients with a short life expectancy in the investigator's judgment.
16. \[Women only\] Pregnancy or breastfeeding for women of childbearing potential (i.e., \<2 years postmenopausal or not surgically sterile);
17. The participant is unwilling to use highly effective contraception during the study.

Where this trial is running

San Sebastián, Guipuzcoa

• Hospital Universitario Donostia — San Sebastián, Guipuzcoa, Spain (Recruiting)

Study contacts

• Study coordinator: Lara Alameda Calvo

Conditions Amyotrophic Lateral Sclerosis; Acetylcysteine; EH301; ALSFRS-R; ALS; NAC; Hospital Universitario Donostia; Biogipuzkoa