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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asociacion Instituto Biogipuzkoa

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

25 Nov 2025 → ongoing

Decision date (initial)

2025-04-21

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III (ICI19/00061)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the clinical efficacy and safety of the combination of NAC and EH301 compared to placebo on disease progression in ambulatory patients diagnosed with ALS via the ALS Functional Rating Scale-Revised (ALSFRS-R) score.

Secondary objectives 5

1. To determine the effect of the combination of NAC and EH301 as adjuvant treatment to Riluzole in comparison with placebo on muscle strength.
2. To determine the effect of the combination of NAC and EH301 compared to placebo on survival.
3. To evaluate the effect of the combination of NAC and EH301 compared to placebo on health-related quality of life.
4. To evaluate the efficacy of the combination of NAC and EH301 compared to placebo on disease progression.
5. To evaluate the impact of the combination of NAC and EH301 on the rate of Nfl in serum and CSF compared with placebo.

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis (ALS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients diagnosed with ALS according to Gold Coast criteria.
2. Duration of disease ≤ 18 months
3. Males and females aged 18 to 75 years
4. ALSFRS-R total score ≥ 30 for all 12 categories
5. Forced vital capacity (FVC) ≥70%
6. Participant must be treated 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 protocol requirements during the study
8. Sign written informed consent prior to any study-related procedures
9. Acceptance by the women of the use of contraceptive measures 30 days prior to taking the nutraceutical and investigational drug and throughout the study. Acceptable contraceptive method means: non-hormonal intrauterine device (IUD), barrier method (condom), bilateral tubal occlusion, vasectomized partner (provided the partner has been provided with a medical evaluation of the success of the surgery), or abstinence from sexual intercourse, in women of childbearing age (e.g., women who are not postmenopausal or have not been surgically sterilized).

Exclusion criteria 17

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 cardiac disease
6. Moderate to severe pulmonary disease, such as emphysema, stage III-IV COPD
7. Chronic uncontrolled asthma
8. Active cancer
9. Any metabolic, neoplastic, physically or mentally debilitating disease that could put the subject at risk or may interfere with the results of the study
10. Genetically confirmed mitochondrial disease
11. Tracheostomized and/or gastrostomized patients
12. Participation in any clinical trial with investigational product in the within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
13. Any clinically significant laboratory abnormalities that may directly affect compliance or safety
14. Allergy to NAC or any excipient of either the investigational drug or the nutraceutical EH301
15. Patients with short life expectancy as judged by the investigator
16. [Females only] Pregnancy or lactation for women of childbearing age (i.e., <2 years postmenopausal or not surgically sterile)
17. Patient is unwilling to use highly effective contraceptive methods during.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Changes in the ALSFRS-R scale.
2. Time to progression of patients suffering a 20% reduction in the ALSFRS-R scale 3.

Secondary endpoints 7

1. Muscle strength measured by manual dynamometry.
2. Survival.
3. Quality of life measured by the ALSAQ-40 scale.
4. Respiratory function through the percentage of forced capacity (%FVC).
5. Time elapsed until gastrostomy.
6. Combined assessment of function and survival (CAFS).
7. Nfl rate in CSF and changes in serum Nfl rate.

Investigational products

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

Test 1

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asociacion Instituto Biogipuzkoa

Sponsor organisation

Asociacion Instituto Biogipuzkoa

Address

Pasealeku Doct. Begiristain S/N

City

Donostia

Postcode

20014

Country

Spain

Scientific contact point

Organisation

Asociacion Instituto Biogipuzkoa

Contact name

Plataforma de Investigación Clínica

Public contact point

Organisation

Asociacion Instituto Biogipuzkoa

Contact name

Plataforma de Investigación Clínica

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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