NB-4746-201 study

This study investigates whether the investigational drug NB-4746 is safe and how well it is tolerated by people with ALS. Another objective of the study include assessment of how NB-4746 affects different biomarkers and clinical measures relevant to ALS compared to placebo. The drug is administered orally via a capsule.

The investigational compound NB-4746

SARM1 is an enzyme known to be enriched in part of the neurons of the nervous system and plays a role in the destruction of nerve cells. Increased activity of SARM1 has been associated with degeneration of specifics parts of the neuron and ALS-like symptoms, such as motor dysfunction. The investigational compound NB-4746 inhibits the activity of SARM1, conferring protection against degeneration of specific parts of the neuron.

NB-4746 must be administered orally through capsules, twice a day.

Study design

This study is a Phase 1b/2 study, both studies with a different set-up and treatment groups. The main goal of a Phase 1b/2 study is to see whether a new drug is safe. The study is designed as a randomized, double-blind, placebo-controlled trial. A placebo is a substance that looks like NB-4746 but has no active ingredients. Researchers use a placebo to see if a research medicine works better or is safer than not taking anything at all. Double-blind means you will be randomized (by chance, like flipping a coin) to either the study drug NB-4746 or placebo, where neither you nor your doctor know that you receive medication or placebo

Phase 1b

Within phase 1b, there will be a total of 24 people with ALS, who are allocated evenly among three treatment groups:

1. NB-4746, 100 mg twice daily (two capsules of 50mg per dose)
2. NB-4746, 50 mg twice daily (two capsules of 25mg per dose)
3. Placebo, twice daily (two placebo capsules per dose)

On day 1, the study starts with the first dose in the clinic. Participants will continue taking the capsules twice a day for 28 days. Clinic visits are planned for days 7, 14, 21, and 28. After 28 days, there is a 1-week safety follow-up period. On day 35 there is an End of Study visit. Eligible participants may enter an open-label extension (OLE) once a dose has been selected by the Safety Review Committee.

Phase 2

Within phase 2, there will be a total of 56 people with ALS, who are allocated evenly among two treatment groups:

1. NB-4746, Dose TBD based on phase 1b twice daily (two TBD-mg NB-4746 capsules per dose)
2. Placebo, twice daily (two placebo capsules per dose)

On day 1, the study starts with the first dose in the clinic. Participants will continue taking the capsules twice a day for 12 weeks. Clinic visits are planned for weeks 4, 8, and 12. After 12 weeks, there is a 4-week safety follow-up period. At week 16, there is an End of Study visit. Eligible participants may enter an open-label extension (OLE) after week 16, until they reach a total of 52 weeks.

Open-Label Extension (OLE)

Open-label means that nobody receives placebo, but all participants will receive the study drug NB-4746.The OLE will allow participants to continue study treatment for a total of 52 weeks. All participants will receive NB-4746 BID at a dose of recommended by the Safety Review Committee.

Can I participate in the study?

The main criteria to participate in this study are:

• Age between 18 and 80 years
• Lung function (SVC) ≥ 60%
• You are able to swallow capsules
• If you’re currently using ALS medication, a stable dose of this medication for at least 60 days prior to study participation is required

Phase 1b:

• Onset of first symptom leading to ALS diagnosis occurred ≤ 48 months prior to the first study visit

Phase 2:

• Onset of first symptom leading to ALS diagnosis occurred ≤ 24 months prior to the first study visit 2

Note: This list is not exhaustive, but these are the main criteria.

Registration and more information

If you are interested in participating in the NB-4746-201 study, please contact one of the participating TRICALS centres below (contact details can be found by clicking on ‘More about this centre’). Make use of the contact form on each Centre detail page, or when contacting the centre of your choice by email or telephone, please provide your full name, your date of birth and the date of onset of symptoms. The centre can provide you with more information about the study and/or inclusion criteria and answer any questions you may have. If you experience difficulty contacting a centre, you may reach out directly to the TRICALS operational team at info@tricals.org for support in this process.

More information about the study can be found at