SAR443820 for ALS

(HIMALAYA Trial)

No longer recruiting at 144 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Seizures, Cognitive impairment, Psychiatric disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called SAR443820 for people with ALS, a condition that affects nerve cells in the brain and spinal cord, leading to muscle weakness. The trial will compare the effects of SAR443820, taken as a pill twice daily, to a placebo to determine its safety and effectiveness in treating ALS. Individuals who have experienced ALS symptoms for two years or less and can swallow pills might be suitable candidates for this study. Participants will receive either the treatment or a placebo for 24 weeks, with the option to continue receiving the treatment afterward. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if you are on riluzole, edaravone, or the combination of sodium phenylbutyrate and taurursodiol, as long as you are on a stable dose or approved schedule. However, you cannot be on strong or moderate CYP3A4 inhibitors or inducers before joining the trial.

Is there any evidence suggesting that SAR443820 is likely to be safe for humans?

Research has shown that SAR443820 is generally safe and well-tolerated. An initial study with humans found both single and repeated doses of SAR443820 to be safe, with participants experiencing few serious side effects. The treatment also demonstrated favorable pharmacokinetics, meaning the drug is absorbed, distributed, and processed in the body predictably and safely. Although more research is needed, early results are promising for the safety of SAR443820 in people with ALS. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Researchers are excited about SAR443820 for ALS because it offers a new approach to managing the disease. Unlike standard treatments like Riluzole and Edaravone, which primarily work to slow disease progression, SAR443820 targets a different pathway that could potentially address the underlying causes of nerve cell damage. This experimental drug is taken orally twice daily and may provide a more convenient treatment option with potentially broader effects on ALS symptoms. By focusing on novel mechanisms, SAR443820 has the potential to offer new hope for ALS patients.

What evidence suggests that SAR443820 might be an effective treatment for ALS?

Research has shown that SAR443820, which participants in this trial may receive, is designed to protect nerve cells by stopping harmful activities that cause inflammation and cell death. However, a previous study found that SAR443820 did not slow the progression of ALS as hoped. The main goal of that study was not achieved, as it didn't show the expected improvement in ALS symptoms. Despite this, the treatment's mechanism—aiming to prevent nerve damage—remains an area of interest for future research. While the initial results weren't promising, further studies may still find a way to make it effective. ^{2 4 5 6 7}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

Adults aged 18-80 with ALS, able to swallow tablets, and not severely ill from other conditions can join. They must have had symptoms for less than 2 years and a breathing capacity over 60% of expected. If taking riluzole, edaravone or sodium phenylbutyrate/taurursodiol (Relyvrio/Albrioza), doses must be stable for at least 4 weeks.

Inclusion Criteria

I am either not on edaravone or following its standard treatment schedule.

I am not on sodium phenylbutyrate and taurursodiol, or have been on it for 4 weeks.

I am not on riluzole, or I have been on a stable dose for at least 4 weeks.

Exclusion Criteria

Having central IV lines, such as a peripherally inserted central catheter (PICC), midline, or portacath lines

Serum albumin <3.5 g/dL

Bilirubin >1.5 × ULN unless the participant has documented Gilbert syndrome (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment (Part A)

Participants receive either SAR443820 or placebo in a double-blind manner

24 weeks

13 visits (in-person)

Open-label Extension (Part B)

Participants receive SAR443820 in an open-label manner to evaluate long-term safety and efficacy

80 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Not Applicable

Trial Overview The trial is testing SAR443820's effectiveness in slowing down ALS progression compared to a placebo. Participants are randomly assigned to either the drug or placebo group and will switch to open-label SAR443820 after the initial double-blind phase.

How Is the Trial Designed?

Group I: SAR443820 Experimental Treatment 1 Intervention

twice daily (BID) oral SAR443820

Group II: Placebo Placebo Group 1 Intervention

twice daily (BID) oral placebo

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

The phase 2 trial of AMX0035 demonstrated statistically significant effects in slowing ALS progression in a small sample of 137 patients, with a p-value of 3%, indicating potential efficacy.

Using Bayesian decision analysis, the optimal type I error rate for FDA approval of AMX0035 could be higher than the initial 3% if the therapy is at least 30% likely to be effective, suggesting a flexible approach to evaluating its approval based on patient needs and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating patient preferences and burden-of-disease in evaluating ALS drug candidate AMX0035: a Bayesian decision analysis perspective. Xu, Q., Cho, J., Ben Chaouch, Z., et al.[2023]

Riluzole is currently the only approved treatment for ALS, but its efficacy is mild, and despite extensive research, most clinical trials for new ALS treatments have not shown significant benefits.

Recent studies on oral masitinib and intravenous edaravone suggest they may be promising new therapies for ALS, with masitinib including a broader patient population in its trials compared to edaravone, which could impact their future use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment? Petrov, D., Mansfield, C., Moussy, A., et al.[2022]

Despite over 50 years of clinical trials for amyotrophic lateral sclerosis (ALS) involving various drugs, most trials have yielded negative results, highlighting the ongoing challenge of finding effective treatments.

The article emphasizes the need for improved trial design and implementation, particularly in selecting appropriate endpoints and surrogate markers for disease progression, to enhance the rigor and ethical standards of ALS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials in ALS: an overview. Turner, MR., Parton, MJ., Leigh, PN.[2013]

The study evaluated design modifications for phase 3 clinical trials in ALS, using data from 988 participants across 5 trials and 5,100 from population-based cohorts, which could reduce sample size by 30.5% and placebo exposure time by 35.4%.

By implementing flexible trial designs and prognostic survival models, the proposed strategies aim to enhance patient selection and minimize exposure to ineffective treatments, potentially leading to more effective ALS therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovating Clinical Trials for Amyotrophic Lateral Sclerosis: Challenging the Established Order. van Eijk, RPA., Nikolakopoulos, S., Roes, KCB., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05237284

Phase 2 Study for SAR443820 in Participants With ... The study was terminated as its Part A did not meet the primary endpoint. Phase 2 Study for SAR443820 in Participants With Amyotrophic Lateral Sclerosis (ALS) ( ...

2. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/10/34789-SAR443820-for-Amyotrophic-Lateral-Sclerosis-V1.0-OCT2023-NON-CONF.pdf

SAR443820 for treating amyotrophic lateral sclerosis (ALS) SAR443820 prevents damage to nerve cells and brain cell death caused by RIPK1 activities which causes inflammatory damage and brain cell death.

3. congress.sanofimedical.com congress.sanofimedical.com/s3fs-public/2023-10/UPDATED---NEALS%202023_Himalaya%20baseline%20characteristics_Final%20Version.pdf?VersionId=LxHxbQY4VLO1S6gJQeumaNkvSUoxaY92

A Phase 2 Trial of RIPK1 Inhibitor SAR443820 in Adult ... The use of riluzole, edaravone, or the combination of sodium phenylbutyrate and taurursodiol is based on randomization stratifi cations from ...

4. alsnewstoday.com alsnewstoday.com/news/denali-therapy-candidate-fails-slowing-als-progression-trial/

Denali therapy candidate fails to slow ALS progression in trial Denali's oral therapy candidate SAR443820 did not slow ALS progression in a Phase 2 clinical trial, failing to meet the study's main goal.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772668/

Safety, pharmacokinetics, and target engagement of a brain ... These results support further development of SAR443820 in phase II trials in amyotrophic lateral sclerosis (NCT05237284) and multiple sclerosis (NCT05630547).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38010108/

Safety, pharmacokinetics, and target engagement of a ... SAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1).

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000202201

First-in-Human Study of Safety, Tolerability, ... The first-in-human study demonstrated that single and repeated SAR443820 doses were generally safe and well-tolerated, with favorable pharmacokinetics.