SAR443820 for ALS

(HIMALAYA Trial)

Recruiting at 130 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

305 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests SAR443820, a pill taken regularly, in adults aged 18-80 with ALS. It aims to see if the new medication helps ALS patients and is safe over time.

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.

What data supports the effectiveness of the drug SAR443820 for ALS?

Research on a similar drug, masitinib, showed it could slow the progression of ALS by 27% in certain patients when added to the standard treatment, riluzole. This suggests that drugs targeting similar pathways might also be effective for ALS. ^{1 2 3 4 5}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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%)

Serum albumin <3.5 g/dL

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical trials in ALS: an overview. [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment? [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Innovating Clinical Trials for Amyotrophic Lateral Sclerosis: Challenging the Established Order. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Incorporating patient preferences and burden-of-disease in evaluating ALS drug candidate AMX0035: a Bayesian decision analysis perspective. [2023]