Multiple Treatments for ALS

Recruiting at 81 trial locations

Overseen By HEALEY Center for ALS at Massachusetts General Hospital

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2 & 3

Sponsor: Merit E. Cudkowicz, MD

Must be taking: Riluzole, Edaravone

Must not be taking: Investigational treatments

Disqualifiers: Unstable medical condition, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

1500 Participants Needed

Trial Summary

What is the purpose of this trial?

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS.

Will I have to stop taking my current medications?

The trial requires that you either not take riluzole or be on a stable dose for at least 30 days before starting. For edaravone, you must have completed at least one cycle before starting. Other medications are not specified, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug ABBV-CLS-7262, Fosigotifator, ABBV-CLS-7262, Fosigotifator sodium tromethamine, CNM-Au8, Pridopidine, SLS-005 Trehalose, Verdiperstat, AZD3241, BHV-3241, Zilucoplan, Zilbrysq, Zilucoplan for ALS?

The drug CNM-Au8 has shown potent therapeutic effects in clinical trials for ALS, as mentioned in the review of new developments in ALS treatments from 2020 to 2022. Additionally, SLS-005 (Trehalose) is among the drugs being tested in phase 3 studies, indicating ongoing research into its potential effectiveness for ALS. ^{1 2 3 4 5}

Is Zilucoplan safe for human use?

Zilucoplan has been studied for the treatment of generalized myasthenia gravis and has been approved in several countries, indicating it is considered safe for use in humans for this condition. ^{6 7 8 9 10}

What makes the drug ABBV-CLS-7262 unique for treating ALS?

The drug ABBV-CLS-7262 is unique for treating ALS because it is part of a combination of multiple treatments, including CNM-Au8, Pridopidine, SLS-005 Trehalose, Verdiperstat, and Zilucoplan, which may offer a novel approach by targeting different pathways involved in the disease. This multi-drug strategy could potentially address various aspects of ALS, unlike traditional treatments that often focus on a single mechanism. ^{11 12 13 14 15}

Research Team

Merit Cudkowicz, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults with ALS, diagnosed as per El Escorial criteria, who can consent and follow study procedures. They must have a vital capacity over 50%, be within 36 months of symptom onset, and able to swallow. Participants on riluzole or edaravone must be on stable doses; those not taking these drugs may join. Exclusions include significant unstable medical conditions, certain lab abnormalities, active cancer (with exceptions), pregnancy/breastfeeding without contraception use, recent investigational drug use for ALS.

Inclusion Criteria

My ALS-related weakness started less than 3 years ago.

I have not taken riluzole, or I have been on a stable dose for at least 30 days.

I have never taken edaravone or have completed at least one cycle before the screening.

Exclusion Criteria

I have no active cancer except for certain skin, cervical, or prostate cancers treated over 3 years ago.

I am a man who can father children and agree to use contraception during and after the trial as required.

Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant, according to SI's judgment (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, or clinically significant laboratory abnormality or EKG changes)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the active investigational product or placebo in a 3:1 ratio

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• ABBV-CLS-7262
• CNM-Au8
• Pridopidine
• SLS-005 Trehalose
• Verdiperstat
• Zilucoplan

Trial Overview The HEALEY ALS Platform Trial tests multiple potential treatments for ALS simultaneously: Zilucoplan, Verdiperstat, CNM-Au8, Pridopidine, SLS-005 Trehalose, ABBV-CLS-7262 and DNL343. It's designed to evaluate the safety and effectiveness of these investigational products in slowing down or stopping disease progression.

Participant Groups

Group I: Regimen G - DNL343 Experimental Treatment 1 Intervention

Participants are randomized to receive either active DNL343 or matching placebo.

Group II: Regimen F- ABBV-CLS-7262 Experimental Treatment 1 Intervention

Participants are randomized to receive either active ABBV-CLS-7262 or matching placebo.

Who Is Running the Clinical Trial?

Merit E. Cudkowicz, MD

Lead Sponsor

Trials

8

Recruited

2,900+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Findings from Research

A review of 53 new drugs evaluated in clinical trials for ALS from 2020 to 2022 identified five promising candidates, including AMX0035, which has recently been approved by the FDA, marking it as the third drug approved for ALS treatment after riluzole and edaravone.

The review categorized these drugs into eight mechanistic groups, highlighting a diverse range of approaches being explored to combat ALS, with 13 drugs currently in phase 3 trials, indicating ongoing efforts to find more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. Jiang, J., Wang, Y., Deng, M.[2022]

Sodium phenylbutyrate-taurursodiol (PB-TURSO) has been shown to be safe and effective for treating amyotrophic lateral sclerosis (ALS), leading to its conditional approval in Canada and full approval in the USA after the CENTAUR trial, which was a randomized, double-blind, multicenter study.

The ongoing phase 3 PHOENIX trial will further evaluate the safety and efficacy of AMX0035, a combination of PB and TURSO, but its high annual cost of $158,000 may limit access for patients with ALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis. Sun, Y., Li, X., Bedlack, R.[2023]

MN-166 (ibudilast) shows promise as a neuroprotective treatment for ALS by inhibiting inflammation and glial cell activation, with early studies indicating potential improvements in survival and disease progression.

The ongoing COMBAT-ALS study, involving a randomized, double-blind, placebo-controlled design, aims to rigorously evaluate the safety, tolerability, and efficacy of MN-166 on various outcomes in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. Oskarsson, B., Maragakis, N., Bedlack, RS., et al.[2022]

In a phase 3 trial involving 174 patients with AChR-positive generalized myasthenia gravis, zilucoplan demonstrated a significant reduction in the myasthenia gravis activities of daily living (MG-ADL) score compared to placebo, indicating its efficacy as a treatment option.

Zilucoplan was generally well tolerated, with a safety profile similar to placebo, and the most common side effect was injection-site bruising, suggesting it may be a safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Howard, JF., Bresch, S., Genge, A., et al.[2023]

Zilucoplan, a C5 inhibitor, has been approved in Japan, the USA, and the EU for treating generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive and have not responded adequately to other treatments.

This medication represents a significant advancement in gMG treatment options, particularly for patients who do not respond well to steroids or immunosuppressants, and is currently under review in Australia and Canada.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zilucoplan: First Approval. Shirley, M.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. [2022]

2. England pubmed.ncbi.nlm.nih.gov

An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis. [2023]

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

Riluzole--what is its impact in our treatment and understanding of amyotrophic lateral sclerosis? [2017]

4. England pubmed.ncbi.nlm.nih.gov

MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Zilucoplan: First Approval. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome. [2020]

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

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug. [2020]

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

Amifampridine phosphate (Firdapse(®)) is effective and safe in a phase 3 clinical trial in LEMS. [2022]

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

Phosphate-mediated coanchoring of RBD immunogens and molecular adjuvants to alum potentiates humoral immunity against SARS-CoV-2. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A comparison of calcium acetate/magnesium carbonate and sevelamer-hydrochloride effects on fibroblast growth factor-23 and bone markers: post hoc evaluation from a controlled, randomized study. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Phosphate binder usage in kidney failure patients. [2022]

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

Incorporation of Phosphonate into Benzonaphthyridine Toll-like Receptor 7 Agonists for Adsorption to Aluminum Hydroxide. [2017]

15. France pubmed.ncbi.nlm.nih.gov

Binding and inhibitory activities: A novel oral therapeutic agent for the treatment of hyperphosphataemia rats. [2022]