Multiple Treatments for ALS

Not currently recruiting at 85 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if several potential treatments can help people with ALS, a disease affecting nerve cells in the brain and spinal cord. Participants will receive one of several study drugs, such as ABBV-CLS-7262 (also known as Fosigotifator), or a placebo (a harmless pill with no active drug) to evaluate the treatments' effectiveness and safety. Individuals diagnosed with ALS who have experienced weakness from the disease for less than two years might be eligible. As a Phase 2/3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking ALS treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ABBV-CLS-7262 maintains a very safe track record across all studies, indicating it is well-tolerated with few serious side effects. In contrast, detailed safety information for DNL343 from past studies remains limited. The current study includes several phases, suggesting some initial safety testing has occurred, but more data is needed to fully assess its safety. In summary, while ABBV-CLS-7262 appears safe, DNL343 is still under investigation to confirm its safety for people. Participants should discuss any concerns with their healthcare providers before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ALS because they bring new approaches to tackling this challenging condition. Unlike most treatments that primarily manage symptoms, ABBV-CLS-7262 targets the underlying disease process by modulating the ISR (integrated stress response) pathway, which may help protect nerve cells from damage. CNM-Au8 introduces a groundbreaking approach by using gold nanocrystals to enhance cellular energy and reduce oxidative stress, potentially slowing disease progression. Additionally, Pridopidine, a Sigma-1 receptor agonist, may help maintain neuronal function and survival, offering a novel mechanism of action compared to traditional therapies. Each of these treatments provides a unique angle, giving researchers hope for more effective ways to combat ALS.

What evidence suggests that this trial's treatments could be effective for ALS?

Research has shown that ABBV-CLS-7262, also known as fosigotifator, is under study as a potential treatment for ALS (Amyotrophic Lateral Sclerosis) in this trial. This drug aims to reduce the harmful effects of protein misfolding, believed to contribute to ALS progression. Early studies suggest it might slow the disease by protecting nerve cells from damage. Although more research is needed to confirm its effectiveness, initial findings are promising and support further investigation. Participants in this trial may receive ABBV-CLS-7262 as part of their treatment regimen. ^{2 3 5 6 7}

Who Is on the Research Team?

Merit Cudkowicz, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04948645

NCT04948645 | A Phase 1 Study to Investigate the Safety ... Fosigotifator is an investigational drug being researched for the treatment of Amyotrophic Lateral Sclerosis. This is an up to 156-week, 2-part study. Part 1 ...

2. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M20-405

A Phase 1 Study to Investigate the Safety and ... Fosigotifator is an investigational drug being researched for the treatment of Amyotrophic Lateral Sclerosis. This is an up to 156-week, 2-part study.

3. massgeneral.org massgeneral.org/neurology/als/news/healeyamg-announces-platform-trial-update-fosigotifator

Sean M. Healey & AMG Center Announces Update in ALS ... ... ALS Platform Trial evaluating fosigotifator (ABBV-CLS-7262) in people living with amyotrophic lateral sclerosis (ALS). Fosigotifator, an ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05740813

HEALEY ALS Platform Trial - Regimen F ABBV-CLS-7262 Regimen F will evaluate the safety and efficacy of a single study drug, ABBV-CLS-7262, in participants with ALS. Detailed Description. The HEALEY ALS Platform ...

5. trial.medpath.com trial.medpath.com/drug/report/86892eab963fd37d

ABBV-CLS-7262 | Advanced Drug Monograph - MedPath Comprehensive analysis about ABBV-CLS-7262, including its mechanisms, clinical uses, and therapeutic considerations.

6. en.wikipedia.org en.wikipedia.org/wiki/Fosigotifator

Fosigotifator A formulation of fosigotifator, as its monosodium phosphate salt mixed with tromethamine, is known as ABBV-CLS-7262. Fosigotifator has been patented by AbbVie ...

7. go.drugbank.com go.drugbank.com/drugs/DB18407/clinical_trials?conditions=DBCOND0029898&phase=1&purpose=treatment&status=terminated

ABBV-CLS-7262 Terminated Phase 1 Trials for ... A Phase 1 Study to Investigate the Safety and Pharmacokinetics of Fosigotifator in Patients With Amyotrophic Lateral Sclerosis. ABBV-CLS-7262 (DB18407) ...