ESK-001 for Lupus

(LUMUS Trial)

Not currently recruiting at 205 trial locations

Overseen By Central Recruiting

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alumis Inc

Must be taking: Corticosteroids, Antimalarials, DMARDS

Disqualifiers: Drug-induced SLE, Lupus nephritis, Neuropsychiatric SLE, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ESK-001 for individuals with lupus, a condition where the immune system attacks healthy tissues. The goal is to assess the safety and effectiveness of different doses of ESK-001 compared to a placebo (a non-active pill). Participants must have lived with lupus for at least 6 months and be experiencing active symptoms, possibly while on stable doses of specific medications like corticosteroids or antimalarials. The study aims to determine if ESK-001 can improve the quality of life for those with lupus. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important lupus research.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of certain medications, like oral corticosteroids, antimalarials, or specific DMARDs (disease-modifying antirheumatic drugs), before and during the study. You should not increase the dose of these medications between screening and the start of the trial.

Is there any evidence suggesting that ESK-001 is likely to be safe for humans?

Research has shown that ESK-001 is generally safe and well-tolerated. In studies with healthy participants, ESK-001 demonstrated good safety results. Participants did not experience significant side effects, and the drug was well-tolerated at various dose levels, indicating minimal or mild negative reactions.

The treatment targets a specific pathway in the body and has been tested at different doses without major issues. These findings suggest ESK-001 is likely safe for those considering joining a clinical trial for lupus. ^{1 2 3 4 5}

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

Researchers are excited about ESK-001 for lupus because it introduces a novel approach with its unique oral tablet form targeting specific pathways in the immune system. Unlike standard treatments like corticosteroids or immunosuppressants, which can have broad, sometimes harsh effects on the body's immune response, ESK-001 aims to more precisely modulate the immune system. This precision could potentially lead to fewer side effects and improved efficacy in managing lupus symptoms. The different dose levels being tested also provide flexibility in optimizing treatment for patients with varying needs.

What evidence suggests that ESK-001 might be an effective treatment for lupus?

Research shows that ESK-001 may help treat Systemic Lupus Erythematosus (SLE). Studies have found that ESK-001 can lower certain substances in the body that indicate disease. In this trial, participants will receive different doses of ESK-001 or a placebo. Patients who took ESK-001 at a specific dose saw their symptoms remain stable or improve over time. The chance of drugs like ESK-001 getting approved is about 39%, which is encouraging. These results suggest that ESK-001 could help manage symptoms in people with SLE. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults with active Systemic Lupus Erythematosus (SLE) for at least 6 months, meeting specific disease criteria and on stable medications like Azathioprine or Methotrexate. Excluded are those with chronic infections, other autoimmune diseases that could affect results, recent use of oral anti-infectives, severe unrelated conditions, or a history of significant neuropsychiatric SLE.

Inclusion Criteria

I've been on a stable dose of corticosteroids (≤40 mg/day) for at least 2 weeks.

I have had lupus for over 6 months, with active symptoms and positive tests.

I take 200 mg or less of Azathioprine daily.

Exclusion Criteria

I have had a severe herpes infection before.

I haven't had a serious infection except for nail fungus in the last 8 weeks.

I haven't been hospitalized or needed IV antibiotics for an infection in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment

Participants receive ESK-001 or placebo for 48 weeks to assess efficacy, safety, and pharmacokinetics

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• ESK-001
• Placebo

Trial Overview

The trial is testing the effectiveness and safety of multiple doses of a new drug called ESK-001 against a placebo in adults with SLE. It will compare how well each treatment works and monitor any changes in the disease's activity and severity.

How Is the Trial Designed?

Group I: ESK-001 Dose Level 3 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Group II: ESK-001 Dose Level 2 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Group III: ESK-001 Dose Level 1 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Group IV: Placebo Placebo Group 1 Intervention

Placebo administered as an oral tablet

Who Is Running the Clinical Trial?

Alumis Inc

Lead Sponsor

Trials

9

Recruited

4,200+

Published Research Related to This Trial

In a 36-week phase IIb trial involving 185 adults with active systemic lupus erythematosus, the immunotherapeutic vaccine interferon-α kinoid (IFN-K) successfully induced neutralising antibodies in 91% of patients and significantly reduced the interferon gene signature, indicating its potential efficacy.

While the primary clinical endpoint was not met, IFN-K showed significant benefits in secondary outcomes, including a higher rate of achieving lupus low disease activity state (53% vs 30%) and a notable reduction in corticosteroid use, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study. Houssiau, FA., Thanou, A., Mazur, M., et al.[2021]

In a phase 3 study involving 516 patients with active systemic lupus erythematosus (SLE), ustekinumab did not show superior efficacy compared to placebo, with similar response rates at week 52 (44% for ustekinumab vs. 56% for placebo).

The study was discontinued due to lack of efficacy, but there were no safety concerns, and the adverse events reported were consistent with ustekinumab's known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus. van Vollenhoven, RF., Kalunian, KC., Dörner, T., et al.[2022]

The JAK1 inhibitor GSK2586184 was evaluated in a study involving 50 adults with systemic lupus erythematosus (SLE) over 12 weeks, but it showed no significant effect on interferon transcriptional biomarkers, leading to the study being declared futile.

Safety concerns arose during the trial, including elevated liver enzymes in six patients, which resulted in immediate cessation of dosing and indicated that GSK2586184 is not suitable for further evaluation in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. Kahl, L., Patel, J., Layton, M., et al.[2017]

Belimumab was found to be more effective than placebo in treating systemic lupus erythematosus (SLE), showing improvements in various disease activity measures, while rituximab did not demonstrate superior efficacy over placebo.

Both belimumab and rituximab exhibited satisfactory safety profiles, with no significant differences in adverse events compared to placebo, suggesting that biologic agents are promising options for SLE treatment and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis. Borba, HH., Wiens, A., de Souza, TT., et al.[2022]

In a study of 38 Portuguese patients with Systemic Lupus Erythematosus (SLE), belimumab demonstrated significant effectiveness, with SLE Responder Index (SRI) response rates increasing from 51.9% at 6 months to 91.7% at 24 months, indicating a reduction in disease activity.

Belimumab was associated with a good safety profile, with only five patients experiencing adverse events, primarily infections, and the treatment led to a significant decrease in disease activity markers and daily steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab in the treatment of Portuguese Systemic Lupus Erythematosus patients: a real-life multicenter study. Fernandes, BM., Barreira, S., Fonseca, JE., et al.[2021]

Citations

1.

investors.alumis.com

investors.alumis.com/news-releases/news-release-details/alumis-presents-data-highlighting-esk-001s-potential-high?mobile=1&mobile=1

Alumis Presents Data Highlighting ESK-001's Potential as a ...

“The ACR data show that treatment with ESK-001 downregulates key cytokines and disease biomarkers of SLE,” said Dr. Jörn Drappa, Alumis' Chief ...

2.

clinicaltrials.eu

clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-esk-001-for-adults-with-systemic-lupus-erythematosus/

Study on the Safety and Effectiveness of ESK-001 for ...

This study assesses the safety and effectiveness of the medication ESK-001 in treating adult patients with Systemic Lupus Erythematosus, ...

3.

investors.alumis.com

investors.alumis.com/news-releases/news-release-details/late-breaking-esk-001-phase-2-ole-data-presented-2025-aad-annual?mobile=1&mobile=1

Late-Breaking ESK-001 Phase 2 OLE Data Presented at 2025 ...

These data demonstrated that patients receiving 40 mg twice daily dosing of ESK-001 achieved long-term sustained or increasing clinical responses through Week ...

4.

pharmaceutical-technology.com

pharmaceutical-technology.com/data-insights/esk-001-alumis-systemic-lupus-erythematosus-likelihood-of-approval/

ESK-001 by Alumis for Systemic Lupus Erythematosus

According to GlobalData, Phase II drugs for Systemic Lupus Erythematosus have a 39% phase transition success rate (PTSR) indication benchmark ...

5.

ctv.veeva.com

ctv.veeva.com/study/phase-2-placebo-controlled-study-to-assess-the-safety-and-efficacy-of-esk-001-in-active-systemic-lup

Phase 2 Placebo-Controlled Study to Assess the Safety and ...

The purpose of this study is to assess the clinical efficacy, safety, PK, and PD of multiple dose levels of ESK-001 compared with placebo in ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11602527/

Safety, tolerability, pharmacokinetics, and ...

ESK‐001 was generally safe and well‐tolerated in healthy participants, showed linear dose‐dependent PK characteristics, and maximally inhibited TYK2‐dependent ...

7.

hra.nhs.uk

hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/safety-efficacy-and-pharmacokinetics-dose-levels-of-esk-001-in-adult-patient-with-lupus/

Safety, Efficacy, and Pharmacokinetics Dose Levels of ESK ...

The primary goal of this study is to assess the clinical efficacy, safety, PK, and PD of multiple dose levels of ESK-001 compared with placebo in adult ...