ESK-001 for Lupus

(LUMUS Trial)

Recruiting at 173 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

388 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called ESK-001 to see if it can help adults with SLE, a chronic autoimmune disease. The study will check the effectiveness and safety of ESK-001 over several months.

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.

What safety data exists for ESK-001 or similar treatments in humans?

The study on a similar treatment, GSK2586184, for lupus found safety concerns, including elevated liver enzymes and a serious drug reaction in some patients, leading to the study's early termination. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

1. England 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. [2022]

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

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. [2017]

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

Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis. [2022]

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

IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study. [2021]

5. Portugal pubmed.ncbi.nlm.nih.gov

Belimumab in the treatment of Portuguese Systemic Lupus Erythematosus patients: a real-life multicenter study. [2021]