Enpatoran for Lupus

Recruiting at 173 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: EMD Serono Research & Development Institute, Inc.

Must be taking: Immunomodulators, Corticosteroids

Disqualifiers: Autoimmune diseases, Uncontrolled conditions, Infections, others

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

456 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an oral medication called Enpatoran on patients with different types of lupus. It aims to find out if the drug is safe and effective in reducing lupus symptoms.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of at least one standard lupus treatment, such as immunosuppressants or corticosteroids, so you may not need to stop your current medications if they are part of these treatments.

Is Enpatoran safe for humans?

Enpatoran has been tested in a phase I study with healthy participants, where different doses were evaluated for safety. The study involved doses up to 200 mg daily for 14 days, and the data from this study was used to inform dose selection for further trials, suggesting it has been considered safe enough to proceed with additional research. ^{1 2 3 4 5}

Research Team

Medical Responsible

Principal Investigator

EMD Serono Research & Development Institute, Inc.

Eligibility Criteria

The WILLOW study is for people with systemic or cutaneous lupus who are on a stable dose of standard lupus treatments. Participants should have active skin symptoms scored at least 8 on the CLASI-A scale, and may also have certain levels of overall disease activity as measured by BILAG 2004 and SELENA-SLEDAI scores.

Inclusion Criteria

I have active lupus with specific skin and organ involvement.

My skin condition due to lupus is active and severe.

Other protocol defined inclusion criteria could apply

Exclusion Criteria

I do not have uncontrolled heart issues, lupus affecting my kidneys, or active brain disorders.

I have had cancer before.

I do not have uncontrolled seizures or other serious brain problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orally administered Enpatoran or placebo over 24 weeks in a randomized, double-blind, placebo-controlled setting

24 weeks

Visits every 2 or 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-7 weeks

Treatment Details

Interventions

• Enpatoran
• M5049
• Placebo

Trial Overview This study tests different doses of Enpatoran, an oral medication, against a placebo over 24 weeks to see how well it works and how safe it is for treating lupus. The trial randomly assigns participants to receive either low, medium, high doses of Enpatoran or a placebo in a double-blind setting.

Participant Groups

Group I: Cohort B (Part 2): Enpatoran medium dose Experimental Treatment 1 Intervention

Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive medium dose of Enpatoran.

Group II: Cohort B (Part 2): Enpatoran low dose Experimental Treatment 1 Intervention

Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive low dose of M5049.

Group III: Cohort B (Part 1 + Part 2): Enpatoran high dose Experimental Treatment 1 Intervention

Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive high dose of Enpatoran.

Group IV: Cohort A: Enpatoran medium dose Experimental Treatment 1 Intervention

Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive medium dose of Enpatoran.

Group V: Cohort A: Enpatoran low dose Experimental Treatment 1 Intervention

Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive low dose of Enpatoran.

Group VI: Cohort A: Enpatoran high dose Experimental Treatment 1 Intervention

Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive high dose of Enpatoran.

Group VII: Cohort A: Placebo Placebo Group 1 Intervention

Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (Cutaneous Lupus Erythematosus Disease Area and Severity Index \[CLASI-A\] greater than or equal to \[\>=\] 8) will be enrolled in Cohort A to receive placebo matched to Enpatoran.

Group VIII: Cohort B (Part 1 + Part 2): Placebo Placebo Group 1 Intervention

Participants with active SLE who have moderate to high systemic disease activity (British Isles Lupus Assessment Group \[BILAG A/2B\]) with 1 or 2 of the following: CLASI-A \>= 8 and/or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) \>= 6 will be enrolled in Cohort B to receive placebo matched to Enpatoran .

Who Is Running the Clinical Trial?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Findings from Research

SM934, an artemisinin derivative, effectively reduced autoimmune symptoms in lupus-prone MRL/lpr mice by inhibiting the production of inflammatory cytokines IFNγ and IL-17, which are crucial for lupus development.

In vivo treatment with SM934 led to significant improvements in kidney function and overall survival, demonstrating its potential as a therapeutic option for autoimmune diseases by promoting Treg cell development and suppressing harmful Th1 and Th17 responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses. Hou, LF., He, SJ., Li, X., et al.[2011]

Enpatoran, a dual TLR 7 and TLR 8 inhibitor, has shown promise in treating lupus and COVID-19 pneumonia, with a phase I study involving 72 healthy participants informing its pharmacokinetics and pharmacodynamics.

Model simulations suggest that dosing regimens of 25, 50, and 100 mg twice daily can effectively inhibit cytokine secretion, with 100 mg b.i.d. providing nearly complete target coverage for 24 hours, while 50 mg b.i.d. may be optimal for COVID-19 to minimize interference with antiviral responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need. Klopp-Schulze, L., Shaw, JV., Dong, JQ., et al.[2022]

A bispecific antagonist targeting both PTGDR-1 and PTGDR-2, AMG853, effectively reduced symptoms of lupus-like nephritis in mice by dampening basophil activation and decreasing harmful autoantibody production.

Treatment with AMG853 for 10 days led to significant improvements, including reduced levels of dsDNA-specific IgG and decreased renal inflammation, suggesting its potential as a therapeutic option for systemic lupus erythematosus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG853, A Bispecific Prostaglandin D2 Receptor 1 and 2 Antagonist, Dampens Basophil Activation and Related Lupus-Like Nephritis Activity in Lyn-Deficient Mice. Pellefigues, C., Tchen, J., Saji, C., et al.[2022]

In a phase II trial involving 37 patients with discoid lupus erythematosus (DLE), R-salbutamol cream 0.5% showed significant improvements in symptoms such as scaling, pain, and itching compared to a placebo, indicating its efficacy as a treatment.

The cream was found to be safe and well-tolerated, with no serious adverse events reported, suggesting it could be a promising new topical therapy for patients with therapy-resistant DLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus. Jemec, GB., Ullman, S., Goodfield, M., et al.[2013]

LJP-394 (abetimus sodium) is an investigational drug designed to lower anti-dsDNA antibody levels and may help prevent kidney flares in patients with systemic lupus erythematosus (SLE), based on data from 13 clinical trials involving over 800 patients over 10 years.

If ongoing trials confirm its efficacy, LJP-394 could potentially replace or reduce the dosage of current immunosuppressive treatments, which are effective but carry significant short- and long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LJP-394 (abetimus sodium) in the treatment of systemic lupus erythematosus. Mosca, M., Baldini, C., Bombardieri, S.[2019]

References

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

Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses. [2011]

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

Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need. [2022]

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

AMG853, A Bispecific Prostaglandin D2 Receptor 1 and 2 Antagonist, Dampens Basophil Activation and Related Lupus-Like Nephritis Activity in Lyn-Deficient Mice. [2022]

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

A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus. [2013]

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

LJP-394 (abetimus sodium) in the treatment of systemic lupus erythematosus. [2019]