M5049 for Lupus

Not currently recruiting at 235 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Disqualifiers: Severe infections, Psychiatric conditions, 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: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called M5049 for people with lupus, a condition where the immune system attacks healthy tissues. The trial aims to assess the long-term safety and effectiveness of M5049. Participants will receive different doses of M5049 or a placebo (a pill with no active medicine) to compare results. It is suitable for those who have completed a previous study on M5049 and have lupus affecting their skin or other parts of the body. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot participate if you received certain prohibited medications after the WILLOW study Week 24.

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

Research has shown that the treatment M5049, also known as enpatoran, has been tested in various studies for safety and effectiveness. In one study with healthy volunteers, M5049 did not cause serious side effects, indicating it was well-tolerated. Another study involving lupus patients showed positive results, including reduced disease activity.

Safety information from ongoing research suggests that M5049 is generally well-tolerated in lupus patients, even those with skin symptoms. Although the treatment remains under study, these findings offer some reassurance about its safety. Potential participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about M5049 for lupus because it targets a novel pathway in the immune system, offering a different approach from standard treatments like corticosteroids and immunosuppressants. Unlike these typical options, which broadly suppress the immune response, M5049 specifically inhibits Toll-like receptors (TLRs), which play a key role in the inflammation process associated with lupus. This targeted approach may lead to fewer side effects and potentially greater effectiveness in controlling lupus symptoms. Additionally, M5049 is being tested in various doses, allowing researchers to find the optimal balance between efficacy and safety, which is crucial for improving patient outcomes.

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

Research has shown that M5049, also known as enpatoran, may help treat lupus. Studies have found that this treatment can lower disease activity in people with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). For patients with active skin symptoms, enpatoran effectively reduced the severity of these symptoms. Taken orally, the treatment targets specific parts of the immune system, which may help manage the overactive immune response seen in lupus patients. This trial will evaluate different doses of M5049—high, medium, and low—to determine its effectiveness and safety. These findings suggest that M5049 could be a helpful option for those dealing with lupus-related skin and systemic issues. ^{2 3 4 6 7}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Are You a Good Fit for This Trial?

This trial is for people with certain types of lupus (SCLE, DLE, or SLE) who finished a previous 24-week Willow study. Participants should have a BMI between 18.5 and 35 and must not have serious infections, recent use of prohibited meds, other investigational drug studies post-Willow study Week 24, or severe health conditions that increase risk.

Inclusion Criteria

Patients with a Body Mass Index (BMI) >= 40 kilograms per meter square at Screening

Other protocol defined inclusion criteria could apply

I have completed the 24-week Willow Study for my lupus.

Exclusion Criteria

I do not have any serious ongoing infections, including COVID-19.

Patients with other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with Long Term Extension (LTE) study participation

Patients who received LTE prohibited medication during the WILLOW study or after the WILLOW study Week 24

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive M5049 at various doses to evaluate long-term safety and efficacy

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue to receive M5049 to assess long-term outcomes

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• M5049 high dose
• M5049 low dose
• M5049 medium dose
• Placebo

Trial Overview The Willow LTE Study tests the long-term safety and effectiveness of M5049 at various doses in treating lupus. It's an oral medication given to those who've completed the initial Willow study treatment period.

How Is the Trial Designed?

Group I: M5049 medium dose+ Placebo Experimental Treatment 2 Interventions

Participants with CLE (active SCLE and/or DLE) or SLE who received medium dose of M5049 in WILLOW study will continue to receive M5049 medium dose and matching placebo.

Group II: M5049 low dose + Placebo Experimental Treatment 2 Interventions

Participants with CLE (active SCLE and/or DLE) or SLE who received low dose of M5049 in WILLOW study will continue to receive M5049 low dose and matching placebo.

Group III: M5049 high dose + Placebo Experimental Treatment 2 Interventions

Participants with CLE (active SCLE and/or DLE) or SLE who received M5049 matched placebo or high dose of M5049 in WILLOW study will receive M5049 high dose .

Who Is Running the Clinical Trial?

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Lead Sponsor

Trials

60

Recruited

7,900+

Danny Bar-Zohar

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Chief Executive Officer

MD

Danny Bar-Zohar

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

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]

In a study of 1355 patients with lupus nephritis treated with tacrolimus for 5 years, the treatment was found to be well tolerated, with serious adverse drug reactions occurring mainly in the first 28 weeks and no significant increase in risk over time.

Tacrolimus significantly improved key health markers related to lupus nephritis, such as urine protein levels and anti-dsDNA antibody levels, while maintaining a low cumulative rate of progression to renal failure (6.6% at Year 5) and manageable relapse rates (30.6% at Year 5).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis: 5-year Interim Postmarketing Surveillance Study in Japan (TRUST). Takeuchi, T., Wakasugi, N., Uno, S., et al.[2021]

In the AURA-LV Phase 2 trial involving 265 participants, the addition of low-dose voclosporin to standard therapy for lupus nephritis significantly increased the rate of complete renal remission (CRR) at 24 weeks compared to placebo, with 32.6% achieving CRR versus 19.3% in the placebo group.

While voclosporin improved renal response, it was associated with a higher incidence of serious adverse events and increased mortality in the low-dose group, highlighting the need for careful monitoring when using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Rovin, BH., Solomons, N., Pendergraft, WF., et al.[2019]

A retrospective analysis of 63 matched patients suggests that a lower dose regimen of mycophenolate mofetil (MMF) and steroids may be safer and just as effective as the high dose regimen recommended by the 2012 guidelines for treating lupus nephritis.

The ongoing AURORA phase 3 study, involving 358 patients, aims to further investigate the efficacy and safety of a low dose regimen with voclosporin, MMF, and steroids, which could lead to improved long-term outcomes for lupus nephritis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of standard of care treatment with a low steroid and mycophenolate mofetil regimen for lupus nephritis in the ALMS and AURA studies. Dall'Era, M., Solomons, N., Federico, R., et al.[2019]

In a Phase IIb trial involving 305 patients with systemic lupus erythematosus (SLE), anifrolumab treatment led to a higher rate of achieving the Lupus Low Disease Activity State (LLDAS) compared to placebo, indicating its efficacy in managing SLE symptoms.

The study found that anifrolumab-treated patients not only reached LLDAS earlier but also spent more time in this state, supporting the use of LLDAS as a meaningful endpoint in SLE clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. Morand, EF., Trasieva, T., Berglind, A., et al.[2019]

In a study comparing 30 patients treated with low-moderate doses of prednisone (≤30 mg/day) to 30 patients on high doses (>30 mg/day) for lupus, both groups showed similar improvements in disease activity after one year, indicating that lower doses are just as effective.

However, patients on high doses were significantly more likely to experience glucocorticoid-related damage, with 5 patients affected compared to none in the low-dose group, highlighting the safety benefits of using lower doses of prednisone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of high versus low-medium prednisone doses for the treatment of systemic lupus erythematosus patients with high activity at diagnosis. Ruiz-Arruza, I., Barbosa, C., Ugarte, A., et al.[2018]

In a clinical trial involving 58 patients with systemic lupus erythematosus (SLE), the 50 mg weekly dose of LJP 394 resulted in the most significant reduction of serum dsDNA antibodies, with reductions of 38.1% and 37.1% at Weeks 16 and 24, respectively.

The safety profile of LJP 394 was comparable to that of the placebo, indicating that it is a well-tolerated treatment option for SLE while effectively reducing disease-related biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of systemic lupus erythematosus with LJP 394. Furie, RA., Cash, JM., Cronin, ME., et al.[2017]

A population pharmacokinetic model for mycophenolic acid (MPA) was developed using data from 19 patients with childhood-onset systemic lupus erythematosus (cSLE), revealing important insights into the drug's absorption and enterohepatic recycling processes.

The model demonstrated that MPA's pharmacokinetics can be influenced by meal timing, which is crucial for optimizing dosing strategies in patients, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of population PK model with enterohepatic circulation for mycophenolic acid in patients with childhood-onset systemic lupus erythematosus. Sherwin, CM., Sagcal-Gironella, AC., Fukuda, T., et al.[2021]

Citations

1. emdserono.com emdserono.com/us-en/company/news/press-releases/enpatoran-phase-2-data-21-05-2025.html

2025-05-21 Positive Phase 2 Data for Enpatoran The company announced positive data on enpatoran demonstrating reduction in disease activity in patients with cutaneous lupus erythematosus (CLE) and systemic ...

2. merckgroup.com merckgroup.com/en/news/enpatoran-data-eular25-12-06-2025.html

Enpatoran Phase 2 Data from Cohort B in SLE Merck showcases Phase 2 data of enpatoran for systemic lupus erythematosus, highlighting improved efficacy in patients with active skin manifestations.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04647708

NCT04647708 | Study of M5049 in CLE and SLE Participants This study is to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered M5049 in participants with systemic lupus erythematosus ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12557744/

Enpatoran, a first-in-class, selective, orally administered toll ... This study provides important tolerability data and supports the continued evaluation of enpatoran in patients with lupus, including the ongoing ...

5. jrheum.org jrheum.org/content/52/Suppl_1/11.1

RANDOMIZED, PLACEBO-CONTROLLED PHASE II ... Results 102 patients were randomized, and 100 patients were included for efficacy evaluation (placebo n = 26; enpatoran low dose n = 23; mid ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8377444/

Phase 1 study in healthy participants of the safety ... Enpatoran, previously known as M5049, is a potential first‐in‐class small molecule dual TLR antagonist having activity against both TLR7 and TLR8, which has ...

7. lupus.bmj.com lupus.bmj.com/content/11/Suppl_1/A113.2

P102 Safety evaluation from an ongoing randomized ... The objective was to evaluate safety data from the ongoing phase Ib study of enpatoran in SLE/CLE. Methods This randomized, double-blind ...