Cenerimod for Systemic Lupus Erythematosus

(OPUS-2 Trial)

Recruiting at 112 trial locations

Overseen By Idorsia Clinical Trial Information Europe

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Idorsia Pharmaceuticals Ltd.

Must be taking: Antimalarials, Mycophenolate, Azathioprine, Methotrexate

Must not be taking: Beta-blockers, QT-prolonging drugs, Cyclophosphamide, others

Disqualifiers: Pregnancy, CNS lupus, Heart disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called cenerimod to determine if it can reduce symptoms in adults with moderate to severe Systemic Lupus Erythematosus (SLE), a condition where the immune system attacks the body. Researchers aim to assess how well cenerimod works when added to current SLE treatments and its safety. Participants will receive either cenerimod or a placebo (a harmless pill with no active ingredient) for 12 months. The trial seeks adults diagnosed with SLE for at least 6 months who currently experience symptoms like joint pain, rashes, or mouth ulcers. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications for Systemic Lupus Erythematosus, as it tests cenerimod on top of existing treatments. However, certain medications must be stable for a period before joining, and some other medications are not allowed close to the trial start.

Is there any evidence suggesting that cenerimod is likely to be safe for humans?

Research shows that cenerimod is generally safe. In earlier studies, cenerimod was tested on people with systemic lupus erythematosus (SLE) and was usually well-tolerated. Some reports noted improvements in patients' mental and physical health over time, suggesting it might be safe for long-term use.

One study specifically examined the safety and tolerability of cenerimod for adults with SLE. The results showed that patients did not experience severe side effects, indicating that cenerimod could be safe for those with moderate to severe lupus symptoms.

For those considering joining a clinical trial for cenerimod, these findings offer reassurance about its safety based on past research. ^{1 2 3 4 5}

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

Cenerimod is unique because it targets the sphingosine-1-phosphate receptor 1 (S1P1), which plays a crucial role in regulating immune cell movement. Unlike traditional treatments for systemic lupus erythematosus (SLE) that often focus on suppressing the immune system broadly, Cenerimod offers a more targeted approach, potentially reducing specific inflammatory responses without widespread immune suppression. This targeted action could lead to fewer side effects and improved quality of life for patients. Researchers are excited about Cenerimod because it represents a novel mechanism that might offer a more precise treatment option for SLE, with the hope of achieving better outcomes.

What evidence suggests that cenerimod might be an effective treatment for Systemic Lupus Erythematosus?

Research has shown that cenerimod, a type of medication, may help treat systemic lupus erythematosus (SLE). In this trial, participants will receive either 4 mg of cenerimod or a placebo once daily, alongside their existing SLE therapy. Earlier studies found that patients taking 4 mg of cenerimod experienced significant improvements in quality of life compared to those on a placebo. Specifically, both mental and physical health improved after six months. Although one study did not fully achieve its main goal after data adjustments, a noticeable decrease in SLE symptoms occurred with cenerimod 4 mg. These results suggest that cenerimod could help reduce symptoms in people with SLE. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Idorsia Pharmaceuticals Ltd.

Are You a Good Fit for This Trial?

Adults with moderate to severe Systemic Lupus Erythematosus (SLE) who have been on stable SLE medications for at least a month can join. They must not be pregnant, planning pregnancy, or breastfeeding and agree to regular pregnancy tests and effective contraception if applicable. Excluded are those with certain heart conditions, liver diseases, recent use of specific drugs like rituximab or anifrolumab, severe respiratory issues, cancer history (with exceptions), or major organ involvement by SLE.

Inclusion Criteria

Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 Visual Analogue Scale (VAS)

Signed Informed Consent Form (ICF) prior to any study-mandated procedure

For women of childbearing potential (WoCBP): Negative serum pregnancy test at Screening, agreement to undertake monthly urine pregnancy tests, agreement to use a highly effective method of contraception

Exclusion Criteria

My lupus affects my brain or nerves severely.

Pregnant, planning to become pregnant up to Final Study Visit or lactating women

I have swelling in my retina or active eye inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cenerimod or placebo once daily in addition to background SLE therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cenerimod
• Placebo

Trial Overview The trial is testing the effectiveness and safety of Cenerimod compared to a placebo in reducing SLE symptoms over 12 months. Participants will continue their current treatments while adding either Cenerimod or a placebo. The study aims to enroll around 420 participants split evenly between the two groups.

How Is the Trial Designed?

Group I: Cenerimod 4 mg Experimental Treatment 1 Intervention

Participants will receive cenerimod once daily in addition to background SLE therapy.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo once daily in addition to background SLE therapy.

Who Is Running the Clinical Trial?

Idorsia Pharmaceuticals Ltd.

Lead Sponsor

Trials

124

Recruited

36,400+

Antonio Olivieri

Idorsia Pharmaceuticals Ltd.

Chief Medical Officer since 2024

Not specified

André C. Muller

Idorsia Pharmaceuticals Ltd.

Chief Executive Officer

Not specified

Published Research Related to This Trial

Cenerimod, a selective sphingosine 1-phosphate 1 receptor modulator, demonstrated a significant dose-dependent reduction in total lymphocyte count and improved SLE Disease Activity Index scores in patients with systemic lupus erythematosus (SLE) over 12 weeks, indicating its potential efficacy as a treatment.

The study showed that cenerimod had an acceptable safety profile, with similar rates of treatment-emergent adverse events across all doses compared to placebo, and only a minor, temporary decrease in heart rate observed shortly after dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study. Hermann, V., Batalov, A., Smakotina, S., et al.[2022]

Amiselimod, an oral medication for systemic lupus erythematosus (SLE), was generally well tolerated in a phase Ib trial with 17 participants, showing no serious adverse events or significant cardiac effects.

The treatment led to a decrease in anti-double stranded-DNA antibodies and improved SLE disease activity in some patients, suggesting potential efficacy, although low lymphocyte counts were noted as a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study. Tanaka, Y., Kondo, K., Ichibori, A., et al.[2021]

Cenerimod, a medication being developed for systemic lupus erythematosus, does not significantly affect the pharmacokinetics of the combined oral contraceptive (COC), allowing for safe use during treatment.

In a study with 24 healthy participants, while exposure to levonorgestrel increased slightly (10-25%) with cenerimod, the overall safety profile was good, with only minor adverse events reported, indicating that COC can be safely used alongside cenerimod.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive. Juif, PE., Mueller, MS., Charfi, H., et al.[2022]

Cenerimod, a drug being developed for systemic lupus erythematosus, showed similar pharmacokinetics and pharmacodynamics in both white and Asian subjects, indicating that the same dosage can be used for both ethnic groups in future studies.

The drug was found to be safe and well-tolerated, with only one minor adverse event reported, suggesting a favorable safety profile for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Cenerimod, A Selective S1P1 R Modulator, Are Not Affected by Ethnicity in Healthy Asian and White Subjects. Juif, PE., Dingemanse, J., Winkle, P., 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]

Cenerimod, a potential treatment for systemic lupus erythematosus, showed a total mean cumulative recovery of 84% after a single oral dose, primarily excreted in feces (58-100%) with minimal amounts in urine (4.6-12%).

The study identified a significant metabolite, M32, which accounted for 23% of radioactivity in urine and 66% in feces, indicating that while cenerimod itself was primarily excreted in feces, M32 is a key metabolite that may play a role in its pharmacological profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, distribution, metabolism, and excretion of cenerimod, a selective S1P1 receptor modulator in healthy subjects. Boof, ML., van Lier, JJ., English, S., et al.[2020]

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]

Cenerimod, a selective sphingosine-1-phosphate 1 receptor modulator, reaches steady state in approximately 49 days of treatment, with minimal changes in drug exposure after 35 days, indicating a stable pharmacokinetic profile for long-term use.

The incidence of low lymphocyte counts is predicted to be higher in systemic lupus erythematosus (SLE) patients (25.9% for counts below 0.5 × 10^9 cells/L) compared to healthy subjects (18.2%), suggesting a need for monitoring in this population, although dose individualization is not deemed necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modelling pharmacokinetics and pharmacodynamics of the selective S1P1 receptor modulator cenerimod in healthy subjects and systemic lupus erythematosus patients. Lott, D., Juif, PE., Dingemanse, J., et al.[2021]

In a phase III trial with 819 patients, belimumab at 10 mg/kg significantly improved the SLE Responder Index response rate at week 52 compared to placebo (43.2% vs. 33.5%), indicating its efficacy in reducing disease activity in systemic lupus erythematosus (SLE).

Belimumab was generally well tolerated, with serious adverse events being comparable across treatment groups, suggesting that it is a safe addition to standard therapy for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Furie, R., Petri, M., Zamani, O., et al.[2022]

In a study of 158 patients with systemic lupus erythematosus, the SLEDAI-2K effectively identified 109 patients who showed overall improvement in disease activity without significant worsening in other areas.

Among the improved patients, only 11 had new laboratory descriptors that were not clinically significant, indicating that the SLEDAI-2K is reliable for assessing true improvements in disease status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLEDAI-2K Does Not Conceal Worsening in a Particular System When There Is Overall Improvement. Touma, Z., Gladman, DD., Su, J., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39586304/

Cenerimod, a sphingosine-1-phosphate receptor ... Cenerimod is a selective S1P 1 receptor modulator under investigation for the treatment of systemic lupus erythematosus (SLE).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03742037

Study Details | NCT03742037 | Efficacy and Safety of Four ... The purpose of the study is to assess the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with systemic lupus erythematosus (SLE).

3. jrheum.org jrheum.org/content/52/Suppl_1/183.1

EFFECT OF CENERIMOD ON QUALITY OF LIFE IN ... Patients with cenerimod 4 mg groups showed meaning full improvements in the mental and physical components of the SF-36v2 scores compared to placebo at month 6.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02472795

NCT02472795 | Clinical Study to Investigate the Biological ... The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2665991324002467

Cenerimod, a sphingosine-1-phosphate receptor ... Although the primary endpoint was not met after adjustment for multiplicity, treatment with cenerimod 4·0 mg resulted in reduction in SLE disease activity.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06475742

Long-term Safety and Tolerability of Cenerimod in Adults ... The goal of this clinical study is to learn about the long-term safety and tolerability of cenerimod in adult patients with moderate to severe symptoms of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6861098/

First use of cenerimod, a selective S1P1 receptor modulator ... With an acceptable safety profile, the efficacy findings suggest that cenerimod has the potential to treat patients with SLE.