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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to see how well cenerimod reduces symptoms of Systemic Lupus Erythematous in adult patients with moderate to severe symptoms. The main questions it aims to answer are: * How well cenerimod works on top of the treatment already being administered. * How safe cenerimod is for adult patients with Systemic Lupus Erythematosus. Researchers will compare one dose of cenerimod and a placebo to see how well cenerimod works when it is added to the treatment already being administered. In this research study approximately 210 participants will receive cenerimod and approximately 210 participants will receive placebo for 12 months.

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.

What data supports the effectiveness of the drug Cenerimod for treating systemic lupus erythematosus?

Cenerimod is a drug being studied for systemic lupus erythematosus (SLE) and has shown similar effects in reducing lymphocyte counts (a type of white blood cell) in both white and Asian subjects, which is a promising sign for its effectiveness. Additionally, it was well-tolerated in healthy subjects, suggesting it could be a safe option for SLE patients. ^{1 2 3 4 5}

Is Cenerimod safe for humans?

Cenerimod has been tested in healthy subjects and was found to be safe and well-tolerated, with only one minor adverse event (eye irritation) that was not linked to the drug. It caused a temporary decrease in heart rate, which is common with similar drugs, but no serious side effects were reported. ^{1 2 3 6 7}

How is the drug cenerimod unique for treating systemic lupus erythematosus?

Cenerimod is unique because it is a selective sphingosine-1-phosphate 1 receptor modulator, which means it works by specifically targeting and modulating a receptor involved in immune cell movement, potentially reducing inflammation in systemic lupus erythematosus. This mechanism is different from many traditional treatments that often broadly suppress the immune system. ^{1 2 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Idorsia Pharmaceuticals Ltd.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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 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]

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]

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]

References

1. United States 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. [2022]

2. England 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. [2022]

3. England 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. [2019]

4. United States 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. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

SLEDAI-2K Does Not Conceal Worsening in a Particular System When There Is Overall Improvement. [2015]

6. Portugal pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Absorption, distribution, metabolism, and excretion of cenerimod, a selective S1P1 receptor modulator in healthy subjects. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Modelling pharmacokinetics and pharmacodynamics of the selective S1P1 receptor modulator cenerimod in healthy subjects and systemic lupus erythematosus patients. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive. [2022]