Cenerimod for Systemic Lupus Erythematosus

(OPUS OLE Trial)

Recruiting at 41 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Idorsia Pharmaceuticals Ltd.

Must be taking: Lupus medications

Disqualifiers: Renal disease, CNS lupus, tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 12-36 months

680 Participants Needed

Trial Summary

What is the purpose of this trial?

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 systemic lupus erythematosus. The main questions it aims to answer are: * Whether cenerimod causes any adverse effects ('side effects') when given on top of drugs already being given for systemic lupus erythematosus. * How well cenerimod works to reduce symptoms of systemic lupus erythematosus when taken for at least 1 year and up to 3 years. Participants taking part in this study will have already taken part in another study, where they received either cenerimod or placebo (look-alike substance containing no active drug) for 1 year. In this clinical study approximately 680 participants will receive cenerimod (on top of drugs already being given for systemic lupus erythematosus) for at least 1 year and up to 3 years.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications for systemic lupus erythematosus. Cenerimod will be given on top of the drugs you are already taking for your condition.

What data supports the effectiveness of the drug Cenerimod for treating Systemic Lupus Erythematosus?

Cenerimod, a drug similar to other S1P1 receptor modulators like amiselimod, has been studied for its safety and effects in patients with SLE, showing potential as a treatment option. While specific effectiveness data for Cenerimod in SLE is not detailed, similar drugs have shown promise in reducing disease activity. ^{1 2 3 4 5}

Is Cenerimod safe for humans?

Cenerimod has been tested in healthy subjects and patients with systemic lupus erythematosus, showing it is generally safe and well-tolerated. Some subjects experienced a temporary drop in heart rate, but no serious side effects were linked to the drug. ^{2 3 6 7 8}

What makes 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 specifically targets and modulates a receptor involved in immune cell movement, potentially reducing inflammation in systemic lupus erythematosus. This mechanism is different from other treatments that may not target this specific pathway. ^{2 3 6 9 10}

Research Team

Clinical Trials

Principal Investigator

Idorsia Pharmaceuticals Ltd.

Eligibility Criteria

This trial is for adults with moderate to severe systemic lupus erythematosus who have already participated in a previous study involving cenerimod or placebo. They should be stable on their current lupus medications.

Inclusion Criteria

Signed and dated informed consent form prior to any study-mandated procedure

I have lupus and finished a 12-month treatment in a specific study.

Participants with a diagnosis of systemic lupus erythematosus who completed the last scheduled visit of the parent study. Participants who did not complete the last scheduled visit for reasons beyond their control may be eligible for this study upon approval by the sponsor

Exclusion Criteria

I have been diagnosed with active or latent tuberculosis.

I have severe lupus affecting my kidneys, brain, or causing serious mental health issues.

Judged not eligible to participate by the investigator, for any other reason

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cenerimod 4 mg daily for at least 1 year and up to 3 years, in addition to background therapy for systemic lupus erythematosus

12-36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cenerimod

Trial Overview The study tests the long-term safety and effectiveness of cenerimod, an additional treatment given alongside standard lupus drugs. Participants will take cenerimod for at least one year, possibly extending to three years.

Participant Groups

Group I: Cenerimod 4 mg Experimental Treatment 1 Intervention

Participants will receive oral cenerimod once daily in addition to background systemic lupus erythematosus therapy, for at least 1 year and up to a maximum of 3 years.

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

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]

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]

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]

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]

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]

Belimumab, administered at doses of 1, 4, and 10 mg/kg, was generally well tolerated in patients with systemic lupus erythematosus (SLE), showing similar rates of adverse events compared to placebo across three clinical trials.

The rates of serious adverse events and serious infections were comparable between belimumab and placebo, suggesting that belimumab does not significantly increase the risk of severe side effects when used alongside standard SLE therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Wallace, DJ., Navarra, S., Petri, MA., et al.[2022]

In a phase 2b study involving 308 adults with systemic lupus erythematosus (SLE), iberdomide significantly reduced B cells and plasmacytoid dendritic cells while increasing regulatory T cells (Tregs) and interleukin 2 (IL-2), indicating its potential to rebalance immune abnormalities in SLE.

Iberdomide demonstrated a strong clinical efficacy in patients with high type I interferon (IFN) expression, significantly decreasing the type I IFN gene signature by 81.5%, which correlates with its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological impact of iberdomide in patients with active systemic lupus erythematosus. Lipsky, PE., Vollenhoven, RV., Dörner, T., et al.[2022]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

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

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. 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]

4. Germany pubmed.ncbi.nlm.nih.gov

Belimumab for the treatment of corticosteroid-dependent systemic lupus erythematosus: from clinical trials to real-life experience after 1 year of use in 48 Brazilian patients. [2018]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Portugal pubmed.ncbi.nlm.nih.gov

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

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

Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. [2022]

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

Biological impact of iberdomide in patients with active systemic lupus erythematosus. [2022]

10. 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]