Cenerimod for Systemic Lupus Erythematosus

(OPUS OLE Trial)

Enrolling by invitation at 63 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety and effectiveness of cenerimod for individuals with moderate to severe systemic lupus erythematosus (SLE), an autoimmune disease that can cause joint pain, fatigue, and skin rashes. The trial will assess whether cenerimod causes any side effects when used alongside other lupus treatments and how effectively it reduces lupus symptoms over one to three years. Individuals who have completed a previous study with cenerimod or a placebo and have moderate to severe lupus symptoms might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to help bring a new treatment closer to availability.

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.

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

Research has shown that cenerimod is generally safe for people with systemic lupus erythematosus. In earlier studies, patients taking cenerimod did not experience more serious side effects than those taking a placebo (a harmless pill with no active medicine). These studies also found that patients on cenerimod had improved mental and physical health scores. This suggests the treatment is safe for long-term use. However, like any medication, some side effects might occur, so staying informed and discussing any concerns with a doctor is important. ^{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 (S1P) receptor, which plays a key role in immune cell trafficking. Unlike standard treatments for systemic lupus erythematosus (SLE), such as corticosteroids and immunosuppressants, which broadly dampen the immune system, Cenerimod offers a more targeted approach. This specificity could potentially reduce the risk of side effects associated with traditional therapies. Researchers are excited about Cenerimod because of its potential to provide a more precise and safer way to manage SLE by directly modulating immune cell movement.

What evidence suggests that cenerimod might be an effective treatment for systemic lupus erythematosus?

Research has shown that cenerimod can help reduce symptoms of systemic lupus erythematosus (SLE). In one study, patients taking 4 mg of cenerimod showed noticeable improvements in both mental and physical health compared to those taking a placebo. Another study found that the same dose led to ongoing improvements in SLE symptoms from the study's start. Although one study did not fully achieve its main goal, it still demonstrated a clear decrease in disease activity. These results suggest that cenerimod may help manage SLE symptoms when used alongside current treatments. ^{2 4 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Viatris Innovation GmbH

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Viatris Innovation GmbH

Lead Sponsor

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

Citations

1. 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).

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

Cenerimod, a sphingosine-1-phosphate receptor ... We aimed to determine the efficacy, safety, and tolerability of four doses of cenerimod in adults with moderate-to-severe SLE receiving ...

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

RESULTS FROM THE PHASE 2 CARE STUDY 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. newsroom.viatris.com newsroom.viatris.com/2024-12-18-Viatris-Announces-Publication-of-Phase-2b-CARE-Study-Data-for-Cenerimod-in-Lancet-Rheumatology

Viatris Announces Publication of Phase 2b CARE Study ... Cenerimod 4 mg demonstrated clinically meaningful and sustained improvement from baseline on multiple measures of SLE disease activity compared to placebo.

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/NCT02472795

NCT02472795 | Clinical Study to Investigate the Biological ... International trial to evaluate the biological activity and safety of cenerimod (ACT-334441) in systemic lupus erythematosus (SLE) patients. Detailed ...

7. 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 ...