A Research Study to Evaluate the Efficacy and Safety of Cenerimod in Subjects Suffering From Systemic Lupus Erythematosus (OPUS-2)
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| ClinicalTrials.gov Identifier: NCT05672576 |
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Recruitment Status :
Recruiting
First Posted : January 5, 2023
Last Update Posted : April 24, 2024
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Sponsor:
Idorsia Pharmaceuticals Ltd.
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lupus Erythematosus, Systemic | Drug: Cenerimod Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 420 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of Cenerimod in Adult Subjects With Moderate-to-severe Systemic Lupus Erythematosus (SLE) on Top of Background Therapy |
| Actual Study Start Date : | June 26, 2023 |
| Estimated Primary Completion Date : | October 31, 2026 |
| Estimated Study Completion Date : | May 1, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Systemic lupus erythematosus
MedlinePlus related topics:
Lupus
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cenerimod 4 mg
Participants will receive cenerimod once daily in addition to background SLE therapy.
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Drug: Cenerimod
Cenerimod will be supplied as film-coated tablets at the dose of 4 mg.
Other Name: ACT-334441 |
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Placebo Comparator: Placebo
Participants will receive matching placebo once daily in addition to background SLE therapy.
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Drug: Placebo
Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod. |
Primary Outcome Measures :
- Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 12 compared to baseline [ Time Frame: At Month 12 compared to Day 1 (pre-dose baseline) ]
Response on SRI-4 is defined as:
- Reduction from baseline of at least 4 points in the modified Systemic Lupus Erythematosus Disease Activity Index-2000 score (mSLEDAI-2K [SLEDAI-2K modified to exclude leukopenia, thus mSLEDAI-2K]), and
- No new British Isles Lupus Assessment Group-2004 (BILAG) A organ domain score and not more than one new BILAG B organ domain score compared to baseline, and
- No worsening from baseline in subjects' lupus disease activity, where worsening is defined as an increase ≥ 0.30 points on a 3-point Physician's Global Assessment visual analog scale (PGA VAS), and
- No violation of specified medication rules detailed in the core protocol.
Secondary Outcome Measures :
- Response on BILAG-based Composite Lupus Assessment (BICLA) at Month 12 compared to baseline [ Time Frame: At Month 12 compared to Day 1 (pre-dose baseline) ]
Response on BICLA is defined as:
- Improvement from baseline in disease activity as measured by BILAG. Improvement is defined as a reduction of all baseline BILAG A to B/C/D and baseline BILAG B to C/D and no BILAG worsening in other organ systems, where worsening is defined as ≥ 1 new BILAG A or ≥ 2 new BILAG B, and
- No worsening from baseline in mSLEDAI-2K, where worsening is defined as an increase from baseline of > 0 points in mSLEDAI-2K, and
- No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase of ≥ 0.30 points on a 3-point PGA VAS, and
- No discontinuation of investigational product, and
- No violation of specified medication rules detailed in the core protocol.
- Time to first confirmation of a 4-month sustained modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) response [ Time Frame: Day 1 (pre-dose baseline) to Month 12 ]A response is defined as a reduction of at least 4 points from baseline.
- Time to first confirmation of a 4-month sustained response in mucocutaneous manifestations (i.e., rash, alopecia, mucosal ulcers) [ Time Frame: Day 1 (pre-dose baseline) to Month 12 ]
Response is defined as:
- No increase in the overall mSLEDAI-2K score excluding mucocutaneous manifestations, and
- Remission (score of zero) from baseline in the mSLEDAI-2K score of mucocutaneous manifestations.
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Inclusion criteria at screening:
- Signed Informed Consent Form (ICF) prior to any study-mandated procedure.
- Diagnosis of Systemic Lupus Erythematosus (SLE) made at least 6 months prior to Screening, according to 2019 European League Against Rheumatism / American College of Rheumatology Criteria.
- A modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) score ≥ 6 and clinical mSLEDAI-2K score ≥ 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers). The mSLEDAI-2K score does not include "leukopenia".
- British Isles Lupus Assessment Group-2004 (BILAG) Grade B in ≥ 2 organ systems or a BILAG Grade A in ≥ 1 organ system.
- Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 visual analog scale.
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Currently treated with one or more of the following SLE background medications:
- Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine).
- Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤1.44 g/day).
- Azathioprine (≤ 2 mg/kg/day).
- Methotrexate (≤ 25 mg/week).
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Oral Corticosteroids (OCS):
- if OCS is the only SLE background medication: ≥ 7.5 mg/day and ≤ 30 mg/day prednisone or equivalent.
- if OCS is not the only SLE background medication: ≤ 30 mg/day prednisone or equivalent.
- Belimumab (≤10 mg/kg every 4 weeks intravenously [i.v.], or 200 mg/week subcutaneously [s.c.]).
Treatment with antimalarials, mycophenolate mofetil, mycophenolic acid, azathioprine, methotrexate or belimumab must have been started at least 90 days prior to Screening. Treatment with OCS must have been started at least 30 days prior to Screening.
• For women of childbearing potential (WoCBP):
- Negative serum pregnancy test at Screening.
- Agreement to undertake monthly urine pregnancy tests from Randomization up to 6 months after study treatment discontinuation.
- Agreement to use a highly effective method of contraception from Screening (Visit 1) up to 6 months after study treatment discontinuation.
Inclusion criteria at randomization:
- A clinical mSLEDAI-2K score ≥ 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
- BILAG Grade B in 2 or more organ systems or a BILAG Grade A in 1 or more organ system.
- PGA score ≥ 1.0 on a 0 to 3 visual analog scale.
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Presence of at least one of the following biomarkers of serological evidence of active SLE (in a Screening sample as measured by central laboratory):
- Anti-dsDNA antibodies elevated above normal,
- Antinuclear antibodies with a titer of at least 1:160,
- Anti-Smith antibody elevated above normal.
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Currently treated with one or more of the following SLE background medications that must be stable for at least 30 days prior to Randomization (except OCS, which must be stable for at least 15 days prior to Randomization):
- Antimalarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine);
- Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤ 1.44g/day);
- Azathioprine (≤ 2 mg/kg/day);
- Methotrexate (≤ 25 mg/week);
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OCS:
- if OCS is the only SLE background medication: ≥ 7.5 mg/day and ≤ 30 mg/day prednisone or equivalent.
- if OCS is not the only SLE background medication: ≤ 30 mg/day prednisone or equivalent.
- Belimumab (≤ 10 mg/kg every 4 weeks i.v. or ≤ 200 mg/week s.c.).
- WoCBP must have a negative urine pregnancy test at Randomization.
Main Exclusion Criteria:
- Pregnant, planning to be become pregnant up to Final Study Visit, or lactating women.
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Severe active central nervous system lupus or active severe or unstable neuropsychiatric SLE including but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; or mononeuritis multiplex:
- That would make the subject unable to fully understand the ICF; OR
- Where, in the opinion of the investigator/delegate, protocol-specified standard of care is insufficient and the use of a more aggressive therapeutic approach, such as adding i.v. cyclophosphamide and/or high dose i.v. pulse corticosteroid (CS) therapy or other treatments not permitted in the protocol is indicated.
- A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with psoriasis, rheumatoid arthritis, erosive arthritis, scleroderma, autoimmune hepatitis or uncontrolled autoimmune thyroid disease.
- History or presence of Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, symptomatic bradycardia or syncope associated with cardiac disorders.
- Subjects who experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, vascular thrombosis, decompensated heart failure requiring hospitalization, or heart failure defined by the New York Heart Association Class III/IV within 6 months prior to Screening.
- Resting heart rate < 50 bpm as measured by the 12-lead ECG at Screening or at Randomization.
- An elevated QT interval corrected according to Fridericia's formula (QTcF) interval of > 470 ms (females) / > 450 ms (males) at Screening or at Randomization.
- History or presence of severe respiratory disease or pulmonary fibrosis, based on medical history, lung function, and chest X-ray (or CT scan as per local guidelines), performed at Screening or within 6 months prior to Screening.
- History of clinically relevant bronchial asthma or chronic obstructive pulmonary disease that has required treatment with oral or parenteral CS for more than a total of 2 weeks within the last 6 months prior to Screening.
- History or presence of malignancy (except for surgically excised and non-recurrent cutaneous basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma), lymphoproliferative disease, or history of total lymphoid irradiation within 10 years prior to Screening.
- Presence of macular edema or active uveitis detected by optical coherence tomography (OCT) during screening.
- History of chronic liver or biliary disease (other than Gilbert's Syndrome) or subjects with alanine aminotransferase or aspartate aminotransferase > 3 × Upper Limit of Normal (ULN) or total bilirubin > 1.5 × ULN (unless in the context of known Gilbert's Syndrome).
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Significant hematology abnormality at screening assessment:
- lymphocyte count < 500 /μL (0.5 × 10^9/L);
- hemoglobin < 7 g/dL;
- white blood cell count < 2000/μL (2.0 × 10^9/L); or
- platelets < 25000/μL (25 × 10^9/L).
- Estimated glomerular filtration rate < 15 mL/min/1.73 m^2.
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Treatment with the following medications within 15 days or 5 half-lives of the medication (whichever is longer) prior to Randomization:
- β-blockers, diltiazem, verapamil, digoxin, digitoxin, or any other antiarrhythmic or heart-rate -lowering systemic therapy.
- QT-prolonging drugs with known risk of torsade de pointes irrespective of indication.
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Treatment with the following medications within 30 days or 5 half-lives of the medication (whichever is longer) prior to Randomization:
- Cyclophosphamide, cyclosporine, voclosporin, tacrolimus, sirolimus, etc.
- Pulse methylprednisolone.
- Vaccination with live vaccines (including live vaccines for COVID-19).
- Intra-articular, intramuscular or i.v. CS within 6 weeks prior to Randomization.
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Treatment with the following medications within 90 days or 5 half-lives of the medication (whichever is longer) prior to Randomization:
- Leflunomide.
- i.v. immunoglobulins.
- Treatment with any investigational agent within 90 days or 5 half-lives of the drug (whichever is longer) prior to Randomization.
- Treatment with B cell-depleting biological agents (e.g., rituximab or ocrelizumab) or biological immunosuppressive agents (e.g., anti-tumor necrosis factor [TNF], anti-interleukin [IL]-1, anti-IL6 therapies), within 12 months prior to Randomization.
- Treatment with anifrolumab within 6 months prior to Randomization.
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Treatment with any of the following medications any time prior to Screening:
- Alemtuzumab,
- Sphingosine-1-phosphate receptor modulators (e.g., fingolimod),
- Subjects previously randomized to cenerimod or placebo in any trial involving cenerimod.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05672576
Contacts
| Contact: Idorsia Clinical Trial Information USA | +1 856 661 3721 | idorsiaclinicaltrials@idorsia.com | |
| Contact: Idorsia Clinical Trial Information Europe | + 41 58 844 19 77 | idorsiaclinicaltrials@idorsia.com |
Locations
Show 78 study locations
Sponsors and Collaborators
Idorsia Pharmaceuticals Ltd.
Investigators
| Study Director: | Clinical Trials | Idorsia Pharmaceuticals Ltd. |
| Responsible Party: | Idorsia Pharmaceuticals Ltd. |
| ClinicalTrials.gov Identifier: | NCT05672576 |
| Other Study ID Numbers: |
ID-064A302 2022-002815-47 ( EudraCT Number ) |
| First Posted: | January 5, 2023 Key Record Dates |
| Last Update Posted: | April 24, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Idorsia Pharmaceuticals Ltd.:
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Musculoskeletal and connective tissue disorders Immune System Diseases Autoimmune Diseases |
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |