Systemic Lupus Erythematosus
Conditions
Sponsors
Seabrook Tim
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Inclusion Criteria: Screening criteria: - Signed and dated ICF prior to any study-mandated procedure. - Male and female subjects aged from 18 (or higher if the local age of consent is greater) to 75 years old (inclusive) at the time of signing the ICF. - Diagnosis of SLE made at least 6 months prior to Screening, according to 2019 European League Against Rheumatism / American College of Rheumatology Criteria. - An 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"". - BILAG Grade B in >= 2 organ systems or a BILAG Grade A in >= 1 organ system. - PGA score >= 1.0 on a 0 to 3 VAS. - Currently treated with one or more of the following SLE background medications: - Antimalarials: (= 7.5 mg/day and = 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers). - BILAG Grade B in >= 2 organ systems or a BILAG Grade A in >= 1 organ system. - PGA score >= 1.0 on a 0 to 3 VAS. - 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 (ANA) with a titer of at least 1:160. - Anti-Smith (anti-Sm) antibody elevated above normal. - 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 (= 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 pregnan
Exclusion criteria
Exclusion criteria: Main Exclusion Criteria: - Pregnant, planning to be become pregnant up to FSV, or lactating women. - 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 (AV) 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 HR 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 (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN (unless in the context of known Gilbert's Syndrome). - Significant hematology abnormality at screening assessment: - Lymphocyte count < 500 /uL (0.5 x 109/L); - Hemoglobin < 7 g/dL; - White blood cell count < 2000/uL (2.0 x 109/L) or - Platelets < 25,000/uL (25 x 109/L). - Estimated glomerular filtration rate < 15 mL/min/1.73 m2. - Treatment with the following medications within 15 days or 5 half-lives of the medication (whichever is longer) prior to Randomization: - beta-blockers, diltiazem, verapamil, digoxin, digitoxin*, or any other anti-a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response on Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 12 compared to baseline, defined as meeting all of the following criteria: - Reduction from baseline of at least 4 points in the modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K; i.e., based on the SLEDAI-2K, modified to exclude leukopenia). 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 (PGA) visual analog scale (VAS). and - No violation of specified medication rules detailed in the core protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Response on British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Month 12 compared to baseline, defined as follows: - Improvement from baseline in disease activity as measured by BILAG Improvement is defined as a reduction of all baseline BILAGA 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 patients' lupus disease activity, where worsening is defined as an increase >= 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 mSLEDAI-2K response, 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), 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. | — |
Countries
Argentina, Brazil, Bulgaria, Colombia, France, Greece, India, Japan, Mexico, Philippines, Poland, Romania, South Korea, Taiwan, Thailand, Ukraine, United States
Contacts
Public Contactfor OPUS Japan Contact Point
Linical Co., Ltd.
Outcome results
None listed