Lupus Erythematosus, Systemic
Conditions
Sponsors
Yokoyama Yoshinari
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main 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 Analogue Scale (VAS). $ Currently treated with one or more of the following SLE background medications: - Anti-malarials (=> if OCS is the only SLE background medication: >= 7.5 mg/day and => if OCS is not the only SLE background medication: == 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers). $ British Isles Lupus Assessment Group-2004 (BILAG) Grade B in 2 or more organ systems or a BILAG Grade A in 1 or more organ system. $ Physician's Global Assessment (PGA) score >= 1.0 on a 0 to 3 visual analog scale. $ Presence of at least one of the following items of serological evidence of active SLE or biological variables predictive of Type 1 Interferon (IFN-1) high signature (in a Screening sample as measured by central laboratory): - Anti-dsDNA antibodies elevated to above normal, - Complement C3 12.5 mg/mmol (110.5 mg/g). $ Currently treated with one or more of the following SLE background m
Exclusion criteria
Exclusion criteria: Main Exclusion Criteria: $ Pregnant, planning to be become pregnant up to Final Study Visit or lactating women. $ Severe central nervous system lupus or active severe or unstable neuropsychiatric SLE characterized by: 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 Principal Investigator, 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 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 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 basal or squamous cell skin or mucosal lesions, including dysplasia and carcinoma in situ), lymphoproliferative disease, or history of total lymphoid irradiation. $ 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). $ Significant hematology abnormality at screening assessment: - lymphocyte count < 500 /micro L (0.5 * 10^9/L); - hemoglobin < 7 g/dL; - white blood cell count < 2000/micro L (2.0 * 10^9/L); or - platelets < 25000/micro L (25 * 10^9/L) at screening assessment. $ 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 antiarrhythmic or heart-rate -lowering systemic therapy. - QT-prolonging drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline to Month 12 in the modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) score [ Time Frame: Day 1 (pre-dose baseline) to Month 12 ] This endpoint is based on the SLEDAI-2K index, modified to exclude leukopenia. All values of mSLEDAI-2K from baseline through Month 12 visits will be accounted for in the assessment of this endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| $ Response on Systemic Lupus Erythematosus Responder Index (SRI) at Month 12 [ Time Frame: Day 1 (pre-dose baseline) to Month 12 ] Response on SRI-4 is defined as: - Reduction from baseline of at least 4 points in the 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, and - No violation of protocol-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. 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. Response is defined as: - No increase in the overall mSLEDAI-2K score, and - Remission (score of zero) from baseline in the mSLEDAI-2K score of mucocutaneous manifestations. | — |
Countries
Africa region, Asia-Pacific region, European region, Japan, North Central South America, United States
Contacts
Public ContactYoshinari Yokoyama
Idorsia Pharmaceuticals Japan Ltd.
Outcome results
None listed