A Study of E6742 in Participants With Systemic Lupus Erythematosus

The SRI-4 responder will be defined as a participant meeting all of the following criteria: at least a 4-point reduction from baseline in SLEDAI-2K score; no new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004; no worsening from baseline in participants lupus disease activity defined by an increase >=0.30 points on a 3-point PGA VAS.

Laboratory parameters will include hematology, blood chemistry and urinalysis. Any clinically significant change in laboratory parameters will be determined at the investigator's discretion.

Vital signs will include measurement of body temperature, respiratory rate, sitting blood pressure and pulse rate. Any clinically significant change in vital signs will be determined at the investigator's discretion.

SLEDAI-2K is a scale that stratifies severity of disease activity. It comprises 24 weighted items (16 clinical, 8 laboratory), with individual scores ranging from 1 to 8 and a total score from 0 to 105. Higher scores indicate greater disease activity and more severe organ involvement.

The BILAG-2004 is a validated instrument for assessing systemic lupus erythematosus (SLE) disease activity. It evaluates 97 clinical and laboratory items across one systemic symptom and eight organ systems (mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, hematological). Manifestations in the prior 4 weeks are scored on a 5-point scale (0-4), and each organ/system is categorized into five levels (A-E), ranging from severe activity (A) to never involved (E).

The PGA is a widely used scale in clinical trials to measure overall disease severity as assessed by the physician. It is evaluated on a 10-centimeter (cm) VAS scored from 0 to 3. An increase of >=1 point with a score 2.5 indicates mild to moderate worsening, while a score >2.5 indicates severe worsening. Higher PGA scores reflect greater disease activity.

The CLASI is an assessment scale used to evaluate the disease activity of cutaneous lupus erythematosus (CLE), and it is also commonly used to assess cutaneous manifestation in SLE. It consists of an activity score, an index of the acute phase, and damage score, an index of the chronic phase. The activity score is composed of 4 items: Erythema, scale/hypertrophy, mucous membrane involvement, and alopecia, with a total range of 0-70. The damage score consists of 3 items: Dyspigmentation, scarring/atrophy/panniculitis and scarring of the scalp, with a total range of 0-56. Higher values indicate more severity.

The SLICC/ACR Damage Index is an index to assess organ damage in SLE participants and is composed of 12 evaluation items for organ systems. Irreversible lesions occurring since the onset of SLE and present for at least 6 months are evaluated. The sum of the scores for each dimension represents the degree of impairment for that individual participant. Higher scores indicate more disease severity.

The Lupus-PRO is a validated, SLE specific quality of life instrument consisting of 43 questions. This PRO comprehensively measures a variety of concerns relevant to lupus participants, and the impact of lupus and its treatment on their health-related quality of life (HRQOL), as well as non-health-related quality of life (non-HRQOL).

The FACIT-F is a validated 13-item questionnaire assessing fatigue, with each item rated on a 4-point Likert scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher scores indicating less fatigue and better quality of life

The BICLA is a composite index used to assess disease activity in SLE. A BICLA response is defined as reduction of all baseline BILAG-2004 A to B or C or D; and baseline BILAG-2004 B to C or D; no BILAG-2004 worsening in other organ systems, as defined by >=1 new BILAG-2004 A or >= 2 new BILAG-2004 B; no worsening from baseline in SLEDAI-2K as defined as an increase from baseline of >0 points in SLEDAI-2K; no worsening from baseline in participants lupus disease activity defined by an increase >=0.30 points on a 3-point PGA VAS; and no treatment failure.

The SRI-X responder will be defined as a participant meeting all of the following criteria: at least a X-point reduction from baseline in SLEDAI-2K score; no new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004; no worsening from baseline in participants lupus disease activity defined by an increase >=0.30 points on a 3-point PGA VAS.

LLDAS responder is defined as meeting all of the following criteria: SLEDAI-2K <=4 points, with no activity in major organ systems (renal, central nervous system [CNS], cardiopulmonary, vasculitis, fever); no new lupus disease activity compared with the previous assessment; safety of Estrogen in Systemic Lupus Erythematosus National Assessment (SELENA) - SLEDAI PGA <=1 point; current prednisone (or equivalent) dose <=7.5 mg/day; and standard maintenance doses of immunosuppressive drugs and approved biological agents.

DORIS responder is defined as meeting all of the following criteria: clinical SLEDAI (excluding serology) = 0; PGA VAS score (scale 0-3) less than (<) 0.5; Prednisone (or equivalent) dose less than or equal to (<=) 5 mg/day, and stable antimalarials, immunosuppressives, and biologics.

LLDAS responder is defined as meeting all of the following criteria: SLEDAI-2K <=4 points, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever); no new lupus disease activity compared with the previous assessment; safety of Estrogen in SELENA-SLEDAI PGA <=1 point; current prednisone (or equivalent) dose <=7.5 mg/day; and standard maintenance doses of immunosuppressive drugs and approved biological agents.

DORIS responder is defined as meeting all of the following criteria: clinical SLEDAI (excluding serology) = 0; PGA VAS score (scale 0-3) < 0.5; Prednisone (or equivalent) dose <=5 mg/day, and stable antimalarials, immunosuppressives, and biologics.

The BICLA is a composite index used to assess disease activity in SLE. A BICLA response is defined as reduction of all baseline BILAG-2004 A to B or C or D; and baseline BILAG-2004 B to C or D; no BILAG-2004 worsening in other organ systems, as defined by >=1 new BILAG-2004 A or >= 2 new BILAG-2004 B; no worsening from baseline in SLEDAI-2K as defined as an increase from baseline of >0 points in SLEDAI-2K; no worsening from baseline in participants lupus disease activity defined by an increase >=0.30 points on a 3-point PGA VAS; and no treatment failure.

The SRI-4 responder will be defined as a participant meeting all of the following criteria: at least a 4-point reduction from baseline in SLEDAI-2K score; no new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004; no worsening from baseline in participants lupus disease activity defined by an increase >=0.30 points on a 3-point PGA VAS.

A mild/moderate flare is defined as change in SLEDAI-2K instrument score of 3 points/more (but not to >12); new or worse discoid, photosensitive, profundus, cutaneous vasculitis, bullous lupus; nasopharyngeal ulcers; pleuritis; pericarditis; arthritis; or fever due to SLE; increase in prednisone requirement, but not to >0.5 mg/kg/day; addition of an non-steroidal anti-inflammatory drugs (NSAID) or hydroxychloroquine for SLE activity; >=1.0 increase in PGA score, but not to >2.5. A severe flare is defined as change in SLEDAI-2K instrument score >12 points; new or worse central nervous system SLE; vasculitis; nephritis; myositis; platelets <60,000 /microliter (mcl); or hemolytic anemia with hemoglobin <7.0 gram per deciliter (g/dL) or decrease in hemoglobin >3.0 g/dL; increase in prednisone dose to >0.5 mg/kg/day; new requirement for cyclophosphamide, azathioprine, methotrexate, or mycophenolate for SLE activity; hospitalization for SLE activity; increase in PGA score to >2.5.

A mild flare is defined as appearance of B score due to new or worsening in 1 or more organ system OR appearance of C score due to new or worsening in 3 or more organ systems. A moderate flare is defined as appearance of B score due to new or worsening in 2 or more organ systems. A severe flare is defined as appearance of A score due to new or worsening in any organ system.

CLASI-50 response was defined as a 50% improvement from baseline in CLASI-A score.