Systemic Lupus Erythematosus
Conditions
Brief summary
The main purpose of the study is to demonstrate the efficacy based on dose response of E6742 compared with placebo as defined by the proportion of participants achieving a response using the British Isles Lupus Assessment Group (BILAG) based Composite Lupus Assessment (BICLA) with a low dose of oral corticosteroids (OCS) (prednisone or equivalent) at Week 24 in participants with systemic lupus erythematosus (SLE).
Interventions
DRUGE6742
E6742 oral tablets.
OTHERPlacebo
Placebo oral tablets.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female adult, age \>=18 years (the minimum age may be different from 18 years in certain countries based on regional requirements) and \<=75 years at the time of informed consent 2. Diagnosed with SLE at least 6 months before the informed consent AND fulfill the 2019 EULAR/ACR classification criteria at Screening based on medical history 3. At least BILAG-2004 category A in \>=1 organ system or BILAG-2004 category B in \>=2 organ systems at screening 4. SLEDAI-2K score \>=6 points at Screening AND Clinical SLEDAI-2K score \>=4 points at Baseline 5. Receiving at least one of the following treatments for SLE (if more than 1 treatment is used, all medications must be within the dosage defined in the protocol): 1. OCS (\<=30 mg/day, prednisone or equivalent): The dosing regimen should be stable for at least 4 weeks before the first dose of study drug. 2. Oral hydroxychloroquine (\<=400 mg/day), quinacrine (\<=200 mg/day): These medications should have been initiated or discontinued at least 12 weeks before the first dose of study drug, and the dosing regimen should remain stable for at least 8 weeks before the first dose. 3. Immunosuppressants: The following medications should have been initiated or discontinued at least 12 weeks before the first dose of study drug, and the dosing regimen should remain stable for at least 8 weeks before the first dose * Mycophenolate mofetil (\<=3 g/day) * Mycophenolate sodium (\<=2160 mg/day) * Azathioprine (\<=200 mg/day) * 6-mercaptopurine (\<=100 mg/day) * Methotrexate (oral/subcutaneous/intramuscular) (\<=25 mg/week) 6. Willing and able to provide written informed consent and comply with all aspects of the protocol
Exclusion criteria
1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[ß-hCG\] or human chorionic gonadotropin \[hCG\] test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 2. Females of childbearing potential who: 1. Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: * Total abstinence (if it is their preferred and usual lifestyle) * An intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) * A contraceptive implant * Combined estrogen and progestogen-containing hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation, such as desogestrel (oral, injectable). Participants using hormonal contraceptives must be on a stable dose of the same contraceptive product for at least 28 days before dosing, throughout the study, and for at least 28 days following study drug discontinuation. * Have a vasectomized partner with confirmed azoospermia 2. Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation. 3. Participants on an oral contraceptive must use an additional barrier method throughout the study and for 28 days after study drug discontinuation. 3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve a BICLA Response with Low Dose of OCS (Prednisone or Equivalent) at Week 24 | At Week 24 | 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 greater than or equal to (\>=1) new BILAG-2004 A or \>= 2 new BILAG-2004 B; no worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) as defined as an increase from baseline of greater than (\>) 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 Physician Global Assessment Visual Analogue Scale (PGA VAS); and no treatment failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve an SLE Responder Index- 4 (SRI-4) Response with Low Dose of OCS (Prednisone or Equivalent) at Week 24 | At Week 24 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent SAEs | From baseline up to 52 weeks | — |
| Number of Participants With Clinically Significant Changes in Laboratory Parameters | From baseline up to 52 weeks | Laboratory parameters will include hematology, blood chemistry and urinalysis. Any clinically significant change in laboratory parameters will be determined at the investigator's discretion. |
| Number of Participants With Clinically Significant Changes in Vital Signs | From baseline up to 52 weeks | 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. |
| Frequency and Percentage of Abnormal Findings in 12-lead Electrocardiogram (ECG) Parameters | From baseline up to 52 weeks | — |
| Frequency and Percentage of Abnormal Findings in Ophthalmic Examination | From baseline up to Week 48 | — |
| Frequency and Percentage of Abnormal Findings in Chest X-rays | From baseline up to Week 48 | — |
| Percentage of Participants with Low Dose of OCS (Prednisone or Equivalent) at Week 24 | At Week 24 | — |
| Change From Baseline in SLEDAI-2K | Baseline, at Week 24 | 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. |
| Change From Baseline in BILAG-2004 | Baseline, at Week 24 | 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). |
| Change From Baseline in PGA | Baseline, at Week 24 | 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. |
| Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) | Baseline, at Week 24 | 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. |
| Change From Baseline in Joint Count | Baseline, at Week 24 | — |
| Change From Baseline in Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) Damage Index) | Baseline, at Week 24 | 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. |
| Change From Baseline in Autoantibody | Baseline, at Week 24 | — |
| Change From Baseline in Complements (C3 and C4) | Baseline, at Week 24 | — |
| Change From Baseline in Lupus-Patient-Reported Outcomes (Lupus-PRO) | Baseline, at Week 24 | 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). |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) | Baseline, at Week 24 | 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 |
| Percentage of Participants who Achieve a BICLA Response | At Week 24 | 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. |
| Percentage of Participants who Achieve a SLE Responder Index- X (SRI-X) Response | At Week 24 | 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. |
| Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) | At Week 24 | 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. |
| Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) Remission | At Week 24 | 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. |
| Duration in a LLDAS | Week 24 | 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. |
| Duration in a DORIS Remission | Week 24 | 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. |
| Time to First Response of BICLA | Week 24 | 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. |
| Time to First Response of SRI-4 | Week 24 | 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. |
| Percentage of Participants with mild/Moderate, or Severe Flares Assessed by Hybrid SELENA-SLEDAI Flare Index | At Week 24 | 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. |
| Percentage of Participants with Mild, Moderate, or Severe Flares Assessed by BILAG- 2004 Flare | At Week 24 | 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. |
| Percentage of Participants who Achieve a CLASI-50 Response | At Week 24 | CLASI-50 response was defined as a 50% improvement from baseline in CLASI-A score. |
| Plasma concentrations of E6742 | Up to 24 weeks | — |
Countries
China, Japan, South Korea, Taiwan
Contacts
CONTACTEisai Medical Information
Outcome results
None listed