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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| E6742 Dose A | Experimental |
| |
| E6742 Dose B | Experimental |
| |
| E6742 Dose C | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E6742 | Drug | E6742 oral tablets. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants who Achieve a BICLA Response with Low Dose of OCS (Prednisone or Equivalent) 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. | At Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants who Achieve an SLE Responder Index- 4 (SRI-4) Response with Low Dose of OCS (Prednisone or Equivalent) 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. |
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Inclusion Criteria:
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
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
At least BILAG-2004 category A in >=1 organ system or BILAG-2004 category B in >=2 organ systems at screening
SLEDAI-2K score >=6 points at Screening AND Clinical SLEDAI-2K score >=4 points at Baseline
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):
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.
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.
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
Willing and able to provide written informed consent and comply with all aspects of the protocol
Exclusion Criteria
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.
Females of childbearing potential who:
Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation.
Participants on an oral contraceptive must use an additional barrier method throughout the study and for 28 days after study drug discontinuation.
Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (ie, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation). No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation.
Drug-induced lupus erythematosus
Active or unstable neuropsychiatric lupus (including but not limited to any condition defined by BILAG category A in neuropsychiatric organ system)
Systemic autoimmune diseases other than SLE (eg, rheumatoid arthritis, Crohn's disease, systemic sclerosis [SSc], multiple sclerosis, polymyositis/ dermatomyositis [PM/DM]) that may affect the assessment of SLE pathology at Screening. The participants with the following diseases may be included in the study
Any clinically significant symptom or organ impairment found by chest X-ray, ophthalmic examination, vital signs, or ECG finding at Screening or Baseline, laboratory test at Screening that in the opinion of the investigator could affect the participants safety or interfere with the study assessments.
Laboratory test results meeting any of the following criteria at Screening:
Renal impairment falling under any of the following criteria at Screening:
Received vaccination within 2 weeks before the first dose of study drug (4 weeks before in case of live/ live attenuated vaccines)
Currently or previously receiving gene therapy for SLE (eg, CAR-T cell therapy)
Currently enrolled in another clinical study or used any investigational drug or device (including E6742) within 28 days (or 5× the half-life, whichever is longer) before obtaining informed consent
Any history of the following clinically significant infections:
Any findings indicating a history of tuberculosis on chest X-ray at Screening
Positive or repeated hold (indeterminate or intermediate) in tuberculosis test (Interferon-γ release assays) at Screening
A prolonged QTc interval calculated using Fridericia's formula (QTcF) greater than 450 millisecond (ms) according to central reading at Screening. If the QTcF machine read is greater than 440 ms on the first single 12-lead ECG, 2 additional 12-lead ECGs will be performed 1 minute apart and the mean of the 3 QTcF values will be used for evaluation.
A prolonged QTcF interval (mean QTcF >450 ms) as demonstrated by triplicated ECGs at Baseline. Has any risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QTcF interval (excluding hydroxychloroquine).
Hypersensitivity to the study drug, drug product chemical derivate or any of the excipients at Screening
Any history of or concomitant medical condition that in the opinion of the investigators would compromise the participants ability to safely complete the study
Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery which requires only local anesthesia and that can be undertaken as a day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the investigator this operation does not interfere with study procedures and participant safety
Positive on test at Screening for human immunodeficiency virus (HIV)
Positive on test at Screening for hepatitis B virus (HBV) with a detectable (eg, hepatitis B virus surface [HBs] antigen reactive, HBs antibody, hepatitis B virus core [HBc] antibody, HBV deoxyribose nucleic acid (DNA)) or hepatitis C virus (HCV) with a detectable (eg, HCV ribonucleic acid (RNA) [qualitative], HCV antibody) viral load
Psychotic disorders or unstable recurrent affective disorders evident by use of antipsychotics within 2 years before Screening
History of drug or alcohol dependency or abuse within 2 years before Screening
History or concurrent of malignancy, lymphoma, leukemia, or lymphoproliferative disease (except for basal cell skin cancer, squamous cell skin cancer, and cervical cancer that have been cured by surgical operation)
Assessed to be inappropriate for clinical study by investigators
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Contact | +1-888-274-2378 | esi_medinfo@eisai.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Bengbu Medical University | Not yet recruiting | Bengbu | Anhui | China | ||
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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| Placebo |
| Other |
Placebo oral tablets. |
|
| At Week 24 |
| 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 | Laboratory parameters will include hematology, blood chemistry and urinalysis. Any clinically significant change in laboratory parameters will be determined at the investigator's discretion. | From baseline up to 52 weeks |
| Number of Participants With Clinically Significant Changes in Vital Signs | 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. | From baseline up to 52 weeks |
| 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 | 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. | Baseline, at Week 24 |
| Change From Baseline in BILAG-2004 | 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). | Baseline, at Week 24 |
| Change From Baseline in PGA | 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. | Baseline, at Week 24 |
| Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) | 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. | Baseline, at Week 24 |
| 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) | 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. | Baseline, at Week 24 |
| 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) | 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). | Baseline, at Week 24 |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) | 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 | Baseline, at Week 24 |
| Percentage of Participants who Achieve a BICLA Response | 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. | At Week 24 |
| Percentage of Participants who Achieve a SLE Responder Index- X (SRI-X) Response | 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. | At Week 24 |
| Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) | 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. | At Week 24 |
| Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) Remission | 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. | At Week 24 |
| Duration in a LLDAS | 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. | Week 24 |
| Duration in a DORIS Remission | 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. | Week 24 |
| Time to First Response of BICLA | 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. | Week 24 |
| Time to First Response of SRI-4 | 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. | Week 24 |
| Percentage of Participants with mild/Moderate, or Severe Flares Assessed by Hybrid SELENA-SLEDAI Flare Index | 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. | At Week 24 |
| Percentage of Participants with Mild, Moderate, or Severe Flares Assessed by BILAG- 2004 Flare | 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. | At Week 24 |
| Percentage of Participants who Achieve a CLASI-50 Response | CLASI-50 response was defined as a 50% improvement from baseline in CLASI-A score. | At Week 24 |
| Plasma concentrations of E6742 | Up to 24 weeks |
| Peking Union Medical College Hospital - East Campus |
| Recruiting |
| Beijing |
| Beijing Municipality |
| China |
| Nanfang Hospital Southern Medical University - PPDS | Recruiting | Guangzhou | Guangdong | China |
| The Third Affiliated Hospital, Sun Yat-Sen University | Not yet recruiting | Guangzhou | Guangdong | China |
| The First Affiliated Hospital of Shantou University Medical College | Recruiting | Shantou | Guangdong | China |
| The First Affiliated Hospital of Guangxi Medical University | Recruiting | Nanning | Guangxi | China |
| The Affiliated Hospital of Guizhou Medical University | Recruiting | Guiyang | Guizhou | China |
| Yichang Central People's Hospital - Xiling Campus | Not yet recruiting | Yichang | Hubei | China |
| The Second Xiangya Hospital of Central South University | Not yet recruiting | Changsha | Hunan | China |
| Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School-Main | Not yet recruiting | Nanjing | Jiangsu | China |
| The First Affiliated Hospital of Soochow University - Pinghailu Campus | Not yet recruiting | Suzhou | Jiangsu | China |
| The Second Affiliated Hospital of Soochow University | Recruiting | Suzhou | Jiangsu | China |
| Jiujiang No.1 People's Hospital | Not yet recruiting | Jiujiang | Jiangxi | China |
| The First Affiliated Hospital of Nanchang University - Donghu Campus | Recruiting | Nanchang | Jiangxi | China |
| Pingxiang People's Hospital | Recruiting | Pingxiang | Jiangxi | China |
| Jilin Province People's Hospital | Not yet recruiting | Changchun | Jilin | China |
| First Hospital of Shanxi Medical University | Not yet recruiting | Taiyuan | Shanxi | China |
| Shanxi Bethune Hospital | Not yet recruiting | Taiyuan | Shanxi | China |
| The Second Affiliated Hospital, Zhejiang University School of Medicine - Jiefanglu Campus | Recruiting | Hangzhou | Zhejiang | China |
| Daido Clinic | Recruiting | Nagoya | Aichi-ken | Japan |
| Japan Community Health Care Organization (JCHO) Chukyo Hospital | Recruiting | Nagoya | Aichi-ken | Japan |
| Fujita Health University Hospital | Recruiting | Toyoake | Aichi-ken | Japan |
| University of Occupational and Environmental Health University Hospital | Recruiting | Kitakyushu | Fukuoka | Japan |
| Hokkaido University Hospital | Recruiting | Sapporo | Hokkaidô | Japan |
| Kobe University Hospital | Recruiting | Kobe | Hyôgo | Japan |
| Hyogo Medical University Hospital | Recruiting | Nishinomiya | Hyōgo | Japan |
| Tohoku Medical and Pharmaceutical University Hospital | Recruiting | Sendai | Miyagi | Japan |
| Shinkenko Clinic | Recruiting | Naha | Okinawa | Japan |
| Dokkyo Medical University Hospital | Not yet recruiting | Mibu-Machi, Shimotsugagun | Tochigi | Japan |
| Juntendo University Hospital | Recruiting | Bunkyo | Tokyo | Japan |
| Tokyo Metropolitan Tama Medical Center | Recruiting | Fuchū | Tokyo | Japan |
| Toho University Omori Medical Center | Recruiting | Ōta-ku | Tokyo | Japan |
| Japan Institute for Health Security National Center for Global Health and Medicine | Recruiting | Shinjuku | Tokyo | Japan |
| National Hospital Organization Kyushu Medical Center | Recruiting | Fukuoka | Japan |
| Hiroshima Prefectural Hospital | Recruiting | Hiroshima | Japan |
| Kumamoto Shinto General Hospital | Recruiting | Kumamoto | Japan |
| Niigata University Medical and Dental Hospital | Recruiting | Niigata | Japan |
| Chonnam National University Hospital | Not yet recruiting | Gwangju | South Korea |
| Kaohsiung Veterans General Hospital | Recruiting | Kaohsiung City | Taiwan |
| Taipei Veterans General Hospital | Not yet recruiting | Taipei | Taiwan |
| Chang Gung Memorial Hospital, Linkou | Not yet recruiting | Taoyuan | Taiwan |
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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