Systemic Lupus Erythematosus
Conditions
Interventions
E6742 (Dose A/ Dose B/ Dose C) or Placebo will be orally administered.
Sponsors
Tago Fumitoshi
Japan Agency for Medical Research and Development (AMED)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female adult, age >=18 years and =1 organ system or BILAG-2004 category B in >=2 organ systems at Screening 4. Systemic Lupus Erythematosus Disease Activity Index 2000 (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): a. Oral Corticosteroid (<=30 mg/day, prednisone or equivalent): The dosing regimen should be stable for at least 4 weeks before the first dose of study drug. b. 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. c. 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
Exclusion criteria: 1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [beta-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: a. 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 b. Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation. c. 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 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. 4. Drug-induced lupus erythematosus 5. Active or unstable neuropsychiatric lupus (including but not limited to any condition defined by BILAG category A in neuropsychiatric organ system) 6. 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 - Sjogren's syndrome secondary to SLE - Antiphospholipid antibody syndrome (APS) secondary to SLE - Mixed Connective Tissue Disease (MCTD) not meeting diagnostic criteria for PM and SSc 7. 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. 8. Laboratory test results meeting any of the following criteria at Screening: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) - Absolute neutrophil count (ANC) 2.0 g/gCr - Estimated glomerular filtration rate (eGFR) (Modification of Diet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants who Achieve a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response with Low Dose of Oral Corticosteroid (OCS) (Prednisone or Equivalent) at Week 24 | — |
Secondary
| Measure | 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 - Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent SAEs - Each value and change from baseline of laboratory parameters and vital signs - Frequency and percentage of abnormal findings of 12-lead ECG parameters, ophthalmic examination, and chest X-rays - Percentage of Participants with Low Dose of OCS (Prednisone or Equivalent) at Week 24 - Change From Baseline in SLEDAI-2K - Change From Baseline in BILAG-2004 - Change From Baseline in Physician Global Assessment (PGA) - Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) - Change From Baseline in Joint Count Change From Baseline in Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) Damage Index - Change From Baseline in Autoantibody - Change From Baseline in Complements (C3 and C4) - Change From Baseline in Lupus-Patient-Reported Outcomes (Lupus-PRO) - Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) - Percentage of Participants who Achieve a BICLA Response - Percentage of Participants who Achieve a SLE Responder Index- X (SRI-X) Response - Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) - Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) Remission - Duration in a LLDAS - Duration in a DORIS Remission - Time to First Response of BICLA - Time to First Response of SRI-4 - Percentage of Participants with mild/Moderate, or Severe Flares Assessed by Hybrid Safety of Estrogen in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index - Percentage of Participants with Mild, Moderate, or Severe Flares Assessed by BILAG- 2004 Flare - Percentage of Participants who Achieve a CLASI-50 Response - Plasma concentrations of E6742 | — |
Contacts
Public ContactInquiry service
Eisai Co., Ltd.
Outcome results
None listed