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 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
* Sjögren'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) \>3× upper limit of normal (ULN)
* Absolute neutrophil count (ANC) \<1,000 /mcL
* Platelet count \<50,000 /mcL
* Hemoglobin \<8.0 g/dL
9. Renal impairment falling under any of the following criteria at Screening:
* Urine protein/creatinine ratio \>2.0 g/gCr
* Estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease \[MDRD\]) \<40 mL/min/1.73 m\^2
10. Received vaccination within 2 weeks before the first dose of study drug (4 weeks before in case of live/ live attenuated vaccines)
11. Currently or previously receiving gene therapy for SLE (eg, CAR-T cell therapy)
12. 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
13. Any history of the following clinically significant infections:
* Infections requiring hospitalization or intravenous antibiotics, or administration of antiviral drugs, within 4 weeks before the first dose of study drug
* Active tuberculosis
14. Any findings indicating a history of tuberculosis on chest X-ray at Screening
15. Positive or repeated hold (indeterminate or intermediate) in tuberculosis test (Interferon-γ release assays) at Screening
16. 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.
17. 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).
18. Hypersensitivity to the study drug, drug product chemical derivate or any of the excipients at Screening
19. Any history of or concomitant medical condition that in the opinion of the investigators would compromise the participants ability to safely complete the study
20. 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
21. Positive on test at Screening for human immunodeficiency virus (HIV)
22. 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
23. Psychotic disorders or unstable recurrent affective disorders evident by use of antipsychotics within 2 years before Screening
24. History of drug or alcohol dependency or abuse within 2 years before Screening
25. 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)
26. Assessed to be inappropriate for clinical study by investigators
