The primary purpose of the study is to evaluate the safety and tolerability of multiple oral doses of E6742 in participants with systemic lupus erythematosus (SLE).

Inclusion Criteria:

1. Male or Female, age greater than or equal to (>=) 18 years and less than or equal to (<=) 75 years at the time of written informed consent

2. Body mass index (BMI) >=15 kilogram per square meter (kg/m^2) and less than (<) 30 kg/m^2 at screening

3. Diagnosed with SLE according to 2019 The European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria, Systemic Lupus International Collaborating Clinics Disease Index (SLICC) classification criteria (2012 version), or 1997 revised ACR classification criteria at least 6 months before the informed consent

4. Meets at least one of the following criteria at screening:

   • Antinuclear antibody positive (>=1:80)
   • Anti-double stranded deoxyribonucleic acid (DNA) antibody positive
   • Anti-smith antibody positive

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:

   • 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 or intrauterine hormone-releasing system (IUS)
   • a contraceptive implant
   • an oral contraceptive (Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 28 days after study drug discontinuation)
   • have a vasectomized partner with confirmed azoospermia
   • Do not agree to use a highly effective method of contraception (as described above) 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 NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Approved or certificated for drugs or medical devices in Japan

3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, 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. Any history of surgery that may affect pharmacokinetic (PK) profiles of E6742 (example, hepatectomy, nephrectomy, digestive organ resection) at screening

5. Scheduled for surgery during the study

6. A prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) (Fridericia method) interval (QTcF greater than [>] 450 millisecond [ms]) as demonstrated by a repeated ECG at screening or baseline. A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QTcF interval except for hydroxychloroquine

7. Psychotic disorders or unstable recurrent affective disorders evident by use of antipsychotics within 2 years before screening

8. History of drug or alcohol dependency or abuse within 2 years before screening

9. History of drug allergy or allergy to any investigational product excipients at screening

10. Known to be human immunodeficiency virus (HIV) positive at screening

11. Positive on test at screening for hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis B virus core antibody (HBc antibody), hepatitis B virus DNA (HBV DNA), hepatitis C virus antibody (HCV antibody), human T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis

12. History of clinically significant infections such as latent infectious viruses

13. History of infections requiring hospitalization or intravenous antibiotics, or administration of antiviral drugs, within 4 weeks before the first dose of study drug

14. History of active tuberculosis

15. Any findings indicating a history of tuberculosis on chest X-ray at screening

16. Currently enrolled in another clinical study or used any investigational drug or device within 16 weeks (or 5 half-lives, whichever is longer) before informed consent

17. Received vaccination within 4 weeks before the study treatment (8 weeks before in case of live vaccine)

18. Any history of or concomitant medical condition that in the opinion of the investigators would compromise the participant's ability to safely complete the study

19. Any clinically significant symptom or organ impairment

20. Drug induced lupus erythematosus

21. Active or unstable neuropsychiatric lupus

22. Renal impairment at Screening

23. Systemic autoimmune diseases other than SLE (example, rheumatoid arthritis, Crohn's disease, scleroderma, multiple sclerosis.) that may affect the assessment of SLE pathology

24. History of or complications from 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)

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.