Inclusion Criteria:

• 1. Participants must have a diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus for at least 6 months.
• 2. Participants must have elevated anti- double stranded deoxyribonucleic acid (anti-dsDNA) and/or elevated anti-Smith antibody test at Screening (a single retest of previously positive participants who were negative at screening will be allowed).
• 3. Participants with diabetes or hypothyroidism should have well-controlled disease, with stable medications for at least 4 weeks prior to screening.
• 4. Participants who despite at least 2 lines of prior standard immunosuppressive therapies for ≥12 weeks have:
• 1. A Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥8 (including at least 4 points from non-laboratory assessments; excluding alopecia, mucosal ulcers, and fever) and at least 2 British Isles Lupus Assessment Group B (BILAG B) organ system scores and/or
• 2. At least one British Isles Lupus Assessment Group A (BILAG A) organ system score, including cardiac (peri- or myocarditis), respiratory (pleuritis or lung involvement), vascular and renal

Exclusion Criteria:

• 1. Unable to washout prohibited or maintain stable allowed SLE therapy for 4 weeks prior to LDC therapy.
• 2. Participants on hemodialysis.
• 3. Participants with active lupus nephritis (prior history of biopsy-documented International Society of Nephrology/Renal Pathology Society Class VI Lupus Nephritis).
• 4. Recent or clinically significant central nervous system (CNS) disease, including but not limited to cerebrovascular accident, epilepsy, severe brain injury, dementia, Parkinson's disease, cerebellar disease, seizures, organic brain syndrome, lupus headache, or psychosis at any time prior to study.
• 5. Participants with BILAG A for neuropsychiatric SLE.
• 6. Thromboembolic events within last 12 months.
• 7. Participants with severe hepatic dysfunction, defined as grade C-Child-Pugh.
• 8. Diagnosis of drug-induced SLE rather than idiopathic SLE.
• 9. Participants with either proteinuria \>3 grams per day (g/day), or a urinary protein creatinine ratio (UPCR) of \>3 grams per gram (g/g). At least 2 measurements of proteinuria or UPCR over the past 6 months is required to confirm control of renal disease.
• 10. Study participant with chronic kidney failure stage 4, manifested by estimated glomerular filtration rate \<45 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) (measured by Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation), or serum creatinine \>2.5 milligrams per deciliter (mg/dL).