\*Subprotocol A and B are no longer recruiting participants\*
Inclusion Criteria:
- Subprotocol A and B: Diagnosis of SLE according to 2019 European League Against Rheumatism and the American College of Rheumatology (ACR) classification criteria.
- Subprotocol A and B: Participant must be positive for at least one of the following autoantibodies at screening (performed by central laboratory) or through documented history:
1. Antinuclear antibodies (ANA) ≥ 1:80
2. Anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies elevated to above normal range (ie, positive results)
3. AntiSmith antibodies elevated to above normal (ie, positive results).
- Subprotocol A and B (Subgroup 1): Active, biopsy-proven, proliferative LN demonstrating class III or class IV with or without co-existing features of Class V LN (or pure Class V LN for Subprotocol B only) according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria. The local biopsy report will be used.
- Subprotocol A and B: SLE Disease Activity Index 2K ≥ 6.
- Subprotocol A and B (Subgroup 1): Inadequate response, loss of response or intolerance to at least 1 therapy (Subprotocol A) or 2 immunosuppressive therapies (Subprotocol B Subgroup 1) at the maximally tolerated doses as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (KDIGO, 2024). Inadequate response is defined as: UPCR ≥ 1.0 mg/mg.
- Subprotocol B (Subgroup 2): Refractory SLE participants with inadequate response to multiple therapies (excluding hydroxychloroquine or corticosteroids) and have failed either a biologic agent or cyclophosphamide.
- Subprotocol B (Part B Subgroup 2): British Isles Lupus Assessment Group (BILAG)-2004 level A disease in 1 organ system or BILAG-2004 level B disease in ≥ 2 organ systems
- Subprotocol B (Part B Subgroup 2): Physician Global Assessment (PGA) ≥ 1
- Subprotocol A and B: If receiving any of the following medications, participants must be on these doses prior to Day 1:
1. Prednisone dose ≤ 20 mg/day (or its equivalent in other corticosteroid forms) and at a stable dose for 5 days
2. Hydroxychloroquine dose ≤ 400 mg/day and at a stable dose for 4 weeks. Other equivalent antimalarials (chloroquine, quinacrine) are also accepted at a stable dose for 4 weeks.
3. MMF dose ≤ 3 g/day or MPA dose ≤ 2160 mg/day and at a stable dose for 2 weeks.
4. AZA dose ≤ 2 mg/kg/day and at a stable dose for 2 weeks.
5. Methotrexate > 25 mg/week and at a stable dose for 2 weeks
6. Leflunomide > 20 mg/day and at a stable dose for 2 weeks
7. Dapsone > 300 mg/day and at a stable dose for 2 weeks.
- Subprotocol C (Part A and Part B): Diagnosis of RA according to the 2010 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria.
- Subprotocol C (Part A and Part B): Moderate to severe disease activity as defined by DAS28-CRP > 3.2 with ≥ 3 swollen joints and ≥ 3 tender joints (based on 28 joint counts) at screening.
- Subprotocol C (Part A and Part B): Refractory disease defined as:
- Active disease despite having received treatment with:
1. at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD), AND
2. at least 2 biologic disease-modifying antirheumatic drugs (bDMARDs) of different mechanisms of action OR 1 bDMARD and at least 1 targeted synthetic disease-modifying antirheumatic drugs (tsDMARD).
- Inadequate response or intolerance to csDMARDs, bDMARDs, and tsDMARDs should be defined as:
1. Participant having active disease despite a minimum of 12 weeks of treatment with a csDMARD, bDMARD, or tsDMARD.
2. Intolerance to treatment as defined by participant having experienced an adverse effect from treatment with a csDMARD, bDMARD, or tsDMARD.
- Subprotocol C (Part B): High sensitivity C-Reactive Protein (hsCRP) level ≥ upper limit of normal per the central laboratory at screening.
Exclusion Criteria:
- Subprotocol A, B and C: Receipt of a live and/or live attenuated vaccine within 4 weeks prior to first dose of trial drug, during the treatment period, or until B-cell repletion after the end of the treatment period. Administration of inactivated (killed) vaccines is acceptable.
- Subprotocol A and B: Estimated glomerular filtration rate (eGFR) of < 30 mL per minute per 1.73 m\^2 of body surface area (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula, with screening laboratory results for serum creatinine value).
- Subprotocol A and B: Significant likely irreversible organ damage related to SLE (eg, end-stage renal disease \[ESRD\]).
- Subprotocol A and B: Any acute, severe lupus related flare during screening that needs immediate treatment.
- Subprotocol A and B: A previous kidney transplant or planned transplant within trial treatment period.
- Subprotocol A and B: History of or current renal diseases (Parts A and B, Subgroup 1) that in the opinion of the investigator could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy).
- Subprotocol A: Renal biopsy showing pure class V.
- Subprotocol B: Active CNS Lupus within one year prior to screening.
- Subprotocol B and C: History or presence of clinically relevant central nervous system (CNS) pathology or event such as seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or organic brain syndrome.
- Subprotocol C: Prior history of current inflammatory joint disease other than RA including but not limited to SLE, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (eg, vasculitis, pulmonary fibrosis, or Felty's syndrome).
- Subprotocol C: Functional Class IV as defined by the ACR classification of functional status in RA.
- Subprotocol A, B and C: Receipt of the following medications or treatments at any time prior to Day 1:
1. B-cell directed CAR T-cell and T-cell engager therapies
2. Total lymphoid irradiation
3. Bone marrow transplant
4. T-cell vaccination therapy
5. Natalizumab