A Phase 2 Master Protocol Assessing Inebilizumab and Blinatumomab in Autoimmune Diseases

Inclusion Criteria29

• 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:
• Antinuclear antibodies (ANA) ≥ 1:80
• Anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies elevated to above normal range (ie, positive results)
• 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:
• Prednisone dose ≤ 20 mg/day (or its equivalent in other corticosteroid forms) and at a stable dose for 5 days
• 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.
• MMF dose ≤ 3 g/day or MPA dose ≤ 2160 mg/day and at a stable dose for 2 weeks.
• AZA dose ≤ 2 mg/kg/day and at a stable dose for 2 weeks.
• Methotrexate \> 25 mg/week and at a stable dose for 2 weeks
• Leflunomide \> 20 mg/day and at a stable dose for 2 weeks
• 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:
• at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD), AND
• 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:
• Participant having active disease despite a minimum of 12 weeks of treatment with a csDMARD, bDMARD, or tsDMARD.
• 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.