A Phase 2a Master Protocol Assessing Inebilizumab and Blinatumomab in Autoimmune Diseases
- Conditions
- Systemic Lupus ErythematosusActive Refractory Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT06570798
- Lead Sponsor
- Amgen
- Brief Summary
The main objective is to assess the safety and tolerability of inebilizumab in adult participants with active and refractory systemic lupus erythematosus (SLE) with nephritis (Subprotocol A) and to assess the safety and tolerability of subcutaneous (SC) blinatumomab in adult participants with active and refractory SLE with and without nephritis (Subprotocol B) and in adult participants with active refractory rheumatoid arthritis (RA) (Subprotocol C).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 98
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Subprotocol A and B: Diagnosis of SLE according to 2019 European League Against Rheumatism and the American College of Rheumatology (ACR) classification criteria.
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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)
- Anti-Smith antibodies elevated to above normal (ie, positive results).
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Subprotocol A and B (with LN): 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.
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Subprotocol A and B (with LN): Inadequate response, loss of response or intolerance to at least 1 therapy (Subprotocol A) or 2 immunosuppressive therapies (Subprotocol B with LN) 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.
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Subprotocol B (SLE without nephritis): Systemic Lupus Erythematosus Disease Activity Index 2K ≥ 6.
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Subprotocol B (SLE without nephritis): Refractory SLE participants with inadequate response to multiple therapies (excluding hydroxychloroquine or corticosteroids) and have failed either a biologic agent or cyclophosphamide.
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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.
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Subprotocol C: Diagnosis of RA according to the 2010 ACR/ European Alliance of Associations for Rheumatology (EULAR) classification criteria.
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Subprotocol C: Active disease defined as DAS28-CRP > 3.2 with at least 1 swollen joint at screening.
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Subprotocol C: Refractory disease defined as:
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Moderate to severe 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).
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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 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 study treatment period.
- Subprotocol A and B: History of or current renal diseases (other than LN) 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 C: Prior history of current inflammatory joint disease other than RA including but not limited to systemic lupus erythematosus, 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Subprotocol A: Inebilizumab 3 Doses Inebilizumab Participants will receive 3 doses of inebilizumab administered via an intravenous (IV) infusion. Subprotocol A: Inebilizumab 4 Doses Inebilizumab Participants will receive 4 doses of inebilizumab administered via an IV infusion. Subprotocol B: Blinatumomab Low-dose Blinatumomab Participants will receive blinatumomab low-dose administered via SC injection. Subprotocol B: Blinatumomab Medium-dose Blinatumomab Participants will receive blinatumomab medium-dose administered via SC injection. Subprotocol B: Blinatumomab High-dose Blinatumomab Participants will receive blinatumomab high-dose administered via SC injection. Subprotocol C: Blinatumomab Low-dose Blinatumomab Participants will receive blinatumomab low-dose administered via SC injection. Subprotocol C: Blinatumomab Medium-dose Blinatumomab Participants will receive blinatumomab medium-dose administered via SC injection. Subprotocol C: Blinatumomab High-dose Blinatumomab Participants will receive blinatumomab high-dose administered via SC injection.
- Primary Outcome Measures
Name Time Method Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) Day 1 to Week 52 Number of Participants Who Experience a Serious TEAE Day 1 to Week 52
- Secondary Outcome Measures
Name Time Method Subprotocol A and B: Number of Participants With Complete Renal Response (CRR) Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Number of Participants With Partial Renal Response (PRR) Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Number of Participants With Remission in SLE as Defined by Definition of Remission in SLE (DORIS) Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Number of Participants With a Lupus Low Disease Activity State (LLDAS) Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Change From Baseline in SLE Activity Index-2000 (SLEDAI-2K) Score Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Percent Change From Baseline in SLEDAI-2K Score Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Change From Baseline in 24-hour UPCR Week 12, Week 26, Week 38, and Week 52 Subprotocol A and B: Percent Change From Baseline in 24-hour UPCR Week 12, Week 26, Week 38, and Week 52 Subprotocol A: Maximum Concentration (Cmax) of Inebilizumab Day 1 to Week 52 Subprotocol A: Time to Cmax (tmax) of Inebilizumab Day 1 to Week 52 Subprotocol A: Area Under the Concentration-time Curve (AUC) of Inebilizumab Day 1 to Week 52 Subprotocol B and C: Cmax of Blinatumomab Day 1 to Week 12 Subprotocol B and C: tmax of Blinatumomab Day 1 to Week 12 Subprotocol B and C: AUC of Blinatumomab Day 1 to Week 12 Subprotocol A: Number of Participants With Anti-inebilizumab Antibody Formation Day 1 to Week 52 Subprotocol B and C: Number of Participants With Anti-blinatumomab Antibody Formation Day 1 to Week 52 Subprotocol C: Percentage of participants achieving Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) < 2.6 Week 12 and Week 26 Subprotocol C: Percentage of participants achieving Clinical Disease Activity Index (CDAI) ≤ 2.8 Week 12 and Week 26 Subprotocol C: Percentage of participants achieving Simplified Disease Activity Index (SDAI) ≤ 3.3 Week 12 and Week 26 Subprotocol C: Percentage of participants achieving American College of Rheumatology (ACR)20 response Week 12 and Week 26 Subprotocol C: Percentage of participants achieving ACR50 response Week 12 and Week 26 Subprotocol C: Percentage of participants achieving ACR70 response Week 12 and Week 26
Trial Locations
- Locations (40)
Linear Clinical Research Limited
🇦🇺Perth, Western Australia, Australia
Krankenhaus Porz am Rhein gGmbH
🇩🇪Cologne, Germany
HonorHealth Research and Innovation Institute
🇺🇸Scottsdale, Arizona, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Vida Research Center
🇺🇸Hialeah, Florida, United States
Homestead Associates In Research Inc
🇺🇸Homestead, Florida, United States
Vitaly Clinical Research
🇺🇸Miami, Florida, United States
Northwell Health
🇺🇸Great Neck, New York, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Prolato Clinical Research Center
🇺🇸Houston, Texas, United States
Scroll for more (30 remaining)Linear Clinical Research Limited🇦🇺Perth, Western Australia, Australia