NCT06570798招募中2 期
A Phase 2, Open Label, Multicenter, Platform Trial to Assess the Safety, Tolerability, and Efficacy of Inebilizumab and Blinatumomab in Subjects With Autoimmune Diseases
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 220
- 试验地点
- 104
- 主要终点
- Subprotocol A, B Part A, and C Part A: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
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 Part A) and in adult participants with active refractory rheumatoid arthritis (RA) (Subprotocol C Part A). The trial will also assess the efficacy of SC blinatumomab in adult participants with active and refractory SLE with and without nephritis (Subprotocol B Part B and Subprotocol C Part B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •*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:
- •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 ≥
- •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.
排除标准
- •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:
- •B-cell directed CAR T-cell and T-cell engager therapies
- •Total lymphoid irradiation
- •Bone marrow transplant
- •T-cell vaccination therapy
- •Natalizumab
研究组 & 干预措施
Subprotocol C Part A: Blinatumomab Medium-dose
Experimental
Participants will receive blinatumomab medium-dose administered via SC injection during Subprotocol C Part A.
干预措施: Blinatumomab (Drug)
Subprotocol B Part B: Dose Expansion
Experimental
Participants will receive blinatumomab at a dose which will be determined during Subprotocol B Part A.
干预措施: Blinatumomab (Drug)
Subprotocol A: Inebilizumab 4 Doses
Experimental
Participants will receive 4 doses of inebilizumab administered via an IV infusion.
干预措施: Inebilizumab (Drug)
Subprotocol A: Inebilizumab 3 Doses
Experimental
Participants will receive 3 doses of inebilizumab administered via an intravenous (IV) infusion.
干预措施: Inebilizumab (Drug)
Subprotocol C Part A: Blinatumomab High-dose
Experimental
Participants will receive blinatumomab high-dose administered via SC injection during Subprotocol C Part A.
干预措施: Blinatumomab (Drug)
Subprotocol B Part A: Blinatumomab Medium-dose
Experimental
Participants will receive blinatumomab medium-dose administered via SC injection.
干预措施: Blinatumomab (Drug)
Subprotocol B Part A: Blinatumomab Low-dose
Experimental
Participants will receive blinatumomab low-dose administered via SC injection.
干预措施: Blinatumomab (Drug)
Subprotocol C Part B: Dose Expansion
Experimental
Participants will receive blinatumomab at a dose which will be determined during Subprotocol C Part A.
干预措施: Blinatumomab (Drug)
Subprotocol B Part A: Blinatumomab High-dose
Experimental
Participants will receive blinatumomab high-dose administered via SC injection.
干预措施: Blinatumomab (Drug)
Subprotocol C Part A: Blinatumomab Low-dose
Experimental
Participants will receive blinatumomab low-dose administered via SC injection during Subprotocol C Part A.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Subprotocol A, B Part A, and C Part A: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
时间窗: Day 1 to Week 52
Subprotocol A, B Part A, and C Part A: Number of Participants Who Experience a Serious TEAE
时间窗: Day 1 to Week 52
Subprotocol B Part B Subgroup 1: Number of Participants With Complete Renal Response (CRR)
时间窗: Week 52
Subprotocol B Part B Subgroup 2: Number of Participants With Remission in SLE as Defined by Definition of Remission in SLE (DORIS)
时间窗: Week 26
Subprotocol C Part B: Percentage of Participants Achieving Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) Remission
时间窗: Week 12
次要结局
- 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)
- 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: Number of Participants With Anti-inebilizumab Antibody Formation(Day 1 to 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: 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: Number of Participants With Anti-blinatumomab Antibody Formation(Day 1 to Week 52)
- Subprotocol B and C: Cmax of Blinatumomab(up to Week 12)
- Subprotocol B and C: tmax of Blinatumomab(up to Week 12)
- Subprotocol B and C: AUC of Blinatumomab(up to Week 12)
- Subprotocol A, B Part A Subgroup 1 and Part B Subgroup 1: Number of Participants With CRR(Subprotocol A and B Part A: Week 12, Week 26, Week 38, and Week 52; Subprotocol B Part B: Week 12, Week 26, and Week 38)
- Subprotocol A, B Part A Subgroup 1 and Part B Subgroup 1: 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 DORIS(Subprotocol A, B Part A, and B Part B Subgroup 1: Week 12, Week 26, Week 38, and Week 52; Subprotocol B Part B Subgroup 2: Week 12, Week 38, and Week 52)
- Subprotocol A, B Part A Subgroup 1 and Part B Subgroup 1: Change From Baseline in 24-hour UPCR(Week 12, Week 26, Week 38, and Week 52)
- Subprotocol B and C: Cmax of Blinatumomab(Day 1 up to Week 52)
- Subprotocol B and C: tmax of Blinatumomab(Day 1 up to Week 52)
- Subprotocol B and C: AUC of Blinatumomab(Day 1 up to Week 52)
- Subprotocol C Part A: Percentage of Participants Achieving DAS28-CRP < 2.6(Week 12 and Week 26)
- Subprotocol C Part A: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) ≤ 2.8(Week 12 and Week 26)
- Subprotocol C Part A: 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)
- Subprotocol B Part B and C Part B: Number of Participants Who Experience a TEAE(Day 1 to Week 52)
- Subprotocol B Part B and C Part B: Number of Participants Who Experience a Serious TEAE(Day 1 to Week 52)
- Subprotocol B Part A Subgroup 1 and Part B Subgroup 1: Number of Participants With Primary Efficacy Renal Response (PERR)(Week 12, Week 26, Week 38, and Week 52)
- Subprotocol B Part B Subgroup 2: Number of Participants Who are Responders as Defined by SLE Responder Index 4 (SRI-4)(Week 12, Week 26, Week 38, and Week 52)
- Subprotocol B Part B Subgroup 2: Number of Participants Who are Responders as Defined by SRI-6(Week 12, Week 26, Week 38, and Week 52)
- Subprotocol B Part B Subgroup 2: Number of Participants Who are Responders as Defined by SRI-8(Week 12, Week 26, Week 38, and Week 52)
- Subprotocol B Part B Subgroup 2: Number of Participants Who are Responders as Defined by BILAG-based Combined Lupus Assessment (BICLA)(Week 12, Week 26, Week 38, and Week 52)
- Subprotocol C Part B: Percentage of Participants Achieving DAS28-CRP Remission at Week 26(Week 26)
- Subprotocol C Part B: Percentage of Participants Achieving CDAI Remission at Weeks 12 and 26(Week 12 and Week 26)
- Subprotocol C Part B: Percentage of Participants Achieving SDAI Remission at Weeks 12 and 26(Week 12 and Week 26)
- Subprotocol C Part B: Percentage of Participants Who Achieve DAS28-CRP Remission at Week 12 and Sustain Remission at Weeks 26, 38, and 52(Week 12, Week 26, Week 38, and Week 52)
研究者
研究点 (104)
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