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

Официальное название

A Phase 2, Open Label, Multicenter, Platform Trial to Assess the Safety, Tolerability, and Efficacy of Inebilizumab and Blinatumomab in Subjects With Autoimmune Diseases

Обзор

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).

Вмешательства

• Препарат Inebilizumab
  IV Infusion
• Препарат Blinatumomab
  SC Injection

Первичные конечные точки

• Subprotocol A, B Part A, and C Part A: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [Срок оценки: Day 1 to Week 52]
• Subprotocol A, B Part A, and C Part A: Number of Participants Who Experience a Serious TEAE [Срок оценки: Day 1 to Week 52]
• Subprotocol B Part B Subgroup 1: Number of Participants With Complete Renal Response (CRR) [Срок оценки: Week 52]
• Subprotocol B Part B Subgroup 2: Number of Participants With Remission in SLE as Defined by Definition of Remission in SLE (DORIS) [Срок оценки: Week 26]
• Subprotocol C Part B: Percentage of Participants Achieving Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) Remission [Срок оценки: Week 12]

Вторичные конечные точки (12)

• Subprotocol A, B Part A Subgroup 1 and Part B Subgroup 1: Number of Participants With CRR [Срок оценки: 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) [Срок оценки: Week 12, Week 26, Week 38, and Week 52]
• Subprotocol A and B: Number of Participants With Remission in SLE as Defined by DORIS [Срок оценки: 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 and B: Number of Participants With a Lupus Low Disease Activity State (LLDAS) [Срок оценки: Week 12, Week 26, Week 38, and Week 52]
• Subprotocol A and B: Change From Baseline in SLE Activity Index-2000 (SLEDAI-2K) Score [Срок оценки: Week 12, Week 26, Week 38, and Week 52]
• Subprotocol A, B Part A Subgroup 1 and Part B Subgroup 1: Change From Baseline in 24-hour UPCR [Срок оценки: Week 12, Week 26, Week 38, and Week 52]
• Subprotocol A: Maximum Concentration (Cmax) of Inebilizumab [Срок оценки: Day 1 to Week 52]
• Subprotocol A: Time to Cmax (tmax) of Inebilizumab [Срок оценки: Day 1 to Week 52]
• Subprotocol A: Area Under the Concentration-time Curve (AUC) of Inebilizumab [Срок оценки: Day 1 to Week 52]
• Subprotocol B and C: Cmax of Blinatumomab [Срок оценки: up to Week 12]
• Subprotocol B and C: tmax of Blinatumomab [Срок оценки: up to Week 12]
• Subprotocol B and C: AUC of Blinatumomab [Срок оценки: up to Week 12]

Критерии участия

\*Subprotocol A and B are no longer recruiting participants\*

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• HonorHealth Research and Innovation Institute — Scottsdale
• University of Colorado — Aurora
• Vida Research Center — Hialeah
• Homestead Associates In Research Inc — Homestead
• Vitaly Clinical Research — Miami
• Bioresearch Partner Coral Terrace — South Miami
• University Medical Center New Orleans — New Orleans
• Massachusetts General Hospital — Boston
• … и ещё 9 центров

Франция · 12 центров

• Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre — Le Kremlin-Bicêtre
• Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez — Lille
• Centre Hospitalier Universitaire de Lyon- Hopital Edouard Herriot — Lyon
• Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot — Lyon Cédex 3
• Hopital de la Conception — Marseille
• Hopital Cochin — Paris
• Hopital Bichat Claude Bernard — Paris
• Hopital Europeen Georges Pompidou — Paris
• … и ещё 4 центра

Испания · 6 центров

• Hospital Universitario Marques de Valdecilla — Santander
• Hospital Universitari Vall d Hebron — Barcelona
• Hospital Clinic i Provincial de Barcelona — Barcelona
• Hospital Universitari Vall d Hebron — Barcelona
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario 12 de Octubre — Madrid

Бельгия · 4 центра

• Cliniques Universtaire Saint Luc Universite Catholique de Louvain — Brussels
• Universitair Ziekenhuis Gent — Ghent
• Universitair Ziekenhuis Leuven - Campus Gasthuisberg — Leuven
• Centre Hospitalier Universitaire de Liege - Sart Tilman — Liège

Германия · 4 центра

• Krankenhaus Porz am Rhein gGmbH — Cologne
• Universitaetsklinikum Duesseldorf AoeR — Düsseldorf
• Universitaetsklinikum Leipzig — Leipzig
• Klinikum der LMU Muenchen — München

Великобритания · 4 центра

• Addenbrookes Hospital — Cambridge
• Western General hospital — Edinburgh
• Leicester General Hospital — Leicester
• Royal Victoria Infirmary — Newcastle upon Tyne

Италия · 3 центра

• IRCCS Ospedale San Raffaele — Milan
• IRCCS Istituto Clinico Humanitas — Rozzano
• Ospedale San Giovanni Bosco — Turin

Португалия · 3 центра

• Unidade Local de Saude de Lisboa Ocidental, EPE - Hospital Santa Cruz — Carnaxide
• Unidade Local de Saude de Sao Jose, EPE - Hospital Curry Cabral — Vila Franca de Xira
• Unidade Local de Saude de Gaia-Espinho, EPE — Vila Nova de Gaia

ОАЭ · 3 центра

• Sheikh Shakhbout Medical City — Abu Dhabi
• Cleveland Clinic Abu Dhabi — Abu Dhabi
• Al Kuwait Hospital Dubai ehs — Dubai

Австралия · 1 центр

• Linear Clinical Research Limited — Perth

Публикации

• Karam S, Boudhabhay I, Jhaveri KD. Bispecific Antibodies for Glomerular Diseases: Are We Ready for Prime Time? J Am Soc Nephrol. 2026 Apr 14. doi: 10.1681/ASN.0000001120. Online ahead of print. No abstract available. PMID 41979896

Идентификаторы

NCT: NCT06570798 · 20240033 · 2024-514382-19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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