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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus; Active Refractory Rheumatoid Arthritis
• Intervention / Treatment: Drug: Blinatumomab; Drug: Inebilizumab

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research Limited
• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universtaire Saint Luc Universite Catholique de Louvain
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Liège, Belgium, 4000
    • Recruiting
    • Centre Hospitalier Universitaire de Liege - Sart Tilman
• France
  • Le Kremlin-Bicêtre, France, 94270
    • Recruiting
    • Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre
  • Lille, France, 59037
    • Recruiting
    • Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
  • Lyon, France, 69437
    • Recruiting
    • Centre Hospitalier Universitaire de Lyon- Hopital Edouard Herriot
  • Lyon Cédex 3, France, 69437
    • Recruiting
    • Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot
  • Marseille, France, 13005
    • Recruiting
    • Hôpital de La Conception
  • Paris, France, 75014
    • Recruiting
    • Hôpital Cochin
  • Paris, France, 75908
    • Recruiting
    • Hôpital Europeen Georges Pompidou
  • Paris, France, 75018
    • Recruiting
    • Hopital Bichat Claude Bernard
  • Strasbourg, France, 67091
    • Recruiting
    • Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital Civil
  • Strasbourg, France, 67098
    • Recruiting
    • Centre Hospitalier Universitaire de Strasbourg - Hopital de Hautepierre
  • Toulouse, France, 31059
    • Recruiting
    • Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
  • Toulouse, France, 31059
    • Recruiting
    • Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil
• Germany
  • Cologne, Germany, 51149
    • Recruiting
    • Krankenhaus Porz am Rhein gGmbH
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitaetsklinikum Duesseldorf AoeR
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitaetsklinikum Leipzig
  • München, Germany, 80336
    • Recruiting
    • Klinikum der LMU Muenchen
• Italy
  • Milan, Italy, 20132
    • Recruiting
    • IRCCS Ospedale San Raffaele
  • Rozzano, Italy, 20089
    • Recruiting
    • IRCCS Istituto Clinico Humanitas
  • Turin, Italy, 10154
    • Recruiting
    • Ospedale San Giovanni Bosco
• Portugal
  • Carnaxide, Portugal, 2790-134
    • Recruiting
    • Unidade Local de Saude de Lisboa Ocidental, EPE - Hospital Santa Cruz
  • Vila Franca de Xira, Portugal, 2600-076
    • Recruiting
    • Unidade Local de Saude de Sao Jose, EPE - Hospital Curry Cabral
  • Vila Nova de Gaia, Portugal, 4430-502
    • Recruiting
    • Unidade Local de Saude de Gaia-Espinho, EPE
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Hospital Universitario Marqués de Valdecilla
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
    • Barcelona, Catalonia, Spain, 08036
      • Recruiting
      • Hospital Clínic I Provincial de Barcelona
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates, 11001
    • Recruiting
    • Sheikh Shakhbout Medical City
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Addenbrookes Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • Western General Hospital
  • Leicester, United Kingdom, LE5 4PW
    • Recruiting
    • Leicester General Hospital
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Royal Victoria Infirmary
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • HonorHealth Research and Innovation Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
  • Florida
    • Hialeah, Florida, United States, 33010
      • Terminated
      • Vida Research Center
    • Homestead, Florida, United States, 33033
      • Terminated
      • Homestead Associates in Research Inc
    • Miami, Florida, United States, 33125
      • Terminated
      • Vitaly Clinical Research
    • South Miami, Florida, United States, 33143
      • Recruiting
      • Bioresearch Partner Coral Terrace
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • University Medical Center New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • New York
    • Great Neck, New York, United States, 11021
      • Recruiting
      • Northwell Health
    • Hawthorne, New York, United States, 10532
      • Recruiting
      • Westchester Medical Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44109
      • Recruiting
      • MetroHealth Medical Center
  • Texas
    • Houston, Texas, United States, 77054
      • Recruiting
      • Prolato Clinical Research Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Seattle Rheumatology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

*Subprotocol B is 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subprotocol A: Inebilizumab 3 Doses; Participants will receive 3 doses of inebilizumab administered via an intravenous (IV) infusion.	Drug: Inebilizumab; IV Infusion; Other Names: Uplizna®
Experimental: Subprotocol A: Inebilizumab 4 Doses; Participants will receive 4 doses of inebilizumab administered via an IV infusion.	Drug: Inebilizumab; IV Infusion; Other Names: Uplizna®
Experimental: Subprotocol B Part A: Blinatumomab Low-dose; Participants will receive blinatumomab low-dose administered via SC injection.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol B Part A: Blinatumomab Medium-dose; Participants will receive blinatumomab medium-dose administered via SC injection.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol B Part A: Blinatumomab High-dose; Participants will receive blinatumomab high-dose administered via SC injection.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol B Part B: Dose Expansion; Participants will receive blinatumomab at a dose which will be determined during Subprotocol B Part A.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol C Part A: Blinatumomab Low-dose; Participants will receive blinatumomab low-dose administered via SC injection during Subprotocol C Part A.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol C Part A: Blinatumomab Medium-dose; Participants will receive blinatumomab medium-dose administered via SC injection during Subprotocol C Part A.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol C Part A: Blinatumomab High-dose; Participants will receive blinatumomab high-dose administered via SC injection during Subprotocol C Part A.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®
Experimental: Subprotocol C Part B: Dose Expansion; Participants will receive blinatumomab at a dose which will be determined during Subprotocol C Part A.	Drug: Blinatumomab; SC Injection; Other Names: Blincyto®

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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 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 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, 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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2025
• Primary Completion (Estimated): July 21, 2028
• Study Completion (Estimated): July 21, 2028

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; Systemic lupus erythematosus; Blinatumomab; Inebilizumab; Active refractory rheumatoid arthritis
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Antineoplastic Agents; blinatumomab; inebilizumab
• Other Study ID Numbers: 20240033; 2024-514382-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this trial will be considered beginning 18 months after the trial has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this trial.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen trial/trials in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No