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NCT06570798PHASE2Recruiting

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

Amgen

Start Date

7/16/2025

Completion Date

8/6/2028

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 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).

Eligibility Criteria

Age Range: 18 years to 75 years

\*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: 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

Interventions

DRUG

Inebilizumab

DRUG

Blinatumomab

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Conditions

Systemic Lupus ErythematosusActive Refractory Rheumatoid Arthritis

Locations

HonorHealth Research and Innovation Institute

Scottsdale, Arizona 85258

United States

University of Colorado

Aurora, Colorado 80045

United States

Vida Research Center

Hialeah, Florida 33010

United States

Homestead Associates In Research Inc

Homestead, Florida 33033

United States

Vitaly Clinical Research

Miami, Florida 33125

United States

Bioresearch Partner Coral Terrace

South Miami, Florida 33143

United States

University Medical Center New Orleans

New Orleans, Louisiana 70112

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Northwell Health

Great Neck, New York 11021

United States

Westchester Medical Center

Hawthorne, New York 10532

United States

Columbia University Medical Center

New York, New York 10032

United States

University of Rochester Medical Center

Rochester, New York 14642

United States

MetroHealth Medical Center

Cleveland, Ohio 44109

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

Prolato Clinical Research Center

Houston, Texas 77054

United States

Seattle Rheumatology Associates

Seattle, Washington 98104

United States

Linear Clinical Research Limited

Perth, Western Australia 6009

Australia

Cliniques Universtaire Saint Luc Universite Catholique de Louvain

Brussels, 1200

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000

Belgium

Centre Hospitalier Universitaire de Liege - Sart Tilman

Liège, 4000

Belgium

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre

Le Kremlin-Bicêtre, 94270

France

Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez

Lille, 59037

France

Centre Hospitalier Universitaire de Lyon- Hopital Edouard Herriot

Lyon, 69437

France

Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot

Lyon Cédex 3, 69437

France

Hopital de la Conception

Marseille, 13005

France

Hopital Cochin

Paris, 75014

France

Hopital Bichat Claude Bernard

Paris, 75018

France

Hopital Europeen Georges Pompidou

Paris, 75908

France

Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital Civil

Strasbourg, 67091

France

Centre Hospitalier Universitaire de Strasbourg - Hopital de Hautepierre

Strasbourg, 67098

France

Centre Hospitalier Universitaire de Toulouse - Hopital Purpan

Toulouse, 31059

France

Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil

Toulouse, 31059

France

Krankenhaus Porz am Rhein gGmbH

Cologne, 51149

Germany

Universitaetsklinikum Duesseldorf AoeR

Düsseldorf, 40225

Germany

Universitaetsklinikum Leipzig

Leipzig, 04103

Germany

Klinikum der LMU Muenchen

München, 80336

Germany

IRCCS Ospedale San Raffaele

Milan, 20132

Italy

IRCCS Istituto Clinico Humanitas

Rozzano, 20089

Italy

Ospedale San Giovanni Bosco

Turin, 10154

Italy

Unidade Local de Saude de Lisboa Ocidental, EPE - Hospital Santa Cruz

Carnaxide, 2790-134

Portugal

Unidade Local de Saude de Sao Jose, EPE - Hospital Curry Cabral

Vila Franca de Xira, 2600-076

Portugal

Unidade Local de Saude de Gaia-Espinho, EPE

Vila Nova de Gaia, 4430-502

Portugal

Hospital Universitario Marques de Valdecilla

Santander, Cantabria 39008

Spain

Hospital Universitari Vall d Hebron

Barcelona, Catalonia 08035

Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia 08036

Spain

Hospital Universitari Vall d Hebron

Barcelona, 08035

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Sheikh Shakhbout Medical City

Abu Dhabi, 11001

United Arab Emirates

Cleveland Clinic Abu Dhabi

Abu Dhabi,

United Arab Emirates

Al Kuwait Hospital Dubai ehs

Dubai, 22241

United Arab Emirates

Addenbrookes Hospital

Cambridge, CB2 0QQ

United Kingdom

Western General hospital

Edinburgh, EH4 2XU

United Kingdom

Leicester General Hospital

Leicester, LE5 4PW

United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, NE7 7DN

United Kingdom