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A Phase 2 Master Protocol Assessing Inebilizumab and Blinatumomab in Autoimmune Diseases
NCT06570798 · Amgen
In plain English
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Official title
A Phase 2, Open Label, Multicenter, Platform Trial to Assess the Safety, Tolerability, and Efficacy of Inebilizumab and Blinatumomab in Subjects With Autoimmune Diseases
About this study
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
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 design
Enrollment target: 220 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-07-16
Estimated completion: 2029-03-09
Last updated: 2026-02-24
Interventions
Drug: InebilizumabDrug: Blinatumomab
Primary outcomes
- • 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)
Sponsor
Amgen · industry
Contacts & investigators
ContactAmgen Call Center · contact · medinfo@amgen.com · 866-572-6436
InvestigatorMD · study_director, Amgen
All locations (52)
HonorHealth Research and Innovation InstituteRecruiting
Scottsdale, Arizona, United States
University of ColoradoRecruiting
Aurora, Colorado, United States
Vida Research CenterTerminated
Hialeah, Florida, United States
Homestead Associates In Research IncTerminated
Homestead, Florida, United States
Vitaly Clinical ResearchTerminated
Miami, Florida, United States
Bioresearch Partner Coral TerraceRecruiting
South Miami, Florida, United States
University Medical Center New OrleansRecruiting
New Orleans, Louisiana, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Mayo ClinicRecruiting
Rochester, Minnesota, United States
Northwell HealthRecruiting
Great Neck, New York, United States
Westchester Medical CenterRecruiting
Hawthorne, New York, United States
Columbia University Medical CenterRecruiting
New York, New York, United States
University of Rochester Medical CenterRecruiting
Rochester, New York, United States
MetroHealth Medical CenterRecruiting
Cleveland, Ohio, United States
Cleveland Clinic FoundationRecruiting
Cleveland, Ohio, United States
Prolato Clinical Research CenterRecruiting
Houston, Texas, United States
Seattle Rheumatology AssociatesRecruiting
Seattle, Washington, United States
Linear Clinical Research LimitedRecruiting
Perth, Western Australia, Australia
Cliniques Universtaire Saint Luc Universite Catholique de LouvainRecruiting
Brussels, Belgium
Universitair Ziekenhuis GentRecruiting
Ghent, Belgium
Universitair Ziekenhuis Leuven - Campus GasthuisbergRecruiting
Leuven, Belgium
Centre Hospitalier Universitaire de Liege - Sart TilmanRecruiting
Liège, Belgium
Hôpitaux Universitaires Paris Sud - Hôpital BicêtreRecruiting
Le Kremlin-Bicêtre, France
Centre Hospitalier Regional Universitaire de Lille - Hopital Claude HuriezRecruiting
Lille, France
Centre Hospitalier Universitaire de Lyon- Hopital Edouard HerriotRecruiting
Lyon, France
Centre Hospitalier Universitaire de Lyon - Hopital Edouard HerriotRecruiting
Lyon Cédex 3, France
Hopital de la ConceptionRecruiting
Marseille, France
Hopital CochinRecruiting
Paris, France
Hopital Bichat Claude BernardRecruiting
Paris, France
Hopital Europeen Georges PompidouRecruiting
Paris, France
Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital CivilRecruiting
Strasbourg, France
Centre Hospitalier Universitaire de Strasbourg - Hopital de HautepierreRecruiting
Strasbourg, France
Centre Hospitalier Universitaire de Toulouse - Hopital PurpanRecruiting
Toulouse, France
Centre Hospitalier Universitaire de Toulouse - Hopital RangueilRecruiting
Toulouse, France
Krankenhaus Porz am Rhein gGmbHRecruiting
Cologne, Germany
Universitaetsklinikum Duesseldorf AoeRRecruiting
Düsseldorf, Germany
Universitaetsklinikum LeipzigRecruiting
Leipzig, Germany
Klinikum der LMU MuenchenRecruiting
München, Germany
IRCCS Ospedale San RaffaeleRecruiting
Milan, Italy
IRCCS Istituto Clinico HumanitasRecruiting
Rozzano, Italy
Ospedale San Giovanni BoscoRecruiting
Torino, Italy
Unidade Local de Saude de Lisboa Ocidental, EPE - Hospital Santa CruzRecruiting
Carnaxide, Portugal
Unidade Local de Saude de Sao Jose, EPE - Hospital Curry CabralRecruiting
Vila Franca de Xira, Portugal
Unidade Local de Saude de Gaia-Espinho, EPERecruiting
Vila Nova de Gaia, Portugal
Hospital Universitario Marques de ValdecillaRecruiting
Santander, Cantabria, Spain
Hospital Universitari Vall d HebronRecruiting
Barcelona, Catalonia, Spain
Hospital Clinic i Provincial de BarcelonaRecruiting
Barcelona, Catalonia, Spain
Hospital Universitari Vall d HebronRecruiting
Barcelona, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Addenbrookes HospitalRecruiting
Cambridge, United Kingdom
Leicester General HospitalRecruiting
Leicester, United Kingdom
Royal Victoria InfirmaryRecruiting
Newcastle upon Tyne, United Kingdom