Systemic Lupus Erythematosus
Conditions
Keywords
Refractory, Systemic Lupus Erythematosus (SLE), Severe Refractory Systemic Lupus Erythematosus
Brief summary
This study will assess the safety and preliminary efficacy of the bi-specific TCE, alnuctamab (known as BMS-986349, CC-93269, EM901), targeting BCMA in patients with moderate to severe SLE, refractory to standard-of-care treatments.
Detailed description
The purpose of this research study is for researchers to learn if the investigational therapy called alnuctamab (known as BMS-986349, CC-93269, EM901) is safe and effective to treat refractory Systemic Lupus Erythematosus (SLE). CC-93269 is investigational, which means its safety and effectiveness have not been established and it is not approved by the U.S. Food and Drug Administration (FDA) for SLE. This will be the first study testing CC-93269 in SLE. Alnuctumab is a type of treatment known as a T cell engager. It is a special protein engineered in the laboratory, which is able to attach to T cells, a type of white blood cell that can kill other cells in the body. T cells normally protect the body from infections, for example by destroying the cells where the virus hides. In this case, alnuctumab will redirect T cells to a new target, called the plasma B cell. This is a type of white blood cell that plays an important role in activating the autoimmune response in patients with lupus. By linking T cells to the autoimmune plasma B cells, alnuctumab will allow the removal of these pathogenic cells. The goal is to evaluate whether this will be sufficient and safe to treat lupus.
Interventions
DRUGAlnuctamab
The study drug will be given as an injection under the skin. For the first 9 days after the CC-93269 injection, subjects will be staying in the hospital. The goal of this study is to determine the optimal dose of CC-93269 to be safely administered to participants.
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age 18-60 years. * Documented diagnosis of SLE fulfilling 2019 ACR/EULAR criteria. * Historical documentation of ANA (1:80 or greater) autoantibody on immunofluorescence as well as presence of at least 1 additional autoantibody of the type: anti-dsDNA, anti-histone, anti-chromatin, anti-Smith, anti-RNP, anti-Ro/SSA, anti-La/SSB, anti-cardiolipin (IgG), or anti-beta2-glycoprotein1 (IgG). * History of SLE that is refractory to corticosteroids and at least 2 immunosuppressive therapies with different mechanisms of action (methotrexate, thiopurines, mycophenolate mofetil, calcineurin inhibitors, biologic agents, cyclophosphamide), including at least one biologic therapy (e.g. anti-CD20 therapy, anifrolumab, belimumab) or cyclophosphamide. Of note, hydroxychloroquine is not considered an immunosuppressive therapy, and methotrexate/azathioprine counts as a single drug class). * Total SLEDAI-2K \>6 with clinical SLEDAI-2K \>4, or \>1 BILAG A organ domain score, or \>2 BILAG B, but without active central nervous system (CNS) disease within the past year; a maximum of two participants with only arthritis and/or rash can be included if truly disabling Key
Exclusion criteria
* Autoimmune disease other than SLE, except associated Sjogren's Disease if not primary contributor to symptoms; coexistent fibromyalgia will be allowed if not primary contributor to symptoms. * TTP-like SLE; catastrophic APS; LN WHO class V as primary qualifying criterion (unless overlap with Class III or IV), rapidly progressive LN, or eGFR \<40 mL/min; active CNS pathology attributable to neuropsychiatric SLE. * Active or suspected infection, including HIV. * O2 sat \<92% on room air; ANC \<1500u/L, Hgb \<8g/dL, Plt \<75,000/uL; ALT or AST \> 2X ULN (unless attributed to active myositis), Total Bilirubin \>1.5 X ULN (unless Gilbert's Disease), total B cell count \<12/microliter, hypogammaglobinemia \<500mg/dL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment emergent AEs | 9 days | Type, frequency, and severity of treatment emergent AEs, SAEs, DLTs, and AEs of special interest (e.g., CRS, ICANS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration of Alnuctamab | 0-29 days | The maximum concentration of Alnuctamab (Cmax) following multiple subcutaneous (SC) administrations in participants with moderate to severe SLE refractory to standard therapy |
| Change in SLE Responder Index (SRI) rate | Baseline, Week 24 and Week 52 | SLE Responder Index (SRI) rate at Week 24, Week 52 compared to baseline SRI is defined as the proportion of participants achieving ≥4 point reduction in SLEDAI-2K \[Systemic Lupus Erythematosus Disease Activity Index\], with no new A organ domain score, ≤ 1 new BILAG \[British Isles Lupus Assessment Group\] B score, and no worsening of the Physician Global Assessment (PGA) score SLEDAI-2K: Total score ranges from 0-105 with higher score indicating greater disease activity BILAG: B Score implies need for a modest dose of steroids. PGA: Score range from -3 (poorer health outcome) to 3 (better health outcome) |
Countries
United States
Contacts
CONTACTChrisanna Dobrowolski, MD
PRINCIPAL_INVESTIGATORChrisanna Dobrowolski, MD
Icahn School of Medicine at Mount Sinai School
Outcome results
None listed