Open-label, 4-Part Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Alnuctamab (BMS-986349/CC-93269) in Participants With Moderate to Severe Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Number of treatment emergent AEs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Participants with Lupus
This study drug will be done by sentinel dosing (study drug given to a small number of participants to watch closely) before all the participants receive the study drug.
干预措施: Alnuctamab (Drug)
结局指标
主要结局
Number of treatment emergent AEs
时间窗: 9 days
Type, frequency, and severity of treatment emergent AEs, SAEs, DLTs, and AEs of special interest (e.g., CRS, ICANS)
次要结局
- Maximum concentration of Alnuctamab(0-29 days)
- Change in SLE Responder Index (SRI) rate(Baseline, Week 24 and Week 52)
研究者
Chrisanna Dobrowolski
Senior Assistant Professor
Icahn School of Medicine at Mount Sinai