A Phase 2/3, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Emapalumab in Adult Patients With Hemophagocytic Lymphohistiocytosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Overall Response
研究概览
简要总结
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with secondary HLH.
详细描述
Study NI-0501-10 is an open-label, single arm, multicenter, Phase 2/3 interventional study.
The study enrolls adult patients with hemophagocytic lymphohistiocytosis (HLH), specifically newly diagnosed patients with malignancy-associated HLH (M-HLH), and newly diagnosed or previously treated patients with non-malignancy-associated HLH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients of age 18 and older at the time of HLH diagnosis
- •Fulfilment of 5 of the 8 HLH-2004 clinical criteria
- •Patients diagnosed with malignancy-associated HLH must be treatment naïve; patients diagnosed with HLH driven by any other etiology or idiopathic can be either treatment naïve or treatment experienced
- •Patients with non-malignancy-associated or idiopathic HLH who have already received conventional therapy for HLH must have failed prior treatment as per the treating physician's judgement
- •Informed consent signed by the patient or by the patient's legally authorized representative(s) (as required by local law)
- •Willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug, if female and of childbearing potential.
排除标准
- •Primary HLH
- •Current or scheduled administration of therapies known to trigger the cytokine release syndrome (e.g. chimeric antigen receptor (CAR)-modified T cells, bispecific T cell-engaging antibodies)
- •Current or scheduled administration of PD-1/PD-L1/CTLA-4 inhibitors
- •Life-expectancy associated with the underlying disease (triggering HLH) < 3 months
- •Ongoing participation in an investigational trial, or administration of any investigational treatment within 30 days
- •History of hypersensitivity or allergy to any components of emapalumab
- •Active mycobacteria, Histoplasma capsulatum, or Leishmania infections
- •Evidence of latent tuberculosis
- •Receipt of a bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening
- •Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to Screening
研究组 & 干预措施
Emapalumab
Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.
干预措施: Emapalumab-Lzsg (Drug)
结局指标
主要结局
Overall Response
时间窗: Week 4
Achievement of either a Complete or Partial Response Complete Response is adjudicated if the following are observed: * No fever = body temperature \<37.5°C * Normal spleen size * No cytopenia = Absolute Neutrophil Counts \>=1.0x10\^9/L and platelet count \>=100x10\^9/L \[absence of G-CSF and transfusion support must be documented for at least 4 days to report no cytopenia\] * No hyperferritinemia = serum level is \<2000 µg/L * No evidence of coagulopathy, i.e., normal D-Dimer and/or normal (\>150 mg/dL) fibrinogen levels * No neurological and CSF abnormalities attributed to HLH * No sustained worsening of sCD25 (as indicated by at least two consecutive measurements that are \>2-fold higher than baseline) Partial Response is adjudicated if there is an improvement (\>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities).
次要结局
- Duration of Response(Up to 1 year after last emapalumab administration)
- Best Response on Treatment(Week 4; End of Treatment Visit (on average of 12 weeks))
- Overall Response(End of Treatment Visit (on average of 12 weeks))
- Hemophagocytic Lymphohistiocytosis Relapse(Up to 1 year after last emapalumab administration)
- Serum Concentrations of Emapalumab(Up to 1 year after last emapalumab administration)
- Serum Biomarker Levels(Up to 1 year after last emapalumab administration)
- Overall Survival(End of Treatment Visit (on average of 12 weeks))
- Time to Complete Response or Partial Response(Week 4; End of Treatment visit (on average of 12 weeks))
- Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events(Up to 1 year after last emapalumab administration)
- Incidence of Anti-Drug Antibodies Against Emapalumab(Up to 1 year after last emapalumab administration)