A Phase 2/3 Open-label Single Arm Multicentre Study to Assess Safety Tolerability Pharmacokinetics and Efficacy of i.v. Administrations of NI-0501 an Anti-IFNγ mAb in Paediatric Patients With Primary Haemophagocytic Lymphohistiocytosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 40
- 主要终点
- Overall Response Rate (ORR) Second Line
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.
详细描述
The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.
All participants in the NI-0501-04 study (NCT01818492) were invited to participate in the long-term follow-up study NI-0501-05 (NCT02069899). For the primary completion date, mentioned here, we refer to the NI-0501-04 study, even though in accordance with the NI-0501-04 study objectives, namely the assessment of long-term efficacy and safety endpoints, the study analyses also included data collected in the long-term follow-up study NI-0501-05. Hence these data are reported together. Study NI-0501-05 accepts patients from NI-0501-04 and NI-0501-06. Data collection for the patients from NI-0501-04 is completed.
The primary efficacy and safety analyses are based on the regulatory cut-off date of 20 July 2017. Refer to the publication in N Engl J Med 2020 May 7; 382 (19):1811-1822. Follow-on analyses have been conducted on all patients enrolled in the study, i.e. including the patients enrolled after the cut-off date of 20 July 2017. The results reported here refer to the totality of the 45 patients enrolled.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gender: male and female
- •Age: up to and including 18 years at diagnosis of Haemophagocytic Lymphohistiocytosis
- •Primary HLH patients
- •Patient (if ≥ 18 years old), or patient's legal representative(s) must have signed informed consent
排除标准
- •Diagnosis of secondary Haemophagocytic Lymphohistiocytosis consequent to a proven rheumatic or neoplastic disease.
- •Body weight < 3 kg.
- •Patients treated with biologics within a specific timeframe
- •Active Mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.
- •Presence of malignancy.
- •Concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function
结局指标
主要结局
Overall Response Rate (ORR) Second Line
时间窗: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).
Overall Response Rate (ORR) All Treated
时间窗: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).
Overall Response Rate (ORR) Follow-on Analysis Set:
时间窗: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).
Overall Response Rate (ORR) at End of Treatment in Study NI-0501-04 (EOT 04) Follow-on Analysis Set: All Treated
时间窗: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).
次要结局
- Survival Pre-HSCT(Assessed up to HSCT, whenever HSCT occurred (up to approximately 6 months after treatment initiation))
- Number of Patients Able to Reduce Glucocorticoids(End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks.)
- Time to Response(Assessed up to End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks))
- Durability of First Response(Assessed up to End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks))
- Overall Survival(Time from the date of first dose to last dose, or 8 weeks after first dose.)
- Cumulative Duration of Response(up to start of HSCT conditioning, whenever HSCT conditioning is scheduled (at least 4 weeks after treatment start), or End of Treatment 04/05 (if the patient did not have HSCT performed))
- Survival Post-HSCT(Assessed up to Last Observation (up to 1 year after transplant, or up to approximately 18 months after treatment initiation))