Open-label Extension Study with Tadekinig Alfa (r-hIL-18BP) to Monitor Safety and Tolerability in Patients with IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 11
- 主要终点
- Reports of abnormal laboratory results
研究概览
简要总结
This is an open-label extension study for patients previously enrolled in the AB2 Bio Ltd. ongoing Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953). This OLE study will evaluate the long-term safety and tolerability of Tadekinig alfa in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP.
详细描述
Pediatric auto-inflammatory conditions related to spontaneous activating mutations of the NLRC4 and with recurrent MAS-like flares with constitutive IL-18 hypersecretion, may require long-term blockade of the IL-18 pathway.
Patients with X-linked inhibitor of apoptosis (XIAP) deficiency and suffering from Hemophagocytic-Lymphohistiocytosis (HLH), a MAS-like syndrome, also show high levels of serum IL-18 and may benefit from IL-18 blockade treatment until a curative hematopoietic stem cell transplantation can be performed The safety of IL-18 blockade during long-term periods is of major interest for the treatment of these patients
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(both criteria must be met)
- •Patients have participated in AB2 Bio ltd. Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) by one of the following mechanisms : a) Patients that have completed the first 18-week RCT phase of the preceding clinical trial but were not eligible for the RW phase due to flare symptoms. Or b) Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial. Or c) Patients who have exited either the RCT or RW phase of the preceding clinical trial due to treatment failure requiring rescue immunosuppression. Such patients must wait a minimum of 4 weeks after treatment discontinuation from the preceding clinical trial before enrolling in this OLE. If patients do not consent to enroll in the OLE after their early termination in the main study, they will be asked to continue with the planned visits of the main study
- •Women of childbearing potential with negative urine pregnancy test (UPT) at all visits
排除标准
- •Patients may not enter the OLE if they voluntarily withdrew from RCT or RW study or if the time period between participation exceeds 3 months
- •Evidence or history of malignancy
- •Evidence of invasive or life-threatening infection
- •History of tuberculosis
- •Life-threatening bleeding within 2 weeks of screening
- •Vaccination with a live vaccine within the previous 3 months
- •Evidence of severe organ compromise including but not limited to: (see details in the protocol)
- •Pregnant or breastfeeding females
- •Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment.
- •Inability to provide informed consent, and also assent if applicable
- •Life expectancy less than 4 weeks
- •Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
研究组 & 干预措施
Tadekinig alfa
Active drug treatment during 26 weeks
干预措施: Tadekinig alfa (Drug)
结局指标
主要结局
Reports of abnormal laboratory results
时间窗: 26 weeks
Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results
Immunogenicity evaluation
时间窗: 26 weeks
Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
Evaluation of the local tolerability at the injection site
时间窗: 26 weeks
Evaluation will be done based on the Local Tolerability Index where the patients will be asked to assess the degree of pain, redness, swelling, bruising, tenderness and itching, they are experiencing from each injection.
Reports of adverse events
时间窗: 26 weeks
The incidence, nature and severity of AEs will be reported
Reports of abnormal physical examination
时间窗: 26 weeks
Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0.
次要结局
未报告次要终点