Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Trial With Tadekinig Alfa (r-hIL-18BP) 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
- 15
- 试验地点
- 9
- 主要终点
- Prevention of Flares
研究概览
简要总结
This is a Phase 3 study to assess the safety and efficacy of Tadekinig alfa in patients with monogenic, interleukin-18 (IL 18) driven autoinflammation due to Nucleotide-binding oligomerization domain, leucine-rich repeat and caspase recruiting domain (CARD domain) containing 4 (NLRC4) - Macrophage activation syndrome (MAS) mutation (NLRC4-MAS mutation) or X-linked inhibitor of apoptosis (XIAP) deficiency. Because of the likelihood for pathogenic IL-18 in certain monogenic diseases, patients known to harbor deleterious mutations in NLRC4-MAS or XIAP and who have a history of ongoing inflammation will be enrolled if they have ferritin ≥ 500 ng/mL or persistent C reactive protein (CRP) elevation ≥ 2 times the upper limit of normal (ULN) and the patients should have a Modified Autoinflammatory Disease Activity Index (mAIDAI) ≥ 4.
详细描述
The study is designed with single-arm, open-label phase (SAOL) of Tadekinig alfa treatment duration for 18-week followed by an up to 16-week Randomized Withdrawal (RW) period for efficacy and safety evaluation, with no interruption between the two phases of treatment. The screening period will occur before the SAOL phase and before the first dose of Investigational Medicinal Product (IMP)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Tadekinig alfa
Patients that showed response to treatment in the SAOL phase will receive Tadekinig alfa for up to 16 weeks.
干预措施: Tadekinig alfa (Drug)
0.9% sodium chloride
Patients that showed response to treatment in the SAOL phase will receive placebo comparator for up to 16 weeks.
干预措施: 0.9% sodium chloride (Other)
结局指标
主要结局
Prevention of Flares
时间窗: 16 weeks
The primary outcome measure is the time to first occurrence of disease reactivation during the 16-week RW phase. Method of assessment: Biomarkers (CRP / Ferritin) and clinical manifestations of systemic inflammation and end-organ damage.
次要结局
- Improvement in Laboratory Markers - Erythrocyte Sedimentation Rate(18 weeks)
- Hospital Length of Stay(34 weeks)
- Change in Physician Global Assessment (PGA)(34 weeks)
- Local Tolerability at the Injection Site (as Defined by Number of Participants With Adverse Events of Special Interest)(34 weeks (SAOL + RW phases))
- Best Response(18 weeks)
- Improvement in Laboratory Markers - Hemoglobin(18 weeks)
- Improvement in Laboratory Markers - Fibrinogen(18 weeks)
- Improvement in Laboratory Markers - D-Dimer(18 weeks)
- Immunogenicity Evaluation(34 weeks (SAOL + RW phases))
- Duration of Response During the SAOL Phase (Until End of Phase or Disease Reactivation)(The actual mean treatment duration in the SAOL phase was 17.6 weeks (minimum / maximum 5.9 / 22.1 weeks).)
- Change From Baseline in mAIDAI Total Score in the SAOL Phase(18 weeks)
- Change From Baseline in Serum Ferritin(34 weeks)
- Change From Baseline in Serum CRP(34 weeks)
- Improvement in Laboratory Markers - Albumin(18 weeks)
- Disease Reactivation Rate(18 weeks)
- Treatment Failures(18 weeks)
- Resolution of Fevers, Hepato/Splenomegaly and Skin Rash(18 weeks)
- Improvement in Laboratory Markers - AST (SGOT)(18 weeks)
- Improvement in Laboratory Markers - ALT (SGPT)(18 weeks)
- Improvement in Laboratory Markers - Platelets(18 weeks)
- Change in Patient/Caregiver Qualitative Evaluation of Health Status in Randomized Withdrawal Phase(16 weeks)