An Adaptive Dose Escalation and Expansion Basket Trial to Explore the Safety, Pharmacology, and Clinical Activity of TGD001 in Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP) and Other Thrombotic Microangiopathies
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 70
- 主要终点
- Incidence of treatment emergent adverse events (safety and tolerability of TGD001)
研究概览
简要总结
This is a Phase 1/2, prospective, adaptive design trial of TGD001 in participants with suspicion or clinical diagnosis of acute immune thrombotic thrombocytopenic purpura (iTTP) episodes and participants with suspicion or clinical diagnosis of an acute Thrombotic Microangiopathy (TMA) episode. The trial is an open-label, dose escalation and expansion basket trial.
详细描述
In Part A, dose escalation of TGD001 is conducted in participants with suspicion or clinical diagnosis of immune thrombotic thrombocytopenic purpura (iTTP) in conjunction with their respective standard of care to identify a tolerated dose(s) with a pharmacological/clinical response to be evaluated in Part B.
Once a recommended dose of TGD001 is established in Part A, the dose expansion/basket part of the trial will commence. In Part B, "basket" cohorts of participants with iTTP and other Thrombotic Microangiopathies (TMAs) will receive single or repeat doses of TGD001 in conjunction with their respective standard of care to determine the TGD001 dose and treatment regimen with clinical effect in reducing the initial thrombus burden.
Baskets will include up to 20 participants each and may be combined based on emerging safety and efficacy findings. Baskets may be further expanded with the TGD001 dose(s) and regimen(s) that displayed the best clinical response as assessed by the Data Safety Management Committee up to a total of approximately 60 participants in Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •18 years old or older
- •Willing to sign an informed consent form
- •Willing to refrain from sexual intercourse or must use a contraceptive method that is highly effective for 90 days after the last dose of TGD001
- •Symptomatic acute TMA episode
- •Accessible to follow-up
排除标准
- •Diagnosis other than TMA, which could account for the findings of thrombocytopenia and hemolytic anemia
- •Diagnosis of Shiga-toxin induced HUS
- •Known bone marrow/graft failure
- •Diagnosis of ongoing severe, uncontrolled Graft versus Host Disease
- •Received therapeutic plasma exchange (PEX) within 7 days prior to screening
- •Use of an anticoagulant and/or thrombolytics
- •Active internal bleeding
- •Any major bleeding episode within the past 30 days, or diagnosis of chronic bleeding conditions
- •Known gastrointestinal ulcer
- •Severe, uncontrolled hypertension, renal impairment requiring dialysis, or liver impairment, or active infection indicated by sepsis
- •Life expectancy less than 3 months independent of TMA disorder
- •Pregnant or breastfeeding
研究组 & 干预措施
Dose Level 1
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
Dose Level 2
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
Dose Level 3
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
Dose Level 4
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
Basket 1
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
Basket 2
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
Basket 3
TGD001 IV bolus administration
干预措施: TGD001 (Drug)
结局指标
主要结局
Incidence of treatment emergent adverse events (safety and tolerability of TGD001)
时间窗: 90 days
Measurement of treatment emergent adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) criteria
次要结局
- Change from baseline in lactate dehydrogenase (LDH) and other tissue damage markers(90 days)
- Change from baseline in platelet count(90 days)
- Time to resolution of the thrombotic episode(90 days)
- Change from baseline of disease-related signs and symptoms using CTCAE v5.0 criteria(90 days)
- Duration of ICU stay and hospitalization(90 days)
- Occurrence of all-cause and disease-specific mortality(90 days)
- Peak plasma concentration (Cmax) of TGD001(90 days)
- Area under the plasma concentration versus time curve (AUC) of TGD001(90 days)
- Time to maximum TGD001 plasma concentration(90 days)
- Plasma half-life (t1/2) of TGD001(90 days)
- Number of participants with ADA(90 days)