A Phase 1 Trial of TER-1754 in Patients With Hereditary Hemorrhagic Telangiectasia
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Phase 1a: Safety and Tolerability of TER-1754
研究概览
简要总结
This is a Phase 1a/1b, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of TER-1754 (a novel AKT1 inhibitor) in patients with HHT.
详细描述
This is a first-in-human, Phase 1, multicenter trial that includes two parts:
- Phase 1a (dose escalation) will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of TER-1754 in patients with HHT and determine the maximum tolerated or administered dose.
- Phase 1b (proof of concept) will evaluate clinical activity and further characterize the safety profile of TER-1754 in patients with HHT. The Phase 1b treatment period is separated into a blinded treatment segment followed by an open-label extension (OLE) segment.
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
- None
盲法说明
Phase 1a is open label, dose escalation. The Phase 1b treatment period is separated into a blinded treatment segment followed by an open-label extension (OLE) segment
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
- •Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
- •A clinical diagnosis of HHT as defined by the Curaçao criteria
- •Baseline (1-month) ESS ≥ 4
- •Anemia or parental iron infusion of at least 500 mg or transfusion of at least 2 units of RBCs within the preceding 24 weeks.
- •Adequate bone marrow function
- •Adequate renal function
- •Adequate hepatic function
排除标准
- •Prior nonresponse or loss of response to an agent that inhibits AKT1 and/or AKT2 as the primary mechanism of action.
- •Diagnosis of DM requiring insulin treatment
- •Known significant bleeding sources other than nasal, GI, or menstrual/ uterine
- •Known underlying hypoproliferative anemia or clinically significant hemolytic anemia
研究组 & 干预措施
Phase 1a (Dose Escalation) TER-1754 dose escalation
TER-1754 Oral tablets
干预措施: TER-1754 (Drug)
Phase 1b (Proof of Concept)
Placebo oral tablets
干预措施: Placebo (Drug)
Phase 1b (Proof of Concept) - Phase 1b TER-1754 lower dose to begin post determination in Phase 1a
Patient will receive one of the two doses determined post Phase 1a
干预措施: TER-1754 (Drug)
Phase 1b (Proof of Concept) - Phase 1b TER-1754 higher dose to begin post determination in Phase 1a.
Patient will receive one of the two doses determined post Phase 1a
干预措施: TER-1754 (Drug)
结局指标
主要结局
Phase 1a: Safety and Tolerability of TER-1754
时间窗: up to 48 weeks
Incidence of adverse events characterized by type, seriousness, relationship to study treatment, and severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Phase 1a: Maximum Tolerated Dose (MTD) and/or Maximum Administrated Dose (MAD) of TER-1754
时间窗: 28 days
Incidence dose-limiting toxicities (DLTs) characterized by type, seriousness, and severity according to NCI CTCAE v5.0 (dose escalation only).
Phase 1b - Evaluate the Change from baseline in epistaxis and symptom-related clinical activity scores at Week 24
时间窗: 48 weeks
Assess change from baseline in epistaxis duration
次要结局
- Phase 1a and 1b: Evaluate TER-1754 Peak Plasma Concentration (Cmax)(up to 48 weeks)
- Phase 1a and 1b: Evaluate change from baseline in Daily Epistaxis (EQ) Questionnaire(up to 48 weeks)
- Phase 1a and 1b: Evaluate HHT-specfic quality of life(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 Time to Peak Concentration (Tmax)(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 Area Under the Concentration-Time Curve (AUC0-last)(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 AUC0-24(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 AUC∞(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 Terminal Half-Life (t½)(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 Accumulation Ratio at Steady State(Up to 48 weeks)
- Phase 1a and 1b: Evaluate TER-1754 Mean Residence Time (MRT)(Up to 48 weeks)
- Phase 1a and 1b: Change from baseline in Nasal Obstruction Symptom Evaluation Score for HHT (NOSE HHT)(up to 48 weeks)