A Randomised, Placebo Controlled, Double Blind, Multicentre Proof of Concept Study to Assess the Safety and Efficacy of Two Doses of VAD044 in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 75
- 试验地点
- 7
- 主要终点
- Part I: Safety and Tolerability
研究概览
简要总结
Part I: The purpose of this Phase 1b proof of concept study, randomised, placebo controlled, double blind, multicentre study is to asssess safety and efficacy of 2 doses of VAD044 in adult HHT patients.
Part II: The purpose of this open-label extension following the completion of the randomised double blind treatment and follow-up period (Part I of the study) is to assess the long-term safetty, tolerability and efficacy of VAD044 in adult HHT patients.
详细描述
Part I: After being informed about the study and the potential risks, all patients giving written informed consent will undergo a two months screening and observation period to determine eligibility for study entry. At Day 0, patients who meet the eligibility requirements will be randomized in a double-blind manner (participant and investigator) in a 1:1:1 ratio to 30mg VAD044 (once daily), 40 mg (once daily) or placebo (once daily).
Part II: Patients who have completed the study Part I can participate in the open-label extension study (Part II).The patients can roll over immediately after last visit of the Part I or at any time at their convenience and according to their availability, but within a timeframe no longer than 8 months after the last visit (visit 12) of the part I. All patients in Part II will receive 30 mg of VAD044 once daily for the first 4 weeks afterwards the daily dose can be increased to 40 mg daily for up to 36 months.
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
- 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
- •For Part I of the study:
- •Inclusion Criteria:
- •Diagnosis of HHT by the Curaçao criteria
- •Several epistaxis/week
- •COVID-19 vaccination or positive COVID-19 antibody test
- •Patient has given written informed consent to participate in Part I
排除标准
- •Type 1 diabetes or uncontrolled type II diabetes (insulin or non-insulin dependent)
- •Active COVID-19 infection
- •active uncontrolled infection or known to be serologically positive for HIV, Hep B, Hep C infection
- •Recent procedures on nasal telangiectases (<6 weeks)
- •Requiring therapeutic anticoagulation
- •Use of drugs with anti-angiogenic properties in the past 8 weeks
- •laboratory abnormalities
- •Fort Part II of the study:
- •Inclusion Criteria:
- •Completion of Part I of the study
- •All adverse events or serious adverse events occuring during Part I of the study have resolved
- •Patient has given written informed consent to participate in Part II
- •Exclusion Criteria:
- •- Same as in Part I.
研究组 & 干预措施
30 mg
30 mg VAD044
干预措施: VAD044 Part I (Drug)
30 mg
30 mg VAD044
干预措施: VAD044 Part II (Drug)
40 mg
40 mg VAD044
干预措施: VAD044 Part I (Drug)
40 mg
40 mg VAD044
干预措施: VAD044 Part II (Drug)
Placebo
Placebo
干预措施: VAD044 Part I (Drug)
结局指标
主要结局
Part I: Safety and Tolerability
时间窗: 12 weeks
Type and severity of Adverse Events (AEs)
Part II: Safety and Tolerability
时间窗: 36 months
Type and severity of Adverse Events (AEs)
次要结局
- Part I: Change in Epistaxis episodes(12 weeks)
- Part I: Change in Epistaxis duration(12 weeks)
- Part I: Change in Epistaxis intensity(12 weeks)
- Part I: Change in Epistaxis Severity Score (ESS)(12 weeks)
- Part I: Change in Haemoglobin(12 weeks)
- Part I: Change Ferritin(12 weeks)
- Part I: Change in blood Transferrin saturation level(12 weeks)
- Part I: Change in Iron supplementation needs(12 weeks)
- Part I: Change Blood tranfusions requirements(12 weeks)
- Part I: Change in the Nasal Outcome for Epistaxis in Hereditary Hemorrhagic Telangiectasia score(12 weeks)
- Part I: Quality of Life Scale SF-12(12 weeks)
- Part I: Plasma concentration of VAD044(12 weeks)
- Part I: Maximum concentration (Cmax) of VAD04(12 weeks)
- Part I: Time of maximum concentration (Tmax) of VAD044(12 weeks)
- Part I: Area under the curve (exposure to drug) during 24 hours (AUC0-24h) of VAD044(12 weeks)
- Part I: Trough concentration (Ctrough) of VAD044(12 weeks)
- Part I: Pharmacodynamics (PD) of VAD044(12 weeks)
- Part II: Change in Epistaxis flow intensity(24 months)
- Part II: Change in The number of Epistaxis episodes(24 months)
- Part II: Change in Epistaxis duration(24 months)
- Part II: Change in Epistaxis Severity Score (ESS)(24 months)
- Part II: Change in Haemoglobin(24 months)
- Part II: Change in Ferritin(24 months)
- Part II: Change in Transferrin saturation level(24 months)
- Part II: Change in Iron supplementation needs(24 months)
- Part II: Change in blood tranfusions requirements(24 months)
- Part II: Quality of Life Scale SF-12(24 months)