Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
A Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept Study of ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
This is a 2-part study evaluating ATV-1601 in participants with moderate to severe HHT. Part 1 is a randomized, double-blind, placebo-controlled study evaluating 3 dosing regimens of ATV-1601. Patients completing Part 1 may participate in the Part 2 open-label extension to receive ATV-1601.
研究概览
详细说明
Part 1: This is a Phase 1/2 proof-of-concept, double-blind, multicenter, placebo-controlled study to evaluate the safety, pharmacokinetics and efficacy of 3 oral dosing regimens of ATV-1601. Participants who meet eligibility requirements will be randomized in a double-blind manner to one of 3 doses of ATV-1601 or placebo. Participants will receive double-blind study treatment for a 16-week period.
Part 2: Eligible participants who complete Part 1 may enroll in an open-label extension study to receive up to 2 years of additional treatment. All participants in the open-label extension will receive ATV-1601. Once the recommended Phase 2 dose (RP2D) is determined based on Part 1, all participants in Part 2 will have the option to switch to the RP2D.
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Arizona
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Phoenix、Arizona、美国、85013
- 招聘中
- Arizona Pulmonary Specialists
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接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
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Georgia
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Augusta、Georgia、美国、30912
- 招聘中
- Augusta University Medical Center
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接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
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Indiana
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Indianapolis、Indiana、美国、46260
- 招聘中
- Innovative Hematology
-
接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
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Massachusetts
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Boston、Massachusetts、美国、02114
- 招聘中
- Massachusetts General Hospital
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接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
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Minnesota
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Rochester、Minnesota、美国、55905
- 招聘中
- Mayo Clinic
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接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
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Missouri
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St Louis、Missouri、美国、63110
- 招聘中
- Washington University in St. Louis
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接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
-
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North Carolina
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Chapel Hill、North Carolina、美国、27599
- 招聘中
- University of North Carolina
-
接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
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Utah
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Salt Lake City、Utah、美国、84132
- 招聘中
- University of Utah Health Sciences Center
-
接触：
- Study Director Atavistik
- 电话号码：857-285-5400
- 邮箱：studydirector@atavistikbio.com
-
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Ability to provide informed consent prior to any study-specific procedures
- Confirmed diagnosis of hereditary hemorrhagic telangiectasia (HHT) based on Curaçao criteria
- Moderate to severe HHT with an ESS ≥ 4
- Anemia at Screening and/or requirement for at least 1 red-cell unit (RUE) in the previous 6 months
- Adequate hematologic, renal, and hepatic function per protocol-defined laboratory criteria
- Use highly effective contraception during the study and for a protocol-defined period after last dose
Exclusion Criteria:
- Clinically significant abnormalities of glucose metabolism including diagnosed Type 1 or uncontrolled Type 2 diabetes
- Chronic cardiac disease, or cardiac rhythm abnormalities
- History of significant cardiovascular, hepatic, renal, or hematologic disease not related to HHT that may confound study results
- Use of prohibited concomitant medications within a protocol-defined washout period prior to first dose (including strong CYP modulators and certain herbal supplements)
- Recent (within 6 weeks) major surgery or local ablative procedures, or procedures on nasal telangiectasias
- Prior AKT inhibitor
- Pregnant or breastfeeding women
Additional Criteria for Open-Label Extension:
- Participants must complete the double-blind treatment period (Part 1)
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Part 1: 60 mg QD
Active drug, once daily |
Administered orally, daily
其他名称：
|
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实验性的：Part 1: 100 mg QD
Active drug, once daily |
Administered orally, daily
其他名称：
|
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实验性的：Part 1: 60 BID
Active drug, twice daily |
Administered orally, daily
其他名称：
|
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实验性的：Part 1: Placebo
Control Arm |
Administered orally, daily
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Part 1: Safety and tolerability
大体时间：16 weeks
|
Number and severity of treatment-emergent adverse events (TEAEs) and study drug-related TEAEs |
16 weeks
|
|
Part 2: Safety and tolerability
大体时间：24 months
|
Type, incidence, severity, timing, seriousness and relatedness of AEs and laboratory abnormalities |
24 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Part 1: Change in Epistaxis duration
大体时间：16 weeks
|
28-day total duration compared to baseline |
16 weeks
|
|
Part 1: Epistaxis frequency
大体时间：16 weeks
|
28-day frequency of nosebleeds compared to baseline |
16 weeks
|
|
Part 1: Epistaxis intensity
大体时间：16 weeks
|
28-day average epistaxis intensity (6-point scale) of nosebleeds compared to baseline |
16 weeks
|
|
Part 1: Intensity-weighted epistaxis duration
大体时间：16 weeks
|
28-day intensity-weighted duration of nosebleeds |
16 weeks
|
|
Part 1: Epistaxis Severity Score (ESS)
大体时间：16 weeks
|
The Epistaxis Severity Score (ESS) is a validated 6-question instrument with scores ranging from 0 to 10, where higher scores indicate more severe epistaxis symptoms. |
16 weeks
|
|
Part 1: Change in Hemoglobin
大体时间：16 weeks
|
Hemoglobin levels compared to baseline |
16 weeks
|
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Part 1: Change in Parenteral iron use
大体时间：16 weeks
|
Amount of parenteral iron administered compared to 16-weeks prior to treatment initiation |
16 weeks
|
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Part 1: Change in Blood transfusion requirements
大体时间：16 Weeks
|
Amount of packed red blood cell (PRBC) transfusions and rate of transfusion independence compared to 16-weeks prior to treatment initiation |
16 Weeks
|
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Part 1: Pharmacokinetics - Maximum observed concentration (Cmax)
大体时间：16 Weeks
|
Maximum plasma concentration |
16 Weeks
|
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Part 1: Pharmacokinetics - Area under the concentration-time curve over the dosing interval (AUCtau)
大体时间：16 Weeks
|
Systemic exposure of ATV-1601 over the dosing interval |
16 Weeks
|
|
Part 1: Pharmacokinetics - Area under the concentration-time curve extrapolated to infinity (AUCinf)
大体时间：16 Weeks
|
Total systemic exposure of ATV-1601 extrapolated to infinite time |
16 Weeks
|
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Part 1: Pharmacokinetics - Time to maximum concentration (Tmax)
大体时间：16 Weeks
|
Time to reach maximum plasma concentration |
16 Weeks
|
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Part 1: Pharmacokinetics - minimum concentration (Cmin)
大体时间：16 Weeks
|
Pre-dose trough plasma concentration |
16 Weeks
|
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Part 1: Pharmacokinetics - Half-life (t½)
大体时间：16 Weeks
|
Time required for plasma concentration to decrease by half |
16 Weeks
|
|
Part 2: Epistaxis duration
大体时间：Up to 2 years
|
28-day total duration every 4 weeks |
Up to 2 years
|
|
Part 2: Epistaxis frequency
大体时间：Up to 2 years
|
Total number of nosebleeds every 4 weeks |
Up to 2 years
|
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Part 2: Epistaxis Severity Score (ESS)
大体时间：At 12 weeks and every 12 weeks thereafter up to study completion
|
Severity of nosebleeds using a score of 0-10 automatically calculated based on responses to 6 questions. |
At 12 weeks and every 12 weeks thereafter up to study completion
|
|
Part 2: Change in Hemoglobin
大体时间：Monthly during Part 2
|
Hemoglobin levels compared to baseline |
Monthly during Part 2
|
|
Part 2: Parenteral iron use
大体时间：At 12 weeks and every 12 weeks thereafter up to study completion
|
Total amount of parenteral iron infused (mg) compared to baseline (12 weeks prior to treatment initiation |
At 12 weeks and every 12 weeks thereafter up to study completion
|
|
Part 2: Blood transfusion requirements
大体时间：At 12 weeks and every 12 weeks thereafter during part 2
|
Total number of packed red blood cell (PRBC) transfusions (units) compared to baseline |
At 12 weeks and every 12 weeks thereafter during part 2
|
|
Part 2: Transfusion independence
大体时间：At 12 weeks and every 12 weeks thereafter during part 2
|
Proportion of participants who do not require PRBC transfusions |
At 12 weeks and every 12 weeks thereafter during part 2
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- ATV-1601-102
- Harmony-HHT (其他标识符：Atavistik Bio Inc)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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