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口服 PHA-022121 预防 I 型或 II 型遗传性血管性水肿患者血管性水肿发作的剂量范围研究 (HAE CHAPTER-1)

2026年8月12日 更新者：Pharvaris Netherlands B.V.

一项 II 期、双盲、安慰剂对照、随机、剂量范围、平行组研究，以评估口服 PHA-022121 预防因 C1 抑制剂缺乏引起的遗传性血管性水肿患者血管性水肿发作的安全性和有效性（ I 型或 II 型）

本研究评估口服 PHA-022121 预防遗传性血管性水肿 (HAE) 患者血管性水肿发作的安全性和有效性。 该研究由 2 部分组成，患者在第 2 部分开始治疗之前完成第 1 部分的参与。该研究的第 1 部分有 3 个平行组，大约 30 名患者将平均随机分配到 PHA-022121 的两种剂量方案之一或匹配的安慰剂。 完成第 1 部分后，患者将继续参加研究第 2 部分中的单个开放标签组。 筛选期长达 8 周，治疗期为 12 周（第 1 部分）和 50 周（第 2 部分）。

研究概览

地位

终止

条件

干预/治疗

研究类型

介入性

注册 (实际的)

34

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 保加利亚
      • Sofia、保加利亚、1680
        • Study Site
  • 加拿大
    • Ontario
      • Ottawa、Ontario、加拿大、K1H 1E4
        • Study Site
    • Quebec
      • Montreal、Quebec、加拿大、H2W 1R7
        • Study Site
  • 奥地利
      • Vienna、奥地利、A-1090
        • Study Site
  • 德国
      • Berlin、德国、10117
        • Study Site
      • Frankfurt、德国、60323
        • Study Site
  • 意大利
      • Milan、意大利、20157
        • Study Site
      • Palermo、意大利、0146
        • Study Site
    • PD
      • Padua、PD、意大利、35128
        • Study Site
  • 波兰
      • Krakow、波兰
        • Study Site
  • 爱尔兰
      • Dublin、爱尔兰、D08NHY1
        • Study Site
  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35209
        • Study Site
    • Arizona
      • Paradise Valley、Arizona、美国、85253
        • Study Site
    • Missouri
      • St Louis、Missouri、美国、63141
        • Study Site
  • 英国
    • England
      • Brighton、England、英国、BN2 1ES
        • Study Site
      • Bristol、England、英国、BS10 5NB
        • Study Site
      • Cambridge、England、英国、CB2 0QQ
        • Study Site
      • London、England、英国、E1 1FR
        • Study Site
      • Southampton、England、英国、SO16 6YD
        • Study Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 75年 (成人、年长者)

接受健康志愿者

不

描述

纳入标准：

  • 签署并注明日期的知情同意书
  • I 型或 II 型 HAE 的诊断
  • 在筛选前的最后连续 3 个月内记录至少 3 次 HAE 发作，或在筛选期间至少 2 次 HAE 发作
  • 使用标准急性发作药物的可靠途径和经验

排除标准：

  • 怀孕或哺乳
  • 有临床意义的异常心电图
  • 会影响患者安全或参与研究能力的任何其他全身性疾病或重大疾病或病症
  • 在入组前的规定时间内使用 C1 酯酶抑制剂、口服激肽释放酶抑制剂、减毒雄激素、抗纤维蛋白溶解药或单克隆 HAE 治疗
  • 肝功能异常
  • 肾功能异常
  • 在特定时期内有酗酒或吸毒史，或目前有物质依赖或滥用的证据
  • 在规定的期限内参与任何其他研究性药物研究

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：预防
  • 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
安慰剂比较：第 1 部分：安慰剂
BID 安慰剂
药品：安慰剂
匹配的口服安慰剂胶囊
实验性的：第 1 部分：低剂量
BID 低剂量减毒剂
药品：减毒剂低剂量
口服减毒剂软胶囊（PHVS416）
实验性的：第 1 部分：高剂量
BID 高剂量减毒剂
药品：减毒剂大剂量
口服减毒剂软胶囊（PHVS416）
实验性的：第 2 部分：开放标签
BID 高剂量减毒剂
药品：减毒剂大剂量
口服减毒剂软胶囊（PHVS416）

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
Number of Investigator-confirmed Hereditary Angioedema (HAE) Attacks (Expressed as the Normalized Number of Attacks Per Month [4 Weeks] of Exposure) During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily electronic patient-reported outcome (ePRO) diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Mean rate ratio, confidence interval (CI), and p-value were estimated using a generalized linear model with Poisson distribution, with baseline attack rate included as a factor.
Up to Day 84

次要结果测量

结果测量
措施说明
大体时间
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days×28. Moderate HAE attack defined as which limits/interferes with the participant's ability to attend work/school or participate in family life and social/recreational activities whereas Severe HAE attack significantly limits the participant's ability.
Up to Day 84
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
Up to Day 84
Number of Participants Achieving ≥50%, ≥70% and ≥90% Reduction in Attack Rate Relative to Baseline During the Treatment Period in Part 1
大体时间：Up to Day 84
Baseline attack rate was defined as each participant's normalized HAE attack rate (attacks per 4 weeks) prior to randomization, based on documented history or confirmed during screening. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Percent reduction from baseline was calculated for each participant by comparing the normalized treatment-period attack rate to the baseline attack rate. Participants were classified as responders if they achieved ≥50%, ≥70%, or ≥90% reduction in attack rate relative to baseline during Part 1.
Up to Day 84
Number of Participants Who Were Investigator-confirmed Attack-free During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Participants reporting no confirmed attacks over the treatment period were considered attack-free.
Up to Day 84
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Up to Day 84
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Up to Day 84
Time to First Investigator-confirmed HAE Attack in the Treatment Period in Part 1
大体时间：Up to Day 84
Time to first investigator-confirmed HAE attack was defined as days from date of first administration of study drug until the onset date of first Investigator-confirmed HAE attack. Participants without an Investigator-confirmed HAE attack during the treatment period in Part 1 were censored at the date of the last dose of study drug +1 in Part 1 or last day of the study, whichever came sooner.
Up to Day 84
Number of Investigator-confirmed HAE Attacks Resulting in a Visit to the Emergency Department or an Admission to Hospital During the Treatment Period in Part 1
大体时间：Up to Day 84
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Only Investigator-confirmed attacks resulting in emergency department visits or hospital admissions were included.
Up to Day 84
Number of Investigator-confirmed HAE Attacks During the Treatment Period in Part 2
大体时间：Day 84 to Day 938
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. An attack will be counted as in Part 2 if it occurs after the first IMP administration in Part 2 and within 24 hours after last IMP administration in Part 2.
Day 84 to Day 938
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 2
大体时间：Day 84 to Day 938
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days×28. Moderate HAE attack defined as which limits/interferes with the participant's ability to attend work/school or participate in family life and social/recreational activities whereas Severe HAE attack significantly limits the participant's ability. LSM and SE were estimated using a generalized linear model with Poisson distribution.
Day 84 to Day 938
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 2
大体时间：Day 84 to Day 938
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. LSM and SE were estimated using a generalized linear model with Poisson distribution.
Day 84 to Day 938
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2
大体时间：Day 84 to Day 938
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Day 84 to Day 938
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2
大体时间：Day 84 to Day 938
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Day 84 to Day 938

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Pharvaris Netherlands B.V.

调查人员

  • 首席研究员：Marc Riedl, MD、UC San Diego, La Jolla, California, United States
  • 首席研究员：Emel Aygören-Pürsün, MD、University Hospital Frankfurt - Goethe University, Frankfurt, Germany

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年4月19日

初级完成 (实际的)

2025年6月30日

研究完成 (实际的)

2025年6月30日

研究注册日期

首次提交

2021年9月7日

首先提交符合 QC 标准的

2021年9月7日

首次发布 (实际的)

2021年9月17日

研究记录更新

最后更新发布 (实际的)

2026年8月17日

上次提交的符合 QC 标准的更新

2026年8月12日

最后验证

2026年8月1日

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

  • PHA022121-C301
  • 2021-000227-13 (EudraCT编号)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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