A Long-term, Open-label Study to Evaluate the Safety and Efficacy of Orally Administered Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 170
- 试验地点
- 68
- 主要终点
- Number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
研究概览
简要总结
This is a Phase 3, multicenter, long-term, open-label study to evaluate the safety and efficacy of once-daily orally administered deucrictibant extended-release tablet for prophylaxis to prevent angioedema attacks in participants aged ≥12 years with Hereditary Angioedema
详细描述
The study consists of a Screening Period during which eligibility is confirmed (only for participants not rolling over within 28 days from a previous deucrictibant prophylactic study), a Treatment Period in which participants will receive open-label deucrictibant extended-release tablet once daily for approximately 240 weeks, followed by an End of Study visit after maximum 4 weeks. Participants will undergo regular safety (e.g. lab draws) and efficacy assessments, will complete an electronic diary, and also complete questionnaires at predefined timepoints during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of the signed ICF by the participant and/or legally designated representative.
- •Male or female, aged ≥12 years at the time of providing written informed consent/assent.
- •Diagnosis of hereditary angioedema (HAE)
- •For participants that did not participate in a previous deucrictibant prophylactic study: history of at least 1 attack in the last 3 consecutive months prior to Screening
- •Reliable access and ability to use standard of care on-demand treatments to effectively manage acute HAE attacks.
- •Willing and able to adhere to all protocol requirements, including the participant being capable of and compliant with data recording into an eDiary.
- •Female participants of childbearing age must agree to the protocol specified pregnancy testing and contraception methods.
排除标准
- •Any diagnosis of angioedema other than HAE
- •Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at ICF signature (whichever is longer)
- •Prior gene therapy for any indication at any time
- •Participants who discontinued from previous studies with deucrictibant prophylactic and/or on-demand treatment due to safety reasons or compliance issues that, in the opinion of the Investigator, would interfere with the participant's safety or compliance to participate in the study
- •Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks of Screening
- •Use of prophylactic treatment for HAE within 2 weeks of Screening for C1INH, oral kallikrein inhibitors, or anti-fibrinolytics; within 4 weeks of Screening for attenuated androgens; within 5 half-lives of Screening for monoclonal antibodies, or within 7 days of Screening for short-term prophylaxis
- •Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
- •Abnormal hepatic function
- •Moderate or severe renal impairment
- •Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
- •History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse
- •Use of medications that are moderate and strong inhibitors or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) of the time of enrollment.
- •Known hypersensitivity to deucrictibant or any of the excipients of the study drug
研究组 & 干预措施
Deucrictibant
Deucrictibant
干预措施: Deucrictibant (Drug)
结局指标
主要结局
Number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
时间窗: Up to Week 240
Change in heart rate
时间窗: Up to Week 240
Change in blood pressure
时间窗: Up to Week 240
Change in body temperature
时间窗: Up to Week 240
Number of participants with clinically significant changes in Hematology
时间窗: Up to Week 240
Blood samples will be collected for the analysis of hematology parameters.
Number of participants with clinically significant changes in Clinical Chemistry
时间窗: Up to Week 240
Blood samples will be collected for the analysis of clinical chemistry parameters.
Number of participants with clinically significant changes in Urinalysis
时间窗: Up to Week 240
Urine samples will be collected for the analysis of urinalysis parameters.
Change from Baseline electrocardiograms (ECGs)
时间窗: Up to Week 240
Digital triplicate 12-lead ECG. Descriptive in nature, no formal statistical hypothesis testing will be performed.
次要结局
- Time-normalized number of Investigator-confirmed HAE attacks during the Treatment Period(Up to Week 240)
- Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the Treatment Period(Up to Week 240)
- Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during Treatment Period(Up to Week 240)
- Time-normalized number of Investigator-confirmed severe HAE attacks during the Treatment Period(Up to Week 240)
- Proportion of time without angioedema symptoms during the Treatment Period(Up to Week 240)
- Patient reported outcome: Angioedema Quality of Life (AE-QoL) questionnaire(Up to Week 132)
- Patient reported outcome: Patient Global Assessment of Change (PGA-Change)(Up to Week 132)
- Patient reported outcome: Angioedema Control Test 4-week version (AECT-4wk)(Up to Week 132)
- Patient reported outcome: Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)(Up to Week 132)
- Patient reported outcome: Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)(Up to Week 132)
- Pharmacokinetics [PK]: Pre-dose plasma concentration of deucrictibant and deucrictibant metabolites (Ctrough)(Up to Week 96)
- Pharmacokinetics [PK]: Urine concentration of deucrictibant and deucrictibant metabolites(Up to Week 48)