A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant Extended-release (XR) Tablet for Prophylaxis and Deucrictibant Immediate-release (IR) Capsule for On-demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency
概览
- 阶段
- 3 期
- 干预措施
- Deucrictibant
- 疾病 / 适应症
- 未指定
- 发起方
- Pharvaris Netherlands B.V.
- 入组人数
- 32
- 试验地点
- 7
- 主要终点
- Part 1 (Prophylaxis, Double-blind Treatment Phase)
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
This is a Phase 3, multicenter, 3-part study, with 2 randomized, double-blind, placebo-controlled parts and an open-label extension part, to evaluate the efficacy and safety of orally administered deucrictibant XR tablet for prophylaxis, and deucrictibant IR capsule for on-demand treatment of angioedema attacks in adult participants aged ≥ 18 years with AAE-C1INH.
详细描述
The study consists of a Screening Period, during which eligibility is confirmed, a Part 1 Prophylaxis Double-blind Treatment Phase, a Part 2 On-demand, Double-blind Treatment Phase, and a Part 3 On-demand Open-label Extension Phase. Approximately 24 participants will be randomized in Part 1 into 2 parallel arms for a treatment period of 12 weeks. During the prophylaxis treatment period participants will receive blinded study drug (deucrictibant 40 mg XR or placebo randomized in a 1:1 ratio). Upon completion of Part 1, participants will roll-over into Part 2. In addition to rollover participants completing Part 1, new deucrictibant treatment-naïve participants will be enrolled directly into Part 2 and this may occur while Part 1 is ongoing. During the on-demand period participants will receive blinded study drug (deucrictibant 20 mg IR capsule or matching placebo randomized in a 1:1 ratio, 2-period, 2-treatment crossover design) for 2 qualifying AAE-C1INH attacks. Participants completing Part 2 may roll over into Part 3 where all AAE-C1INH attacks will be treated with open-label deucrictibant 20 mg soft capsule.
研究者
入排标准
入选标准
- •Provision of written informed consent
- •Male or female (sex at birth) aged ≥18 years
- •Diagnosis of AAE-C1INH
- •History of AAE-C1INH attacks prior to the Screening Visit:
- •Participants enrolling in Part 1 must have stable underlying disease of AAE-C1INH
- •The underlying condition can reasonably be expected to remain stable for the duration
- •Reliable access and ability to use available therapy to effectively manage AAE- C1INH attacks.
- •Female participants of childbearing potential must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method.
- •Females of non-childbearing potential (prepubertal, surgically sterile, or postmenopausal with ≥ 12 months amenorrhea and postmenopausal FSH confirmation) are not required to use contraception during the study.
- •Capable of recording, without assistance, eDiary and ePRO data using an electronic device, as evidenced by the eDiary and ePRO training.
排除标准
- •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 the Screening Visit (whichever is longer).
- •Participants who have previously received prophylactic therapy but have stopped can participate in this study provided the last dose of the treatment was received prior to the timepoint before the Screening Visit
- •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 epilepsy and/or other significant neurological diseases
- •Any clinically significant and uncontrolled gastrointestinal dysfunction that may impact study drug absorption
- •Evidence of current alcohol or drug abuse
- •Use of medications that are moderate and strong inhibitors of cytochrome P450 (CYP) 3A4, or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) at the time of the Screening Visit
研究组 & 干预措施
Part 2 - Arm 1
干预措施: Deucrictibant
Part 2 - Arm 1
干预措施: Placebo
Part 2 - Arm 2
干预措施: Deucrictibant
Part 2 - Arm 2
干预措施: Placebo
Part 1 - Arm 1 - Active
干预措施: Deucrictibant
Part 1 - Arm 2 - Placebo
干预措施: Placebo
Part 3 - Open-label
干预措施: Deucrictibant
结局指标
主要结局
Part 1 (Prophylaxis, Double-blind Treatment Phase)
时间窗: 12 weeks
Time-normalized number of Investigator-confirmed AAE attacks during Treatment Phase
Part 2 (On-demand, Double-blind Treatment Phase)
时间窗: 12 hours post-treatment
Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"
Part 3 (On-demand, Open-label Extension Treatment Phase)
时间窗: Through study completion, an average of 36 weeks
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
次要结局
- Part 1 (Prophylaxis, Double-blind Treatment Phase)(From enrollment through end of Part 1 (Week 12))
- Part 2 (On-demand, Double-blind Treatment Phase)(Day 1)
- Part 1 (Prophylaxis, Double-blind Treatment Phase)(12 weeks)
- Part 2 (On-demand, Double-blind Treatment Phase)(sustained within 24 hours post-treatment)
- Part 2 (On-demand, Double-blind Treatment Phase)(12 hours post-treatment)
- Part 2 (On-demand, Double-blind Treatment Phase)(12 weeks)