A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 32
- 主要终点
- Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase
研究概览
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 soft 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 soft 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
- •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.
- •If underlying disease associated with AAE is present, the underlying disease must be stable throughout the duration of part
- •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 (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).
- •Receiving long-term prophylaxis (LTP) treatment for AAE-C1INH and satisfied with this treatment. Participants who are not satisfied (eg, tolerability issues, lack of efficacy) and have previously stopped LTP treatment for AAE-C1INH, for reasons other than participation in this study, can sign the ICF and begin the Screening Period only if their 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
- •Known hypersensitivity to deucrictibant or any of the excipients of the study drug
- •Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit
研究组 & 干预措施
Part 2 - Arm 2
干预措施: Placebo (Drug)
Part 1 - Arm 2 - Placebo
干预措施: Placebo (Drug)
Part 2 - Arm 1
干预措施: Placebo (Drug)
Part 2 - Arm 2
干预措施: Deucrictibant (Drug)
Part 3 - Open-label
干预措施: Deucrictibant (Drug)
Part 1 - Arm 1 - Active
干预措施: Deucrictibant (Drug)
Part 2 - Arm 1
干预措施: Deucrictibant (Drug)
结局指标
主要结局
Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase
时间窗: 12 weeks
Part 2: Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"
时间窗: 12 hours post-treatment
Part 3: Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (AESIs), and serious adverse events (SAEs)
时间窗: Through study termination, an average of 36 weeks
Part 3: Number of participants with clinically significant changes from baseline in Hematology parameters
时间窗: Through study termination, an average of 36 weeks
Part 3: Number of participants with clinically significant changes from baseline in Urinalysis parameters
时间窗: Through study termination, an average of 36 weeks
Part 3: Number of participants with clinically significant changes from baseline in Biochemistry parameters
时间窗: Through study termination, an average of 36 weeks
Part 3: Number of participants with clinically significant changes from baseline in vital signs
时间窗: Through study termination, an average of 36 weeks
Part 3: Number of participants with clinically significant changes from baseline in physical examinations
时间窗: Through study termination, an average of 36 weeks
Part 3: Number of participants with clinically significant changes in electrocardiogram (ECG)
时间窗: Through study termination, an average of 36 weeks
次要结局
- Part 1: Proportion of participants who are AAE-C1INH attack-free during Treatment Phase(12 weeks)
- Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during Treatment Phase(12 weeks)
- Part 1: Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during Treatment Phase(12 weeks)
- Part 1: Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during Treatment Phase(12 weeks)
- Part 1: Proportion of participants achieving ≥50%, ≥70% and ≥90% reduction in AAE-C1NH attack rate relative to baseline during Treatment Phase(12 weeks)
- Part 1: Incidence of TEAEs, treatment-emergent AESIs, and SAEs(12 weeks)
- Part 1: Number of participants with clinically significant changes from baseline in Hematology parameters(12 weeks)
- Part 1: Number of participants with clinically significant changes from baseline in Urinalysis parameters(12 weeks)
- Part 1: Number of participants with clinically significant changes from baseline in Biochemistry parameters(12 weeks)
- Part 1: Number of participants with clinically significant changes from baseline in Vital signs(12 weeks)
- Part 1: Number of participants with clinically significant changes from baseline in physical examination(12 weeks)
- Part 1: Number of participants with clinically significant changes from baseline in ECG parameters(12 weeks)
- Part 1: Pre-dose plasma concentrations of Deucrictibant(At Weeks 6 and 12)
- Part 1: Pre-dose plasma concentrations of deucrictibant metabolites(At Weeks 6 and 12)
- Part 1: Pharmacokinetics [PK]: Urine concentrations of Deucrictibant and deucrictibant metabolites(At Week 12)
- Part 1: Change from baseline in Angioedema Quality of Life (AE-QoL) questionnaire total score, functioning domain score, and fears/shame domain score(Baseline (Day 1) and at Weeks 4, 8 and 12)
- Part 1: Change from baseline in Angioedema Control Test 4-week version (AECT-4wk)(Baseline (Day 1) and at Week 12)
- Part 1: Patient Global Assessment-Status (PGA-S) at baseline(At Baseline (Day 1))
- Part 1: Patient Global Assessment of Change (PGA-Change) at Week 12(At Week 12)
- Part 1: Change from baseline in EuroQol 5 Dimension 5 level (EQ 5D 5L)(Baseline (Day 1) and at Week 12)
- Part 2: Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms(sustained within 24 hours post-treatment)
- Part 2: Time to symptom relief defined as PGI-S rating of at least 1 point reduction(12 hours post-treatment)
- Part 2: Proportion of study drug-treated attacks achieving complete symptom resolution defined as achieving PGI- S rating of "no symptoms"(At 24 hours post-treatment)
- Part 2: Time to onset of symptom relief, defined as PGI-C rating of at least "a little better"(Within 12 hours post-treatment)
- Part 2: Time to End of Progression (EoP) in attack symptoms(Within 12 hours post-treatment)
- Part 2: Incidence of TEAEs, treatment-emergent AESIs, and SAEs(Up to 24 weeks)
- Part 2: Number of participants with clinically significant changes from baseline in Hematology parameters(24 weeks)
- Part 2: Number of participants with clinically significant changes from baseline in Urinalysis parameters(24 weeks)
- Part 2: Number of participants with clinically significant changes from baseline in Biochemistry parameters(24 weeks)
- Part 2: Number of participants with clinically significant changes from baseline in Vital signs(24 weeks)
- Part 2: Number of participants with clinically significant changes from baseline in physical examination(24 weeks)
- Part 2: Number of participants with clinically significant changes from baseline in ECG parameters(24 weeks)
- Part 2: Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles(Day 1)
- Part 3: Time to symptom relief, as PGI-C rating of at least "better"(12 hours post-treatment)
- Part 3: Time to symptom relief, as PGI-S rating of at least 1 point reduction(12 hours post-treatment)
- Part 3: Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of "no symptoms"(24 hours post-treatment)