Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant IR Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Deucrictibant
  Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use
• Препарат Placebo
  Part 1: Placebo Comparator tablet for once daily oral use
• Препарат Deucrictibant
  Part 2: Deucrictibant 20 mg soft capsule oral use
• Препарат Placebo
  Part 2: Placebo Comparator soft capsule oral use
• Препарат Deucrictibant
  Part 3: Deucrictibant 20 mg soft capsule oral use

Первичные конечные точки

• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: 12 weeks]
• Part 2 (On-demand, Double-blind Treatment Phase) [Срок оценки: 12 hours post-treatment]
• Part 3 (On-demand, Open-label Extension Treatment Phase) [Срок оценки: Through study completion, an average of 36 weeks]

Вторичные конечные точки (12)

• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: From enrollment through end of Part 1 (Week 12)]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: From enrollment through end of Part 1 (Week 12)]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: From enrollment through end of Part 1 (Week 12)]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Срок оценки: From enrollment through end of Part 1 (Week 12)]
• Part 2 (On-demand, Double-blind Treatment Phase) [Срок оценки: sustained within 24 hours post-treatment]
• Part 2 (On-demand, Double-blind Treatment Phase) [Срок оценки: 12 hours post-treatment]
• Part 2 (On-demand, Double-blind Treatment Phase) [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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
• Known hypersensitivity to deucrictibant or any of the excipients of the study drug
• Use of angiotensin-converting enzyme inhibitors or any estrogen-containing medications

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Великобритания · 6 центров

• Study Site — Bristol
• Study Site — Cambridge
• Study Site — Leicester
• Study Site — London
• Study Site — Newcastle upon Tyne
• Study Site — Plymouth

Италия · 5 центров

• Study Site 1 — Milan
• Study Site 2 — Milan
• Study Site 3 — Milan
• Study Site — Padova
• Study Site — Roma

США · 4 центра

• Study Site — San Diego
• Study Site — Walnut Creek
• Study Site — St Louis
• Study Site — Hershey

Франция · 3 центра

• Study Site — Grenoble
• Study Site — Lille
• Study Site — Paris

Германия · 3 центра

• Study Site — Berlin
• Study Site — Frankfurt am Main
• Study Site — Munich

Австралия · 1 центр

• Study Site — Clayton

Австрия · 1 центр

• Study Site — Vienna

Болгария · 1 центр

• Study Site — Sofia

Канада · 1 центр

• Study Site — Edmonton

Венгрия · 1 центр

• Study Site — Budapest

Нидерланды · 1 центр

• Study Site — Amsterdam

Новая Зеландия · 1 центр

• Study Site — Auckland

Польша · 1 центр

• Study Site — Krakow

Испания · 1 центр

• Study Site — Madrid

Швейцария · 1 центр

• Study Site — Basel

Turkey (Türkiye) · 1 центр

• Study Site — Ankara

Идентификаторы

NCT: NCT07266805 · PHA022121-C308

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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