Long-Term, Open-label Study of Oral Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With HAE

Официальное название

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

Обзор

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

Подробное описание

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 130 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 daily, and also complete questionnaires at predefined timepoints during the study.

Вмешательства

• Препарат Deucrictibant
  Deucrictibant extended-release tablet for once daily oral use

Первичные конечные точки

• Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation [Срок оценки: 130 weeks]
• Change in heart rate [Срок оценки: 130 weeks]
• Change in blood pressure [Срок оценки: 130 weeks]
• Change in body temperature [Срок оценки: 130 weeks]
• Change in clinical laboratory tests from baseline [Срок оценки: 130 weeks]
• Change in electrocardiograms (ECGs) from baseline [Срок оценки: 130 weeks]

Вторичные конечные точки (12)

• Time-normalized number of Investigator-confirmed HAE attacks during the Treatment Period [Срок оценки: 130 weeks]
• Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the Treatment Period [Срок оценки: 130 weeks]
• Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during Treatment Period [Срок оценки: 130 weeks]
• Time-normalized number of Investigator-confirmed severe HAE attacks during the Treatment Period [Срок оценки: 130 weeks]
• Proportion of time without angioedema symptoms during the Treatment Period [Срок оценки: 130 weeks]
• Patient reported outcome: Angioedema Quality of Life (AE-QoL) questionnaire [Срок оценки: 130 weeks]
• Patient reported outcome: Patient Global Assessment of Change (PGA-Change) [Срок оценки: 130 weeks]
• Patient reported outcome: Angioedema Control Test 4-week version (AECT-4wk) [Срок оценки: 130 weeks]
• Patient reported outcome: Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP) [Срок оценки: 130 weeks]
• Patient reported outcome: Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) [Срок оценки: 130 weeks]
• Pharmacokinetics [PK]: Pre-dose plasma concentration of deucrictibant and deucrictibant metabolites (Ctrough) [Срок оценки: 130 weeks]
• Pharmacokinetics [PK]: Urine concentration of deucrictibant and deucrictibant metabolites [Срок оценки: 130 weeks]

Критерии участия

Критерии включения

• 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 eDiary and ePRO data recording.
• Female participants of childbearing must agree to the protocol specified pregnancy testing and contraception methods.

Критерии исключения

• 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 ACE inhibitors or any estrogen-containing medications with systemic absorption 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 randomization
• Known hypersensitivity to deucrictibant or any of the excipients of the study drug

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 12 центров

• Study Site — Birmingham
• Study Site — Scottsdale
• Study Site — Little Rock
• Study Site — San Diego
• Study Site — Santa Monica
• Study Site — Walnut Creek
• Study Site — Wheaton
• Study Site — St Louis
• … и ещё 4 центра

Великобритания · 10 центров

• Study Site — Birmingham
• Study Site — Birmingham
• Study Site — Brighton
• Study Site — Bristol
• Study Site — Cambridge
• Study Site — London
• Study Site — London
• Study Site — Oxford
• … и ещё 2 центра

Бразилия · 5 центров

• Study Site — Ribeirão Preto
• Study Site — Salvador
• Study Site — Santo André
• Study Site — São Paulo
• Study Site — São Paulo

Австралия · 4 центра

• Study Site — Melbourne
• Study Site — Melbourne
• Study Site — Perth
• Study Site — Sydney

Япония · 4 центра

• Study Site — Hiroshima
• Study Site — Kanagawa
• Study Site — Osaka
• Study Site — Tokyo

Аргентина · 3 центра

• Study Site — Corrientes
• Study Site — Pilar
• Study Site — Salta

Германия · 3 центра

• Study Site — Berlin
• Study Site — Frankfurt
• Study Site — Munich

Италия · 3 центра

• Study Site — Padova
• Study Site — Palermo
• Study Site — Roma

Turkey (Türkiye) · 3 центра

• Study Site — Ankara
• Study Site — Istanbul
• Study Site — Izmir

Канада · 2 центра

• Study Site — Edmonton
• Study Site — Montreal

South Korea · 2 центра

• Study Site — Daegu
• Study Site — Seoul

Австрия · 1 центр

• Study Site — Vienna

Болгария · 1 центр

• Study Site — Sofia

Китай · 1 центр

• Study Site — Пекин

Франция · 1 центр

• Study Site — Grenoble

Гонконг · 1 центр

• Study Site — Гонконг

Венгрия · 1 центр

• Study Site — Budapest

Ирландия · 1 центр

• Study Site — Dublin

Польша · 1 центр

• Study Site — Krakow

Словакия · 1 центр

• Study Site — Martin

ЮАР · 1 центр

• Study Site — Cape Town

Испания · 1 центр

• Study Site — Barcelona

Идентификаторы

NCT: NCT06679881 · PHA022121-C307

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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