Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)

Официальное название

A Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept Study of ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)

Обзор

This is a 2-part study evaluating ATV-1601 in participants with moderate to severe HHT. Part 1 is a randomized, double-blind, placebo-controlled study evaluating 3 dosing regimens of ATV-1601. Patients completing Part 1 may participate in the Part 2 open-label extension to receive ATV-1601.

Подробное описание

Part 1: This is a Phase 1/2 proof-of-concept, double-blind, multicenter, placebo-controlled study to evaluate the safety, pharmacokinetics and efficacy of 3 oral dosing regimens of ATV-1601. Participants who meet eligibility requirements will be randomized in a double-blind manner to one of 3 doses of ATV-1601 or placebo. Participants will receive double-blind study treatment for a 16-week period.

Part 2: Eligible participants who complete Part 1 may enroll in an open-label extension study to receive up to 2 years of additional treatment. All participants in the open-label extension will receive ATV-1601. Once the recommended Phase 2 dose (RP2D) is determined based on Part 1, all participants in Part 2 will have the option to switch to the RP2D.

Вмешательства

• Препарат ATV-1601
  Administered orally, daily
• Препарат Placebo
  Administered orally, daily

Первичные конечные точки

• Part 1: Safety and tolerability [Срок оценки: 16 weeks]
• Part 2: Safety and tolerability [Срок оценки: 24 months]

Вторичные конечные точки (12)

• Part 1: Change in Epistaxis duration [Срок оценки: 16 weeks]
• Part 1: Epistaxis frequency [Срок оценки: 16 weeks]
• Part 1: Epistaxis intensity [Срок оценки: 16 weeks]
• Part 1: Intensity-weighted epistaxis duration [Срок оценки: 16 weeks]
• Part 1: Epistaxis Severity Score (ESS) [Срок оценки: 16 weeks]
• Part 1: Change in Hemoglobin [Срок оценки: 16 weeks]
• Part 1: Change in Parenteral iron use [Срок оценки: 16 weeks]
• Part 1: Change in Blood transfusion requirements [Срок оценки: 16 Weeks]
• Part 1: Pharmacokinetics - Maximum observed concentration (Cmax) [Срок оценки: 16 Weeks]
• Part 1: Pharmacokinetics - Area under the concentration-time curve over the dosing interval (AUCtau) [Срок оценки: 16 Weeks]
• Part 1: Pharmacokinetics - Area under the concentration-time curve extrapolated to infinity (AUCinf) [Срок оценки: 16 Weeks]
• Part 1: Pharmacokinetics - Time to maximum concentration (Tmax) [Срок оценки: 16 Weeks]

Критерии участия

Критерии включения

• Ability to provide informed consent prior to any study-specific procedures
• Confirmed diagnosis of hereditary hemorrhagic telangiectasia (HHT) based on Curaçao criteria
• Moderate to severe HHT with an ESS ≥ 4
• Anemia at Screening and/or requirement for at least 1 red-cell unit (RUE) in the previous 6 months
• Adequate hematologic, renal, and hepatic function per protocol-defined laboratory criteria
• Use highly effective contraception during the study and for a protocol-defined period after last dose

Критерии исключения

• Clinically significant abnormalities of glucose metabolism including diagnosed Type 1 or uncontrolled Type 2 diabetes
• Chronic cardiac disease, or cardiac rhythm abnormalities
• History of significant cardiovascular, hepatic, renal, or hematologic disease not related to HHT that may confound study results
• Use of prohibited concomitant medications within a protocol-defined washout period prior to first dose (including strong CYP modulators and certain herbal supplements)
• Recent (within 6 weeks) major surgery or local ablative procedures, or procedures on nasal telangiectasias
• Prior AKT inhibitor
• Pregnant or breastfeeding women

Additional Criteria for Open-Label Extension:

• Participants must complete the double-blind treatment period (Part 1)

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Massachusetts General Hospital — Boston

Идентификаторы

NCT: NCT07601425 · ATV-1601-102 · Harmony-HHT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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