A Phase 2 Study of CRD-4730 in CPVT

Официальное название

A Phase 2, Double-Blind, Repeat-Dose, Placebo-Controlled Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CRD-4730 In Participants With Catecholaminergic Polymorphic Ventricular Tachycardia

Обзор

This is a Phase 2, multicenter, double-blind, sponsor blinded, placebo-controlled, repeat-dose clinical study of CRD-4730 to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CRD-4730 to participants with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Participants with CPVT will complete a 3-period, randomized 3-sequence study. Each participant will be randomized to one of the 3 sequences in which they will receive 2 different doses of CRD-4730 and 1 dose of matching placebo.

Вмешательства

• Препарат CRD-4730
  Oral CRD-4730 in tablet form
• Препарат Placebo
  Placebo to match CRD-4730 in tablet form

Первичные конечные точки

• Primary Outcome Measures [Срок оценки: Baseline to Day 101]

Вторичные конечные точки (2)

• Secondary Outcome Measure [Срок оценки: Baseline to Day 15; Baseline to Day 44; Baseline to Day 73]
• Secondary Outcome Measures [Срок оценки: Baseline to Day 15; Baseline to Day 44; Baseline to Day 73]

Критерии участия

Критерии включения

Each participant must meet all the following criteria to be enrolled in this study:

• The participant is male or female, ≥18 years of age and of legal adult age in accordance with local requirements.
• The participant has a confirmed CPVT diagnosis, based on genetic screening for a pathogenic ryanodine receptor (RYR2) mutation and a clinical phenotype consistent with CPVT at Screening. Previous CPVT genetic testing documented in medical history is acceptable if confirmed by the Investigator and documented in the study source records.
• The participant can perform an EST during which frequent premature ventricular contractions (PVCs; ≥10 per minute), ventricular bigeminy, or higher-grade VA (equivalent to a VA score ≥2) are identified by the Investigator.
• The participant has been on a stable dose of at least 1 antiarrhythmic medication (including beta blockers but not amiodarone) for 4 weeks prior to Screening, unless the participant has been unable to tolerate antiarrhythmic therapy previously.
• Adheres to all contraceptive criteria.

Критерии исключения

Participants meeting any of the following criteria will be excluded from the study:

• The participant has clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease.
• The participant has a clinically significant abnormal ECG not explained by the diagnosis of CPVT at Screening or clinically significant abnormal intervals, such as prolonged QT.
• The participant has a history of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of Screening.
• The participant undergoes implantable cardioverter-defibrillator (ICD) implantation or has sympathetic nerve denervation within 3 months of Screening.
• The participant has an anticipated change in exercise regimen or new exercise program during the course of the study.
• The participant has a history of malignancy within the past 5 years at Screening, with the exception of successfully treated basal cell carcinoma or nonmetastatic squamous cell carcinoma of the skin or cervical carcinoma in situ. Prior exposure to chest radiation for any malignancy is exclusionary.
• The participant has abnormal blood pressure, defined as supine symptomatic hypotension, systolic blood pressure >150 mm Hg or diastolic blood pressure >90 mm Hg, or symptomatic bradycardia or a heart rate >100 bpm at Screening and/or on Day 1. Blood pressure and pulse should be measured after the participant has been in the seated position after 5 minutes of rest.
• The participant has hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × (upper limit of normal \[ULN\]) and/or total bilirubin >1.5 × ULN at Screening (unless secondary to confirmed Gilbert syndrome).
• The participant has acute or chronic hepatitis B (HBV; defined as hepatitis B surface antigen \[HBsAg\] reactive), acute or chronic hepatitis C virus (HCV; defined as detection of HCV antibody and RNA \[qualitative\]), or human immunodeficiency virus (HIV) infection.
• The female participant is pregnant, lactating/breastfeeding, or has plans to become pregnant during the study or within 3 months following the last study drug administration.
• The participant has taken any antiarrhythmic drug in addition to their stable, chronic regimen unless it has been at least 5 half-lives since administration at the time of Screening.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Cardurion Investigative Site — San Francisco
• Cardurion Investigative Site — Morrisville
• Cardurion Investigative Site — Houston
• Cardurion Investigative Site — Salt Lake City
• Cardurion Investigative Site — Madison

Франция · 3 центра

• Cardurion Investigative Site — Bron
• Cardurion Investigative Site — Paris
• Cardurion Investigative Site — Saint-Herblain

Канада · 1 центр

• Cardurion Investigative Site — Vancouver

Италия · 1 центр

• Cardurion Investigative Site — Pavia

Нидерланды · 1 центр

• Cardurion Investigative Site — Amsterdam

Испания · 1 центр

• Cardurion Investigative Site — Esplugues de Llobregat

Публикации

• Takagahara, Shuichi, et al. "Novel, Potent, and Highly Selective Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Inhibitors Reduce Substrate Phosphorylation in Rat Hearts and Prolong Survival in a Mouse Model of Severe Heart Failure." Circulation 148.Suppl_1 (2023): A12726-A12726.

Идентификаторы

NCT: NCT06658899 · CRD-4730-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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