A Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias

Официальное название

A Phase 1 Open-label, Multicenter, First-in-human, Ascending Dose Trial Evaluating the Safety and Tolerability of a Lipid Nanoparticle Formulation of CRISPR-Guide RNA-Cas9 Nuclease (CTX310) for In Vivo Editing of the Angiopoietin-like 3 (ANGPTL3) Gene in Participants With Refractory Dyslipidemias

Обзор

This is a single-arm, open-label, multicenter, ascending dose Phase 1 trial that will enroll participants 18 to 75 years of age with dyslipidemias that are refractory to available treatments.

Подробное описание

This is a phase 1, open-label, multi-center study of CTX310 in participants with refractory dyslipidemias. Subjects will receive a dose of CTX310 via intravenous (IV) infusion.

Вмешательства

• Препарат CTX310
  CTX310 is a lipid nanoparticle (LNP) formulation of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) components for in vivo editing of the target gene angiopoietin-like 3 (ANGPTL3).

Первичные конечные точки

• To evaluate the safety of CTX310 in adult subjects with dyslipidemias that are refractory to available treatments [Срок оценки: From CTX310 infusion up to 12 months]

Вторичные конечные точки (4)

• To assess the preliminary efficacy of CTX310 in adult participants with dyslipidemias that are refractory to available treatments [Срок оценки: Over 12 months, compared to baseline]
• To further characterize the safety of CTX310 in adult participants with dyslipidemias that are refractory to available treatments [Срок оценки: From CTX310 infusion up to 12 months]
• To assess the pharmacokinetics (PK) of CTX310 in adult participants with dyslipidemias that are refractory to available treatments [Срок оценки: From CTX310 infusion up to 12 months]
• To assess the pharmacodynamic (PD) response of CTX310 in adult participants with dyslipidemias that are refractory to available treatments [Срок оценки: Over 12 months, compared to baseline]

Критерии участия

Критерии включения

• Age of ≥18 and ≤75 years at the time of signing the informed consent.
• Able to provide written informed consent.
• Participants diagnosed with persistent dyslipidemias defined by TG ≥150 mg/dL - and LDL-C ≥70 mg/dL in participants with ASCVD, or LDL-C ≥70 or 100mg/dL in participants with or without ASCVD respectively, or TG ≥500 mg/dL.
• Refractory to the maximal intensity or MTD of standard of care lines of lipid-lowering therapies available through routine clinical care, for at least 12 weeks prior to screening
• Female participants must be postmenopausal or surgically sterile.
• All male participants and their female partners must agree to the use of an acceptable method of effective contraception for the duration of the study.

Критерии исключения

• Participants with familial chylomicronemia syndrome (FCS). Some exceptions may apply.
• Evidence of liver disease, defined as but not limited to:

LFTS >2 × upper limit of normal (ULN), or total bilirubin >2 × ULN, or INR >1.5 × ULN, or liver stiffness measured by liver elastography

• Abnormal or compromised function of kidney, heart, blood or liver.
• Acute coronary syndrome event or stroke within 24 weeks prior to Day 1. Acute pancreatitis within 12 weeks prior to Day 1.
• Current use or use within 365 days from Day 1 of any hepatocyte-targeted small interfering RNA (except inclisiran).
• Positive serology for HIV, hepatitis B or hepatitis C (antibody, surface antigen orNAT). Serology consistent with prior immunization will be eligible for the trial.
• Any prior malignancy within the past 5 years, or current malignancy (exceptions for resected or removed basal cell carcinoma, squamous cell carcinoma in situ and carcinoma in situ of the cervix or breast).
• Women of childbearing potential.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Note: The inclusion and exclusion criteria listed represent the global protocol. Additional or modified eligibility criteria may apply in certain countries in accordance with local regulatory and ethics committee requirements and the approved country-specific protocol.

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 · 9 центров

• Integrity Clinical Research — Hialeah
• Jacksonville Center for Clinical Research — Jacksonville
• Flourish Orlando — Orlando
• United Medical Research — Port Orange
• University of Rochester — Rochester
• Duke Early Phase Clinical Research — Durham
• Peters Medical Research — High Point
• Cleveland Clinic — Cleveland
• … и ещё 1 центр

Австралия · 5 центров

• Royal Adelaide — Adelaide
• CORE Research — Brisbane
• Royal Prince Alfred Hospital — Camperdown
• Austin Health — Heidelberg
• Monash Medical Center — Melbourne

Великобритания · 3 центра

• Royal Papworth Hospital — Cambridge
• Barts — London
• Richmond Pharmacology — London

Новая Зеландия · 2 центра

• Aotearoa — Auckland
• NZCR — Christchurch

Идентификаторы

NCT: NCT07491172 · CRSP-CVD-400

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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