A Study to Evaluate the Pharmacodynamics and Safety of ARCT-810 in Participants With OTCD

Официальное название

A Phase 2a, Open-label, Multiple Ascending Dose Study to Evaluate the Pharmacodynamics and Safety of ARCT-810 in Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency

Обзор

Evaluate the safety and pharmacodynamics of multiple doses of ARCT-810 in adolescent and adult participants with OTC deficiency.

Подробное описание

This a Phase 2a, open-label study of ARCT-810 in participants 12 years of age and older living with OTC deficiency. After a diet stabilization period of at least 4 weeks, all participants will be enrolled to receive ARCT-810 every two weeks, for up to five doses, at one of three dose levels. Clinic visits will occur during screening and at Days 1, 15, 29, 36, 43, 57, 60, 71, and 85. During the study, participants will remain on their current clinical management for OTC deficiency. Dose escalation or cohort expansion may occur following completion of three participants at each dose level.

Вмешательства

• Биопрепарат ARCT-810
  ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) messenger RNA (mRNA) formulated in a lipid nanoparticle (LNP).

Первичные конечные точки

• Incidence, severity and dose-relationship of adverse events (AEs) [Срок оценки: Day 85]

Вторичные конечные точки (5)

• Stable isotope ureagenesis assay values (AUC of first isotope) [Срок оценки: Up to Day 85]
• Stable isotope ureagenesis assay values (AUC of second isotope) [Срок оценки: Up to Day 85]
• Fasting plasma ammonia [Срок оценки: Up to Day 85]
• Plasma Glutamine [Срок оценки: Up to Day 85]
• Plasma pharmacokinetics [Срок оценки: Up to Day 57]

Критерии участия

Критерии включения

• Willingness and ability to comply with all the protocol requirements, complete all study visits and sign informed consent.
• Males and Females aged ≥12 years, at Screening.
• Documented clinical diagnosis of OTC deficiency.
• History of symptomatic hyperammonemia or elevated plasma ammonia or glutamine with clinical stability for at least 1 month prior to Screening.
• Medically managed for OTC deficiency and receiving a stable protein-restricted diet, dietary supplements, and/or ammonia scavenger regimen (if applicable) for at least 28 days.
• Good general health with no clinically significant abnormal findings that would interfere with study procedures (including plasma ammonia within participant's historical range).
• Must be willing to adhere to contraception guidelines.

Критерии исключения

• Uncontrolled hypertension.
• Symptoms of infection for at least 7 days prior to dosing.
• Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
• History of any OTC gene therapy, or history of liver-derived stem cell therapy in the past 2 years.
• History of any organ transplant.
• History of severe allergic reaction to a liposomal or PEG-containing product.
• History of congenital or acquired cardiac disorders.
• Abuse of medications, illicit drugs or alcohol.
• Blood donation of 50 to 499 mL within 30 days of screening or of >499 mL within 60 days of screening.
• Clinically significant laboratory abnormalities on screening labs including INR >1.5, eGFR< 60 mL/min/1.73m2 or positive test results for HIV, HBV, or HCV.
• Inadequately controlled diabetes.
• Clinically significant anemia.
• Changes in maintenance therapies for OTC deficiency with 28 days prior to dosing.
• Medical history requiring continuous or intermittent systemic corticosteroid administration.
• Receipt of inhibitors of urea synthesis or drugs that significantly affect renal clearance.
• Recent treatment with another investigational drug, biological agent, or device.
• Treatment with any oligonucleotide (siRNA or mRNA) within 6 months prior to screening. COVID-19 vaccines are not exclusionary.
• Involved in study conduct or an immediate family member of an individual involved in the study.
• Participated in another dosing cohort of the study.
• Any other conditions, in the opinion of the investigator, that would interfere with participation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Uncommon Cures — Chevy Chase

Идентификаторы

NCT: NCT06488313 · ARCT-810-04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗