A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)

Официальное название

A Two-part Multicenter Study: a Randomized, Double-blind, Placebo-controlled Dose-escalation Safety Phase (Part 1) Followed by Double-blind, Placebo-controlled, Adaptive Phase (Part 2) Study to Evaluate the Safety and Efficacy of AB-1003 in Adult Subjects With LGMD2I/R9 Mutations in the Gene Encoding Fukutin Related Protein (FKRP)

Обзор

The purpose of this study is to evaluate the safety and tolerability of a single intravenous infusion of AB-1003 in adults diagnosed with limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). Participants will be treated in sequential, dose-level cohorts. (Part 1)

Вмешательства

• Генная терапия AB-1003 dose level 1
  Single intravenous infusion of AB-1003 gene therapy at dose level 1
• Генная терапия AB-1003 dose level 2
  Single intravenous infusion of AB-1003 gene therapy at dose level 2
• Другое Placebo
  Single intravenous infusion of Placebo

Первичные конечные точки

• Adverse Events [Срок оценки: 0-52 weeks]

Критерии участия

Критерии включения

• Male and female subjects aged 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation.
• Ability to walk/run 10 meters in <30 seconds.
• Able to understand and comply with all study procedures.
• Sexually active females of childbearing potential and female and male partners of male subjects receiving study intervention must use a barrier method of contraception for the first 6 months after dosing.

Критерии исключения

• Significant cardiomyopathy as defined by echocardiogram (left ventricular ejection fraction <40%), evidence of conduction defect (increased PR and RR intervals, left bundle branch block and QTcF >480m/sec), NYHA Class 3 or 4 heart failure, or MRI gadolinium enhancement evidence of clinically important myocardial fibrosis.
• Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine.
• Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images.
• History of active, ongoing chronic liver disease (e.g. hepatitis, HIV-related liver disease, hemochromatosis, steatosis, etc.) or abnormal liver function tests (abnormal GGT and/or abnormal total/direct bilirubin >upper limit of normal \[ULN\] and/or elevated AST and ALT >2 ULN).
• Abnormal renal function (GFR <60 ml/min, using the Modification of Diet in Renal Disease equation).
• Any life-threatening disease, including malignant neoplasms and medical history or malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer).
• In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits.
• Requirement for daytime ventilatory support.
• Change in glucocorticosteroid treatment within 3 months prior to screening visit.
• Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy.
• Ongoing participation in any other therapeutic clinical trial.
• Neutralizing antibody titer to AAV9 >1:5.
• Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 6 центров

• University of California - Irvine — Irvine
• University of Iowa — Iowa City
• University of Kansas Medical Center — Kansas City
• Kennedy Krieger Institute — Baltimore
• VCU — Richmond
• University of Washington Medical Center — Seattle

Идентификаторы

NCT: NCT05230459 · LION-CS101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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