Safety and efficacy of AB-1003 in subjects (ages 18-65) with LGMD2I/R9 impacting FKRP

UCI Specialty Area: Genetics

Principal Investigator: Tahseen Mozaffar

Official Title: 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)

A Study On:

Limb Girdle Muscular Dystrophy

Study Description

LGMD2I/R9 is a rare muscular dystrophy caused by mutations in the FKRP gene that codes for the fukutin-related protein (FKRP), partially responsible for the glycosylation of α dystroglycan (α-DG). Fully glycosylated α-DG is crucial to anchor the actin cytoskeleton of muscle fibers to the extracellular matrix. LION-101 is designed to express the FKRP protein primarily in muscle.

Eligibility

Male and female subjects aged 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation.
Ability to ascend 4 stairs between 2.5 and 10 seconds.
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 AB-1003 must use a barrier method of contraception for the first 6 months after dosing.

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 chronic liver disease (e.g. hepatitis, HIV, steatosis) or abnormal liver function (abnormal GGT and/or abnormal total/direct bilirubin and/or AST and ALT >2 ULN).
Abnormal renal function (GFR < 60 ml/min, using the MDRD 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 baseline 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.

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University of California, Irvine - Study Information Sheet

UCI Center for Clinical Research Potential Participant Database

Lead Researcher
Maheswari Senthil, MD
UCI Center for Clinical Research

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