A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: AB-1003 dose level 1, AB-1003 dose level 2, Placebo.
- Who it may be relevant to
- Registry conditions: Limb Girdle Muscular Dystrophy, Limb-Girdle Muscular Dystrophy Type 2, LGMD2I, Muscular Dystrophy. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
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)
Overview
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)
Interventions
- Genetic AB-1003 dose level 1
Single intravenous infusion of AB-1003 gene therapy at dose level 1 - Genetic AB-1003 dose level 2
Single intravenous infusion of AB-1003 gene therapy at dose level 2 - Other Placebo
Single intravenous infusion of Placebo
Primary outcome measures
- Adverse Events [Time frame: 0-52 weeks]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Sequential
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 6 centers
- 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
Identifiers
NCT: NCT05230459 · LION-CS101