FKRP, FKRP Mutation, Fukutin Related Protein, LGMD, LGMD2, LGMD2I, Limb Girdle Muscular Dystrophy, Limb-Girdle Muscular Dystrophy Type 2, Muscular Dystrophy
Conditions
Keywords
gene therapy, LGMD2I, LGMD2I/R9, gene augmentation therapy, FKRP, fukutin related protein, FKRP mutation
Brief summary
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
GENETICAB-1003 dose level 1
Single intravenous infusion of AB-1003 gene therapy at dose level 1
GENETICAB-1003 dose level 2
Single intravenous infusion of AB-1003 gene therapy at dose level 2
DRUGPlacebo
Single intravenous infusion of Placebo
Sponsors
AskBio Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects aged 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation. 2. Ability to walk/run 10 meters in \<30 seconds. 3. Able to understand and comply with all study procedures. 4. 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
1. 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. 2. Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine. 3. Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images. 4. 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). 5. Abnormal renal function (GFR \<60 ml/min, using the Modification of Diet in Renal Disease equation). 6. 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). 7. In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits. 8. Requirement for daytime ventilatory support. 9. Change in glucocorticosteroid treatment within 3 months prior to screening visit. 10. Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy. 11. Ongoing participation in any other therapeutic clinical trial. 12. Neutralizing antibody titer to AAV9 \>1:5. 13. Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 0-52 weeks | Treatment Emergent Adverse Events, Serious Adverse Events, Dose Limiting Toxicity |
Countries
United States
Outcome results
None listed