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)

Trial ID: NCT05230459

Interventional - Phase 1/2 - Active, not recruiting

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)

Conditions

• Limb Girdle Muscular Dystrophy
• Limb-Girdle Muscular Dystrophy Type 2
• LGMD2I
• Muscular Dystrophy
• LGMD2
• LGMD
• FKRP
• FKRP Mutation
• Fukutin Related Protein

Interventions

• AB-1003 dose level 1
• AB-1003 dose level 2
• Placebo

Eligibility

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.

Sponsor

AskBio Inc

Source: ClinicalTrials.gov

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