Evaluating the safety of AB-1003 for patients with LGMD2I/R9

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)

This study is testing the safety of a new treatment called AB-1003 in adults with limb girdle muscular dystrophy type 2I/R9 to see how well they can handle it.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: AskBio Inc (Industry-sponsored)
• Locations: 6 sites (Irvine, California and 5 other locations)
• Trial ID: NCT05230459 on ClinicalTrials.gov

What this trial studies

This study aims to assess 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 cohorts with varying doses of the drug, alongside a placebo group. The study focuses on individuals with a confirmed FKRP gene mutation and evaluates their ability to perform specific physical tasks. The goal is to gather data on the safety profile of the treatment in this patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 65 with a clinical diagnosis of LGMD2I/R9 and confirmed FKRP gene mutation.

Not a fit: Patients with significant cardiomyopathy or other serious heart conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from LGMD2I/R9, potentially improving their quality of life.

How similar studies have performed: Other studies involving gene therapy for muscular dystrophies have shown promise, indicating potential for success with this approach.

Eligibility criteria

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.

Where this trial is running

Irvine, California and 5 other locations

• University of California - Irvine — Irvine, California, United States (Recruiting)
• University of Iowa — Iowa City, Iowa, United States (Recruiting)
• University of Kansas Medical Center — Kansas City, Kansas, United States (Recruiting)
• Kennedy Krieger Institute — Baltimore, Maryland, United States (Recruiting)
• Vcu — Richmond, Virginia, United States (Recruiting)
• University of Washington Medical Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Study coordinator: AskFirst Patient Engagement

Conditions Limb Girdle Muscular Dystrophy; Limb-Girdle Muscular Dystrophy Type 2; LGMD2I; Muscular Dystrophy; LGMD2; LGMD; FKRP; FKRP Mutation