A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)

Phase 1

Recruiting

• Conditions: Muscular Dystrophy; Fukutin Related Protein; Limb-Girdle Muscular Dystrophy Type 2; LGMD2; LGMD; FKRP; FKRP Mutation; Limb Girdle Muscular Dystrophy; LGMD2I
• Interventions: Genetic: AB-1003 dose level 2; Genetic: AB-1003 dose level 1; Other: Placebo

• Registration Number: NCT05230459
• Lead Sponsor: Asklepios Biopharmaceutical, Inc.

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-27
• Study First Submitted QC: 2022-01-27
• Study First Posted: 2022-02-09
• Study Start: 2023-05-15
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-28
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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 ascend 4 stairs between 2.5 and 10 seconds.
3. Ability to walk/run 10 meters in <30 seconds.
4. Able to understand and comply with all study procedures.
5. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AB-1003 Cohort 2	AB-1003 dose level 2	-
AB-1003 Cohort 1	AB-1003 dose level 1	-
Placebo (Cohorts 1 and 2)	Placebo	-

Primary Outcome Measures

Name	Time	Method
Adverse Events	0-52 weeks	Treatment Emergent Adverse Events, Serious Adverse Events, Dose Limiting Toxicity

Trial Locations

Locations (6)

Kennedy Krieger Institute; 🇺🇸 Baltimore, Maryland, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

University of California - Irvine; 🇺🇸 Irvine, California, United States

VCU; 🇺🇸 Richmond, Virginia, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States