Clinical trial NCT05230459: A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Limb Girdle Muscular Dystrophy
Limb-Girdle Muscular Dystrophy Type 2
LGMD2I
Muscular Dystrophy
LGMD2
LGMD
FKRP
FKRP Mutation
Fukutin Related Protein
Keywords: gene therapy
LGMD2I
LGMD2I/R9
gene augmentation therapy
FKRP
fukutin related protein
FKRP mutation
Lead sponsor: AskBio Inc
Sponsor class: INDUSTRY
First posted: 2022-02-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


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 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.

Primary outcomes:
measure: Adverse Events
timeFrame: 0-52 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California - Irvine
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Richmond
country: United States
facility: VCU
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
References: