A Study to Evaluate the Safety of LION-101 in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of a single intravenous infusion of LION-101 in adults diagnosed with limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). Participants will be treated in sequential, dose-level cohorts. (Part 1)
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: LION-101 Cohort 1
|
Genetic: LION-101 dose level 1
Single intravenous infusion of LION-101 gene therapy at dose level 1
|
Experimental: LION-101 Cohort 2
|
Genetic: LION-101 dose level 2
Single intravenous infusion of LION-101 gene therapy at dose level 2
|
Placebo Comparator: Placebo (Cohorts 1 and 2)
|
Other: Placebo
Single intravenous infusion of Placebo
|
Outcome Measures
Primary Outcome Measures
- Adverse Events [0-52 weeks]
Treatment Emergent Adverse Events, Serious Adverse Events, Dose Limiting Toxicity
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female subjects between the ages 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation.
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Ability to ascend 4 stairs between 2.5 and 10 seconds.
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Ability to walk/run 10 meters in < 30 seconds.
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Able to understand and comply with all study procedures.
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Sexually active females of childbearing potential and female and male partners of male subjects receiving LION-101 must use a barrier method of contraception for the first 6 months after dosing.
Exclusion Criteria:
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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.
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Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine.
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Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images.
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History of chronic liver disease (e.g. hepatitis, HIV, steatosis) or abnormal liver function (abnormal GGT and/or abnormal total/direct bilirubin and/or AST and ALT >2 ULN).
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Abnormal renal function (GFR < 60 ml/min, using the MDRD equation).
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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).
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In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits.
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Requirement for daytime ventilatory support.
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Change in glucocorticosteroid treatment within 3 months prior to baseline visit.
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Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy.
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Ongoing participation in any other therapeutic clinical trial.
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Neutralizing antibody titer to AAV9 ≥ 1:5.
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Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Asklepios Biopharmaceutical, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LION-CS101