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

Primary Purpose

Limb Girdle Muscular Dystrophy, Limb-Girdle Muscular Dystrophy Type 2, LGMD2I

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LION-101 dose level 1

LION-101 dose level 2

Placebo

About this trial

This is an interventional treatment trial for Limb Girdle Muscular Dystrophy focused on measuring gene therapy, LGMD2I, LGMD2I/R9, gene augmentation therapy, FKRP, fukutin related protein, FKRP mutation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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.
Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine.
Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images.
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).
Abnormal renal function (GFR < 60 ml/min, using the MDRD equation).
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).
In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits.
Requirement for daytime ventilatory support.
Change in glucocorticosteroid treatment within 3 months prior to baseline visit.
Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy.
Ongoing participation in any other therapeutic clinical trial.
Neutralizing antibody titer to AAV9 ≥ 1:5.
Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.

Sites / Locations

University of California - IrvineRecruiting
University of IowaRecruiting
VCURecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

LION-101 Cohort 1

LION-101 Cohort 2

Placebo (Cohorts 1 and 2)

Arm Description

Outcomes

Primary Outcome Measures

Adverse Events

Treatment Emergent Adverse Events, Serious Adverse Events, Dose Limiting Toxicity

Secondary Outcome Measures

Full Information

NCT ID

NCT05230459

First Posted

January 27, 2022

Last Updated

May 22, 2023

Sponsor

Asklepios Biopharmaceutical, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05230459

Brief Title

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

Official Title

A Phase 1/2, Double-blind, Randomized, Placebo-controlled, Dose-escalation Study to Evaluate the Safety of LION-101 Gene Therapy in Adult Subjects (18-65 Years) With Genetic Confirmation of Limb Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) - Part 1

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 12, 2023 (Actual)

Primary Completion Date

December 2028 (Anticipated)

Study Completion Date

December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Asklepios Biopharmaceutical, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

LION-101 Cohort 1

Arm Type

Experimental

Arm Title

LION-101 Cohort 2

Arm Type

Experimental

Arm Title

Placebo (Cohorts 1 and 2)

Arm Type

Placebo Comparator

Intervention Type

Genetic

Intervention Name(s)

LION-101 dose level 1

Intervention Description

Single intravenous infusion of LION-101 gene therapy at dose level 1

Intervention Type

Genetic

Intervention Name(s)

LION-101 dose level 2

Intervention Description

Single intravenous infusion of LION-101 gene therapy at dose level 2

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Single intravenous infusion of Placebo

Primary Outcome Measure Information:

Title

Adverse Events

Description

Treatment Emergent Adverse Events, Serious Adverse Events, Dose Limiting Toxicity

Time Frame

0-52 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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. Ability to ascend 4 stairs between 2.5 and 10 seconds. Ability to walk/run 10 meters in < 30 seconds. Able to understand and comply with all study procedures. 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: 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. Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine. Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images. 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). Abnormal renal function (GFR < 60 ml/min, using the MDRD equation). 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). In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits. Requirement for daytime ventilatory support. Change in glucocorticosteroid treatment within 3 months prior to baseline visit. Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy. Ongoing participation in any other therapeutic clinical trial. Neutralizing antibody titer to AAV9 ≥ 1:5. Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Medical Affairs at AskBio

Phone

(919) 561-6210

AskFirst@askbio.com

Facility Information:

Facility Name

University of California - Irvine

City

Irvine

State/Province

California

ZIP/Postal Code

92697

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

UCI Alpha Clinic

stemcell@uci.edu

First Name & Middle Initial & Last Name & Degree

Tahseen Mozaffar, MD

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ciara Gibbs

ciara-gibbs@uiowa.edu

First Name & Middle Initial & Last Name & Degree

Katherine Mathews, MD

Facility Name

VCU

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Abel Bulti

abel.bulti@vcuhealth.org

First Name & Middle Initial & Last Name & Degree

Nicholas E Johnson, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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