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Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD)

Primary Purpose

LCA5

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV8.hLCA5
Sponsored by
Opus Genetics, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for LCA5 focused on measuring LCA, Retinal Degeneration, IRD, adeno associated virus, gene therapy, LCA5

Eligibility Criteria

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

Inclusion Criteria: Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures. Are willing to adhere to the clinical protocol and able to perform testing procedures. Participants must be at least 18 years of age at consent. Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Visual acuity: BCVA < 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT) Participant is a good candidate for surgery per investigator judgement Participant agrees to follow direction of investigator regarding restrictions post-surgery. Exclusion Criteria: Individuals of childbearing potential (male and female) who are pregnant or unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration. Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised. History of intraocular surgery for either eye within 6 months prior to planned IP administration. Have previously received gene therapy. Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period. History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results. Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision. Any absolute contraindication to a course of oral steroids. Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.

Sites / Locations

  • University of Pennsylvania Perelman School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Group 1

Dose Group 2

Dose Group 3

Arm Description

Single, unilateral subretinal administration of a low dose of OPGx-001 to adult participants at least 18 years of age

Single, unilateral subretinal administration of an intermediate dose of OPGx-001 to adult participants at least 18 years of age

Single, unilateral subretinal administration of a high dose of OPGx-001 to adult participants at least 18 years of age

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities
Number of adverse events related to OPGx-001
Number of procedure-related adverse events
Change in retinal thickness (as measured by OCT)
Changes from baseline in total retinal thickness and outer retinal thickness (in microns)

Secondary Outcome Measures

Change from baseline to month 12 in retinal sensitivity as measured by full-field stimulus testing (FST)
Change from baseline to month 12 in best corrected visual acuity (BCVA)
Change from baseline to month 12 in oculomotor control and fixation stability
Change from baseline to month 12 in dark-adapted transient pupillary light reflexes (TPLR)
Change from baseline to month 12 in visual functioning questionnaire

Full Information

First Posted
November 7, 2022
Last Updated
June 15, 2023
Sponsor
Opus Genetics, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT05616793
Brief Title
Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD)
Official Title
An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2023 (Actual)
Primary Completion Date
August 30, 2024 (Anticipated)
Study Completion Date
September 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Opus Genetics, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this clinical trial is to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene.
Detailed Description
This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating two doses of OPGx-001 for the treatment of LCA5-IRD. Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
LCA5
Keywords
LCA, Retinal Degeneration, IRD, adeno associated virus, gene therapy, LCA5

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Group 1
Arm Type
Experimental
Arm Description
Single, unilateral subretinal administration of a low dose of OPGx-001 to adult participants at least 18 years of age
Arm Title
Dose Group 2
Arm Type
Experimental
Arm Description
Single, unilateral subretinal administration of an intermediate dose of OPGx-001 to adult participants at least 18 years of age
Arm Title
Dose Group 3
Arm Type
Experimental
Arm Description
Single, unilateral subretinal administration of a high dose of OPGx-001 to adult participants at least 18 years of age
Intervention Type
Biological
Intervention Name(s)
AAV8.hLCA5
Intervention Description
Adeno-associated virus vector expressing human LCA5 gene
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities
Time Frame
1 year
Title
Number of adverse events related to OPGx-001
Time Frame
1 year
Title
Number of procedure-related adverse events
Time Frame
1 year
Title
Change in retinal thickness (as measured by OCT)
Description
Changes from baseline in total retinal thickness and outer retinal thickness (in microns)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Change from baseline to month 12 in retinal sensitivity as measured by full-field stimulus testing (FST)
Time Frame
1 year
Title
Change from baseline to month 12 in best corrected visual acuity (BCVA)
Time Frame
1 year
Title
Change from baseline to month 12 in oculomotor control and fixation stability
Time Frame
1 year
Title
Change from baseline to month 12 in dark-adapted transient pupillary light reflexes (TPLR)
Time Frame
1 year
Title
Change from baseline to month 12 in visual functioning questionnaire
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures. Are willing to adhere to the clinical protocol and able to perform testing procedures. Participants must be at least 18 years of age at consent. Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Visual acuity: BCVA < 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT) Participant is a good candidate for surgery per investigator judgement Participant agrees to follow direction of investigator regarding restrictions post-surgery. Exclusion Criteria: Individuals of childbearing potential (male and female) who are pregnant or unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration. Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised. History of intraocular surgery for either eye within 6 months prior to planned IP administration. Have previously received gene therapy. Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period. History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results. Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision. Any absolute contraindication to a course of oral steroids. Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Tuller
Phone
8608882718
Email
STuller@OpusGtx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jasminder Soto
Facility Information:
Facility Name
University of Pennsylvania Perelman School of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariejel Weber
Phone
215-662-6396
Email
mariejel.weber@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Tomas Aleman, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD)

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