RGX-314 Gene Therapy Pharmacodynamic Study for Neovascular Age-related Macular Degeneration (nAMD)

Sponsor

REGENXBIO, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04832724

Collaborator

(none)

Enrollment

Locations

Arms

17.2

Anticipated Duration (Months)

4.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (nAMD) also referred to as Wet AMD. Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. The purpose of this phase 2, open label study is to evaluate whether different doses of RGX-314 from two different formulations (clinical versus eventual commercial formulation) perform the same in humans when delivered by subretinal administration

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration Wet Macular Degeneration Wet Age-related Macular Degeneration	Genetic: RGX-314	Phase 2

Detailed Description

Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long repeated intraocular injections to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. RGX-314 is being developed as a potential one-time treatment for wet AMD. RGX-314 uses an AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds to and neutralizes VEGF activity. This phase 2, open label study will explore the pharmacodynamics of two doses in two formulations of RGX-314 gene therapy via subretinal delivery in patients with neovascular Age-related Macular Degeneration. Approximately 60 patients (15 per cohort) who meet the inclusion/exclusion criteria will be enrolled in 4 sequential dose cohorts. A dose cohort will be comprised of 1 of 2 doses of RGX-314 in 1 of 2 formulations in order to explore the pharmacodynamics of RGX-314 based on aqueous humor transgene product (TP) concentrations. If the participants meet the study criteria and choose to participate in the study, their participation in the study will last about 12 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-label Study to Explore the Pharmacodynamics of Two Doses in Two Formulations of RGX-314 Gene Therapy Administered Via Subretinal Delivery in Participants With Neovascular Age-related Macular Degeneration

Actual Study Start Date :

Feb 22, 2021

Anticipated Primary Completion Date :

Jul 30, 2022

Anticipated Study Completion Date :

Jul 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Commercial Formulation Dose 1 Dose 1 of RGX-314	Genetic: RGX-314 RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Clinical Formulation Dose 1 Dose 1 of RGX-314	Genetic: RGX-314 RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Commercial Formulation Dose 2 Dose 2 of RGX-314	Genetic: RGX-314 RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Clinical Formulation Dose 2 Dose 2 of RGX-314	Genetic: RGX-314 RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein

Outcome Measures

Primary Outcome Measures

RGX-314 target protein concentration in aqueous humor [At Week 24]

Secondary Outcome Measures

Incidence and severity of ocular Adverse Events (AEs) and overall AEs [Through Week 48]
Evaluate the safety and tolerability of RGX-314
Changes in Best Corrected Visual Acuity (BCVA) [At Week 24 and 48]
BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Changes in Central Retinal Thickness (CRT) [At Week 24 and 48]
CRT is measured by spectral domain optical coherence tomography (SD-OCT)
Mean Supplemental anti-VEGF injection annualized rate through week 24 and week 48 [Through Week 24 and week 48]
To assess the need for supplemental anti-VEGF therapy over 48 weeks

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females, aged ≥ 50 years and ≤ 89 years.
An Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA-letter score between ≤ 78 and ≥ 40 in the study eye at Screening.
Diagnosis of choroidal neovascularization (CNV) secondary to age-related macular degeneration in the study eye previously treated with anti-VEGF.
Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry.
Willing and able to provide written, signed informed consent for this study.
Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye.

Exclusion Criteria:

CNV or macular edema in the study eye secondary to any causes other than AMD.
Subfoveal fibrosis or atrophy in study eye.
Any condition in the investigator's opinion that could limit visual acuity improvement in the study eye.
Active or history of retinal detachment or retinal tear in the study eye.
Advanced glaucoma in the study eye.
Prior treatment with gene therapy.
Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix location	Phoenix	Arizona	United States	85014
2	San Diego location	San Diego	California	United States	92064
3	Santa Barbara location	Santa Barbara	California	United States	93103
4	Santa Maria location	Santa Maria	California	United States	93309
5	Saint Petersburg Location	Saint Petersburg	Florida	United States	33711
6	Baltimore location	Baltimore	Maryland	United States	21287
7	Boston location	Boston	Massachusetts	United States	02114
8	Reno location	Reno	Nevada	United States	89502
9	Albuquerque location	Albuquerque	New Mexico	United States	87109
10	Philadelphia location	Philadelphia	Pennsylvania	United States	19107
11	Memphis location	Germantown	Tennessee	United States	38138
12	Dallas Location	Dallas	Texas	United States	75231
13	Woodlands location	The Woodlands	Texas	United States	77384