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

Neovascular Age-related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04832724
• Other study ID #: RGX-314-2103
• Status: Completed
• Phase: Phase 2
• Start date: February 22, 2021
• Est. completion date: March 18, 2024

Study information

• Verified date: April 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 18, 2024
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 89 Years

Eligibility

Inclusion Criteria:

1. Males or females, aged = 50 years and = 89 years.

2. An Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA-letter score between = 78 and = 40 in the study eye at Screening.

3. Diagnosis of choroidal neovascularization (CNV) secondary to age-related macular degeneration in the study eye previously treated with anti-VEGF.

4. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry.

5. Willing and able to provide written, signed informed consent for this study.

6. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye.

Exclusion Criteria:

1. CNV or macular edema in the study eye secondary to any causes other than AMD.

2. Subfoveal fibrosis or atrophy in study eye.

3. Any condition in the investigator's opinion that could limit visual acuity improvement in the study eye.

4. Active or history of retinal detachment or retinal tear in the study eye.

5. Advanced glaucoma in the study eye.

6. Prior treatment with gene therapy.

7. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Genetic:
• RGX-314
RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein

Locations

Country	Name	City	State
United States	Eye Associates of New Mexico	Albuquerque	New Mexico
United States	Wilmer Eye Institute	Baltimore	Maryland
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Texas Retina Associates	Dallas	Texas
United States	Charles Retina Institute	Germantown	Tennessee
United States	Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Retinal Consultants of Arizona	Phoenix	Arizona
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Vitreous Associates of Florida	Saint Petersburg	Florida
United States	Retina Consultants of San Diego	San Diego	California
United States	California Retina Consultants	Santa Barbara	California
United States	Barnet Dulaney Perkins Eye Center	Sun City	Arizona
United States	Retina Consultants of Texas	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

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