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

• ClinicalTrials.gov Identifier: NCT04832724
• Recruitment Status: Completed
• First Posted: April 6, 2021
• Last Update Posted: April 12, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

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 (Clinical Trial)
• Actual 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: February 22, 2021
• Actual Primary Completion Date: October 2, 2023
• Actual Study Completion Date: March 18, 2024

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 :

1. RGX-314 target protein concentration in aqueous humor [ Time Frame: At Week 24 ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Retinal Consultants of Arizona

Phoenix, Arizona, United States, 85014

Barnet Dulaney Perkins Eye Center

Sun City, Arizona, United States, 85351

United States, California

Retina Consultants of San Diego

San Diego, California, United States, 92064

California Retina Consultants

Santa Barbara, California, United States, 93103

United States, Florida

Retina Vitreous Associates of Florida

Saint Petersburg, Florida, United States, 33711

United States, Maryland

Wilmer Eye Institute

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States, 02114

United States, Nevada

Sierra Eye Associates

Reno, Nevada, United States, 89502

United States, New Mexico

Eye Associates of New Mexico

Albuquerque, New Mexico, United States, 87109

United States, Pennsylvania

Wills Eye Hospital

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

Charles Retina Institute

Germantown, Tennessee, United States, 38138

United States, Texas

Texas Retina Associates

Dallas, Texas, United States, 75231

Retina Consultants of Texas

The Woodlands, Texas, United States, 77384

Sponsors and Collaborators

AbbVie

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT04832724
• Other Study ID Numbers: RGX-314-2103
• First Posted: April 6, 2021
• Last Update Posted: April 12, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AbbVie:

AMD; wet AMD; wAMD; neovascular AMD; nAMD; gene therapy

Additional relevant MeSH terms:

Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases