Clinical trial NCT04832724: RGX-314 Gene Therapy Pharmacodynamic Study for Neovascular Age-related Macular Degeneration (nAMD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neovascular Age-related Macular Degeneration
Wet Macular Degeneration
Wet Age-related Macular Degeneration
Keywords: AMD
wet AMD
wAMD
neovascular AMD
nAMD
gene therapy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-04-06
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: RGX-314 target protein concentration in aqueous humor
timeFrame: At Week 24
Secondary outcomes:
measure: Incidence and severity of ocular Adverse Events (AEs) and overall AEs
timeFrame: Through Week 48
measure: Changes in Best Corrected Visual Acuity (BCVA)
timeFrame: At Week 24 and 48
measure: Changes in Central Retinal Thickness (CRT)
timeFrame: At Week 24 and 48
measure: Mean Supplemental anti-VEGF injection annualized rate through week 24 and week 48
timeFrame: Through Week 24 and week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Sun City
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: San Diego
country: United States
facility: Retina Consultants of San Diego
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: Philadelphia
country: United States
facility: Wills Eye Hospital
state: Pennsylvania
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
Study officials:
References: