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

Tracking Information

• First Submitted Date: March 30, 2021
• First Posted Date: April 6, 2021
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: February 22, 2021
• Actual Primary Completion Date: October 2, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 1, 2021): RGX-314 target protein concentration in aqueous humor [ Time Frame: At Week 24 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2021)

• Incidence and severity of ocular Adverse Events (AEs) and overall AEs [ Time Frame: Through Week 48 ]
  Evaluate the safety and tolerability of RGX-314
• Changes in Best Corrected Visual Acuity (BCVA) [ Time Frame: At Week 24 and 48 ]
  BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
• Changes in Central Retinal Thickness (CRT) [ Time Frame: 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 [ Time Frame: Through Week 24 and week 48 ]
  To assess the need for supplemental anti-VEGF therapy over 48 weeks

Original Secondary Outcome Measures (submitted: April 1, 2021)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Study Arms

• Experimental: Commercial Formulation Dose 1
  Dose 1 of RGX-314
  Intervention: Genetic: RGX-314
• Experimental: Clinical Formulation Dose 1
  Dose 1 of RGX-314
  Intervention: Genetic: RGX-314
• Experimental: Commercial Formulation Dose 2
  Dose 2 of RGX-314
  Intervention: Genetic: RGX-314
• Experimental: Clinical Formulation Dose 2
  Dose 2 of RGX-314
  Intervention: Genetic: RGX-314

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 1, 2021): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 18, 2024
• Actual Primary Completion Date: October 2, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 89 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04832724
• Other Study ID Numbers: RGX-314-2103
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: REGENXBIO Inc.
• Current Study Sponsor: AbbVie
• Original Study Sponsor: REGENXBIO Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AbbVie
• Verification Date: April 2024