Safety and Tolerability of RGX-314 Gene Therapy for Neovascular AMD Trial

• Sponsor: REGENXBIO, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03066258
• Collaborator: (none)
• Enrollment: 42
• Locations: 8
• Arms: 5
• Anticipated Duration (Months): 49
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Excessive vascular endothelial growth factor (VEGF) plays a key part in promoting neovascularization and edema in neovascular (wet) age-related macular degeneration (nAMD). VEGF inhibitors (anti-VEGF), including ranibizumab (LUCENTIS®, Genentech) and aflibercept (EYLEA®, Regeneron), have been shown to be safe and effective for treating nAMD and have demonstrated improvement in vision. However, anti-VEGF therapy is administered frequently via intravitreal injection and can be a significant burden to the patients. RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein. The long-term, stable delivery of this therapeutic protein following a 1 time gene therapy treatment for nAMD could potentially reduce the treatment burden of currently available therapies while maintaining vision with a favorable benefit:risk profile.

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration; Wet Age-related Macular Degeneration	Genetic: RGX-314	Phase 1/Phase 2

Detailed Description

This Phase I/IIa, open-label, multiple-cohort, dose-escalation study is designed to evaluate the safety and tolerability of RGX-314 gene therapy in subjects with previously treated nAMD. Five doses will be studied in approximately 42 subjects. Subjects who meet the inclusion/exclusion criteria and have an anatomic response to an initial anti VEGF injection will receive a single dose of RGX-314 administered by subretinal delivery. RGX-314 uses an AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds to and neutralizes VEGF activity. Safety will be the primary focus for the initial 24 weeks after RGX-314 administration (primary study period). Following completion of the primary study period, subjects will continue to be assessed until 104 weeks following treatment with RGX-314.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: dose escalationdose escalation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/IIa, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With RGX-314 in Subjects With Neovascular AMD (nAMD)
• Actual Study Start Date: Mar 31, 2017
• Actual Primary Completion Date: Nov 24, 2019
• Anticipated Study Completion Date: May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose 1 3E9 GC/eye of RGX-314	Genetic: RGX-314; RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Dose 2 1E10 GC/eye of RGX-314	Genetic: RGX-314; RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Dose 3 6E10 GC/eye of RGX-314	Genetic: RGX-314; RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Dose 4 1.6E11 GC/eye of RGX-314	Genetic: RGX-314; RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Dose 5 2.5E11 GC/eye of RGX-314	Genetic: RGX-314; RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein

Outcome Measures

Primary Outcome Measures

1. Safety (incidence of ocular and non-ocular AEs and SAEs) [26 weeks]

   incidence of ocular and non-ocular AEs and SAEs

Secondary Outcome Measures

1. Safety (incidence of ocular and non-ocular AEs and SAEs) [106 weeks]

   incidence of ocular and non-ocular AEs and SAEs

2. Change in best corrected visual acuity [106 weeks]

   BCVA

3. Change in central retinal thickness [106 weeks]

   CRT as measured by SD-OCT

4. Rescue injections (Mean number of rescue injections) [106 weeks]

   Mean number of rescue injections

5. Mean change in area of CNV [106 weeks]

   Area of CNV and leakage measured by FA

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients ≥ 50 and ≤ 89 years with a diagnosis of subfoveal CNV secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy.

2. BCVA between ≤20/63 and ≥20/400 (≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400 (≤73 and ≥19 ETDRS letters) for the rest of the cohort.

3. History of need for and response to anti-VEGF therapy.

4. Response to anti-VEGF at trial entry (assessed by SD-OCT at week 1)

5. Must be pseudophakic (status post cataract surgery) in the study eye.

6. AST/ALT < 2.5 × ULN; TB < 1.5 × ULN; PT < 1.5 × ULN; Hb > 10 g/dL (males) and > 9 g/dL (females); Platelets > 100 × 10^{3/µL; eGFR > 30 mL/min/1.73 m}2

7. Must be willing and able to provide written, signed informed consent.

Exclusion Criteria:

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

2. Any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea.

3. Active or history of retinal detachment in the study eye.

4. Advanced glaucoma in the study eye.

5. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening.

6. Presence of an implant in the study eye at screening (excluding intraocular lens).

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

8. Uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Santa Barbara location	Santa Barbara	California	United States	93103
2	Baltimore location	Baltimore	Maryland	United States	21287
3	Boston location	Boston	Massachusetts	United States	02114
4	Reno location	Reno	Nevada	United States	89502
5	Philadelphia location 1	Philadelphia	Pennsylvania	United States	19104
6	Philadelphia location 2	Philadelphia	Pennsylvania	United States	19107
7	Memphis location	Germantown	Tennessee	United States	38138
8	Houston location	Houston	Texas	United States	77030

Sponsors and Collaborators

• REGENXBIO, Inc.

Investigators

• Principal Investigator: Jeffrey Heier, MD, Ophthalmic Consultants of Boston

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: REGENXBIO, Inc.
• ClinicalTrials.gov Identifier: NCT03066258
• Other Study ID Numbers: RGX-314-001
• First Posted: Feb 28, 2017
• Last Update Posted: Apr 2, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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 REGENXBIO, Inc.: nAMD; wet AMD; gene therapy
• Additional relevant MeSH terms: Macular Degeneration

Study Results

No Results Posted as of Apr 2, 2021