Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD (ASCENT)

A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD

RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. 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 intraocular injections, typically repeated every four to 12 weeks in frequency, 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.

Study Overview

• Status: Recruiting
• Conditions: CNV; AMD; nAMD; Wet Age-related Macular Degeneration; wAMD; WetAMD
• Intervention / Treatment: Genetic: RGX-314 Dose 1; Genetic: RGX-314 Dose 2; Biological: Aflibercept (EYLEA®)

Detailed Description

This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of RGX-314 relative to aflibercept. Approximately 465 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

• Study Type: Interventional
• Enrollment (Estimated): 465
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Patient Advocacy; Phone Number: +(1) 866-860-0117; Email: Patientadvocacy@regenxbio.com

Study Locations

• Canada
  • Québec, Canada, G1S 4L8
    • Recruiting
    • CHU de Quebec-Universite Laval
  • Alberta
    • Calgary, Alberta, Canada, T2H 0C8
      • Recruiting
      • Calgary Retina Consultants
    • Edmonton, Alberta, Canada, T5H 0X5
      • Recruiting
      • Alberta Retina Research Corporation
  • Ontario
    • Ottawa, Ontario, Canada, K2B 7E9
      • Recruiting
      • Retina Centre of Ottawa
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Recruiting
    • Emanuelli Research and Development Center
• United States
  • Arizona
    • Mesa, Arizona, United States, 85016
      • Recruiting
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85053
      • Recruiting
      • Retinal Research Institute
    • Phoenix, Arizona, United States, 85014
      • Recruiting
      • Retinal Consultants of Arizona
  • California
    • Bakersfield, California, United States, 93309
      • Recruiting
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Retina Vitreous Associates Medical Group
    • Campbell, California, United States, 95008
      • Recruiting
      • Retinal Diagnostic Center
    • Encino, California, United States, 91436
      • Recruiting
      • The Retina Partners
    • La Jolla, California, United States, 92093
      • Recruiting
      • UC San Diego
    • Poway, California, United States, 92064
      • Recruiting
      • Retina Consultants of San Diego
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis
    • Sacramento, California, United States, 85841
      • Recruiting
      • Retinal Consultants Medical Group, Inc
    • Santa Ana, California, United States, 92705
      • Recruiting
      • Orange County Retina Medical Group
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Recruiting
      • Retina Consultants of Southern Colorado P.C.
    • Durango, Colorado, United States, 81303
      • Recruiting
      • Southwest Retina Consultants
    • Lakewood, Colorado, United States, 80228
      • Recruiting
      • Colorado Retina Associates
    • Longmont, Colorado, United States, 80503
      • Recruiting
      • Eye Care Center of Northern Colorado
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Recruiting
      • National Ophthalmic Research Institute
    • Gainesville, Florida, United States, 32607
      • Recruiting
      • Vitreo Retinal Associates PA
    • Lakeland, Florida, United States, 33805
      • Recruiting
      • Florida Retina Consultants
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Florida Retina Institute
    • Pensacola, Florida, United States, 32503
      • Recruiting
      • Retina Specialty Institute
    • Pompano Beach, Florida, United States, 33064
      • Recruiting
      • Rand Eye Institute
    • Saint Petersburg, Florida, United States, 33711
      • Recruiting
      • Retina Vitreous Associates of Florida - Saint Petersburg
    • Winter Haven, Florida, United States, 33880
      • Recruiting
      • Center for Retina and Macular Disease
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Recruiting
      • Georgia Retina PC
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Recruiting
      • Retina Consultants of Hawaii
  • Illinois
    • Lemont, Illinois, United States, 60439
      • Recruiting
      • University Retina and Macula Associates, P.C.
    • Oak Forest, Illinois, United States, 60452
      • Recruiting
      • University Retina and Macula Associates, P.C.
    • Oak Park, Illinois, United States, 60304
      • Recruiting
      • Illinois Retina Associates
    • Springfield, Illinois, United States, 62702
      • Recruiting
      • Springfield Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Recruiting
      • Midwest Eye Institute
    • New Albany, Indiana, United States, 47150
      • Recruiting
      • John-Kenyon American Eye Institute
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Recruiting
      • Wolfe Eye Clinic
  • Maine
    • Portland, Maine, United States, 04101
      • Recruiting
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Wilmer Eye Institute
    • Baltimore, Maryland, United States, 21204
      • Recruiting
      • Retina Specialists
    • Hagerstown, Maryland, United States, 21740
      • Recruiting
      • Mid Atlantic Reina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts Eye and Ear Infirmary
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Ophthalmic Consultants of Boston, Inc
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • Recruiting
      • Retina Associates of Michigan
    • Novi, Michigan, United States, 48375
      • Recruiting
      • Associated Retinal Consultants
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Recruiting
      • Vitreo Retinal Surgery, PA
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Recruiting
      • Envision Ocular, LLC
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center - Harness Eye Institute
    • Rochester, New York, United States, 14620
      • Recruiting
      • Retina Associates of Western New York
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Recruiting
      • Western Carolina Retina Associates P.A.
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Eye Center
    • Hickory, North Carolina, United States, 28602
      • Recruiting
      • Greystone Eye
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44130
      • Recruiting
      • Retina Associates of Cleveland, Inc.
    • Cleveland, Ohio, United States, 44915
      • Recruiting
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43212
      • Recruiting
      • The Ohio State University Eye & Ear Institute
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Recruiting
      • Retina Vitreous Center Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Scheie Eye Institute
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Mid Atlantic Retina
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center
  • South Carolina
    • Beaufort, South Carolina, United States, 29902
      • Recruiting
      • Retina Consultants of Charleston
    • Charleston, South Carolina, United States, 29414
      • Recruiting
      • Retina Consulants of Charleston
    • Florence, South Carolina, United States, 29501
      • Recruiting
      • Palmetto Retina Center LLC
    • Ladson, South Carolina, United States, 29456
      • Recruiting
      • Retina Consultants of Charleston
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Recruiting
      • Southeastern Retina Associates
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • Charles Retina Institute
    • Johnson City, Tennessee, United States, 37604
      • Recruiting
      • Southeastern Retina Associates
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Retina Center Murfreesboro
  • Texas
    • Abilene, Texas, United States, 79606
      • Recruiting
      • West Texas Retina Consultants - Abilene
    • Abilene, Texas, United States, 79606-1224
      • Recruiting
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012
      • Recruiting
      • Texas Retina Associates
    • Austin, Texas, United States, 78750
      • Recruiting
      • Austin Clinical Research, LLC
    • Austin, Texas, United States, 78705
      • Recruiting
      • Retina Consultants of Austin
    • Bellaire, Texas, United States, 77401
      • Recruiting
      • Retina Consultants of Texas
    • Burleson, Texas, United States, 76028
      • Recruiting
      • Star Retina
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Texas Retina Associates
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Ophthalmology Surgery Center of Dallas
    • Round Rock, Texas, United States, 78681
      • Recruiting
      • Austin Retina Associates
    • San Antonio, Texas, United States, 78240
      • Recruiting
      • Retina Consultants of Texas
    • San Antonio, Texas, United States, 78240
      • Recruiting
      • Retina Associates of South Texas, P.A.
    • San Antonio, Texas, United States, 78251
      • Recruiting
      • Brown Retina Institute
    • Southlake, Texas, United States, 76092
      • Recruiting
      • Retina Center of Texas - Southlake
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Recruiting
      • Rocky Mountain Retina Consultants
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Recruiting
      • Piedmont Eye Center
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Wagner Macula & Retina Center
    • Richmond, Virginia, United States, 23235
      • Recruiting
      • Retina Institute of Virginia
  • Washington
    • Bellevue, Washington, United States, 98004
      • Recruiting
      • Vitreoretinal Associates of Washington
    • Bellevue, Washington, United States, 98004
      • Recruiting
      • Pacific Northwest Retina
    • Silverdale, Washington, United States, 98383
      • Recruiting
      • Retina Center Northwest
    • Spokane, Washington, United States, 99204
      • Recruiting
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 87 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 50 years and ≤ 89 years
2. An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye
3. Diagnosis of subfoveal CNV secondary to AMD in the study eye previously treated with anti-VEGF
4. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye.
5. Willing and able to provide written, signed informed consent for this study
6. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry

Exclusion Criteria:

1. CNV or macular edema in the study eye secondary to any causes other than AMD
2. Subfoveal fibrosis or atrophy in the study eye
3. Any condition in the investigator's opinion that could limit VA improvement in the study eye
4. Active or history of retinal detachment or current retinal tear in the study eye
5. Advanced glaucoma or history of secondary glaucoma in the study eye
6. Myocardial infarction, cerebrovascular accident, or transient ischemic attach within the past 6 months.
7. History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1
8. 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 Visit 1.
9. Prior treatment with gene therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RGX-314 Dose 1; RGX-314 Dose 1 administered via subretinal delivery one time.	Genetic: RGX-314 Dose 1; AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)
Experimental: RGX-314 Dose 2; RGX-314 Dose 2 administered via subretinal delivery one time.	Genetic: RGX-314 Dose 2; AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)
Active Comparator: Control Arm; Aflibercept administered via intravitreal injection approximately every 8 weeks	Biological: Aflibercept (EYLEA®); 2.0 mg (0.05 mLsolution) administered by intravitreal injection approximately every 8 weeks after 3 monthly injections Other Names: • Eylea (anti-VEGF agent)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in Best Corrected Visual Acuity (BCVA)	BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)	At Week 54

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidences of ocular and overall Serious Adverse Events (SAEs)	Incidences of ocular and overall Serious Adverse Events	At Week 54
Mean change from baseline in BCVA	BCVA measured by ETDRS	At Week 54 (RGX-314 randomized participants only)
Mean change from baseline in CRT and CPT as measured by SD-OCT	CRT and CPT as measured by SD-OCT	At Week 54 and Week 90
Mean reduction in supplemental anti VEGF injection annualized rate compared with the prior year of therapy	Supplemental anti-VEGF treatments required post therapy to the year prior	Through Week 54 and Week 108
Mean supplemental anti VEGF injection annualized rate in the RGX-314 arms	Supplemental anti-VEGF treatments required post therapy to the year prior	Through Week 54 and Week 108
Aqueous RGX-314 TP concentrations	Observation of concentration of RGX-314 in the aqueous humor over time	At Week 14, Week 38, Week 54, Week 74, Week 90 and Week 108

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2021
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: June 2, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; Eye Diseases; Ranibizumab; Antineoplastic Agents; Aflibercept; Physiological Effects of Drugs; Age-Related Macular Degeneration; Retinal Diseases; Macular Degeneration; Choroidal Neovascularization; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Anti-VEGF therapy; Retinal Degeneration; Wet Macular Degeneration; Neovascular Age-Related Macular Degeneration; Growth Substances; Growth Inhibitors; Anti-vascular endothelial grown factory therapy
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: RGX-314-3101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No