Pivotal 1 Study of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)

A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)

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 AMD; Wet Age-related Macular Degeneration; wAMD
• Intervention / Treatment: Genetic: RGX-314; Genetic: RGX-314; Biological: Ranibizumab (LUCENTIS®)

Detailed Description

This randomized, partially masked, controlled, Phase 2b/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 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 ranibizumab. Approximately 300 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2; Phase 3

Contacts and Locations

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

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Recruiting
      • Retinal Consultants of Arizona, Ltd.
    • Sun City, Arizona, United States, 85351
      • Recruiting
      • Barnet Dulaney Perkins Eye Center - Phoenix
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Retina-Vitreous Associates Medical Group
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Retina Vitreous Assoc Med Grp
    • Campbell, California, United States, 95008
      • Recruiting
      • Retinal Diagnostic Center
    • Encino, California, United States, 91436
      • Recruiting
      • The Retina Partners - Encino
    • Fullerton, California, United States, 92835
      • Recruiting
      • Retina Consultants of Orange County - Fullerton Office
    • Irvine, California, United States, 92697
      • Recruiting
      • University of California Irvine - School of Medicine - The Gavin Herbert Eye Institute
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Doheny Eye Institute - Doheny Eye Center - Arcadia
    • Mountain View, California, United States, 94040
      • Recruiting
      • Northern California Retina Vitreous Associates Medical Group, Inc. - Mountain View Office
    • Pasadena, California, United States, 91107
      • Recruiting
      • California Eye Specialists Medical Group Inc. - Pasadena
    • Poway, California, United States, 92064
      • Recruiting
      • Retina Consultants San Diego
    • Sacramento, California, United States, 95819
      • Recruiting
      • Retina Consultants
    • San Francisco, California, United States, 94109
      • Recruiting
      • West Coast Retina Medical Group - San Francisco Office
      • Contact: San Francisco 1 Location
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Medical Center - Retina and Vitreous Clinic
    • Santa Ana, California, United States, 92705
      • Recruiting
      • Orange County Retina Medical Group
    • Santa Barbara, California, United States, 85014
      • Recruiting
      • California Retina Consultants
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Recruiting
      • Retina Consultants of Southern Colorado PC- Colorado Springs
    • Durango, Colorado, United States, 81301
      • Recruiting
      • Southwest Retina Consultants
    • Lakewood, Colorado, United States, 80401
      • Recruiting
      • Colorado Retina Associates (CRA) - Red Rocks Medical Center Location
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Recruiting
      • Retina Group of New England - New London
  • Florida
    • Gainesville, Florida, United States, 32607
      • Recruiting
      • Vitreo Retinal Associates PA - The Millennium Center
    • Lakeland, Florida, United States, 33805-2908
      • Not yet recruiting
      • Florida Retina Consultants - Lakeland
    • Miami, Florida, United States, 33136
      • Recruiting
      • Bascom Palmer Eye Institute - University of Miami Health System
    • Pensacola, Florida, United States, 32503
      • Recruiting
      • Retina Specialty Institute - Pensacola
    • Saint Petersburg, Florida, United States, 33711
      • Recruiting
      • Retina Vitreous Associates of Florida (RVA) - Saint Petersburg
    • Tallahassee, Florida, United States, 32308
      • Not yet recruiting
      • Southern Vitreoretinal Associates, P.L.
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Active, not recruiting
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Recruiting
      • Georgia Retina PC - Marietta
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Recruiting
      • Retina Consultants of Hawaii (RCH) - Pali Momi Medical Center Location
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Illinois Eye and Ear Infirmary at UI Health UIC
    • Lemont, Illinois, United States, 60439
      • Recruiting
      • University Retina and Macula Associates, P.C. - Lemont Office
    • Oak Forest, Illinois, United States, 60452
      • Recruiting
      • University Retina and Macula Associates, PC - Oak Forest
    • Springfield, Illinois, United States, 62702
      • Not yet recruiting
      • Springfield Clinic
    • Springfield, Illinois, United States, 62703
      • Not yet 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 - New Albany
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Recruiting
      • Retina Associates, P.A. - Shawnee Mission
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • Recruiting
      • The Retina Care Center, LLC
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • The Johns Hopkins Hospital - Wilmer Eye Institute - East Baltimore
    • Hagerstown, Maryland, United States, 21740
      • Recruiting
      • Cumberland Valley Retina Consultants (CVRC)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Ophthalmic Consultants of Boston, Inc.
  • Michigan
    • Grand Blanc, Michigan, United States, 48439-8301
      • Not yet recruiting
      • Retina Associates of Michigan - Grand Blanc Office
    • Royal Oak, Michigan, United States, 48073
      • Recruiting
      • Associated Retinal Consultants P.C.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Recruiting
      • VitreoRetinal Surgery, PA - Edina Location
      • Contact: Location
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Minnesota
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Sierra Eye Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Recruiting
      • Eye Associates of New Mexico - Albuquerque - Retina Center Location
  • New York
    • Great Neck, New York, United States, 11021
      • Recruiting
      • Long Island Vitreoretinal Consultants - Great Neck
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Eye Center - Erwin Road - Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Not yet recruiting
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • Cincinnati Eye Institute - Blue Ash
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44130
      • Recruiting
      • Retina Associates of Cleveland, Inc. - Middleburg Heights Office
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Recruiting
      • Retina Vitreous Center (RVC)
  • Oregon
    • Portland, Oregon, United States, 97221
      • Recruiting
      • Retina Northwest, PC
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507-1429
      • Recruiting
      • Erie Retinal Surgery, Inc
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Mid Atlantic Retina - Philadelphia
  • South Carolina
    • Ladson, South Carolina, United States, 29456-4118
      • Recruiting
      • Charleston Neuroscience Institute
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Recruiting
      • Black Hills Regional Eye Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • Charles Retina Institute
  • Texas
    • Abilene, Texas, United States, 79606
      • Recruiting
      • West Texas Retina Consultants (WTRC) - Abilene Location
    • Austin, Texas, United States, 78705
      • Recruiting
      • Austin Research Center for Retina
    • Austin, Texas, United States, 78705
      • Recruiting
      • Austin Retina Associates
    • Austin, Texas, United States, 78750
      • Recruiting
      • Austin Clinical Research, LLC
    • Austin, Texas, United States, 78705
      • Recruiting
      • Retina Consultants of Austin
    • Burleson, Texas, United States, 79606
      • Recruiting
      • Star Retina
      • Contact: Burleson Location
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Texas Retina Associates
    • Fort Worth, Texas, United States, 76104
      • Not yet recruiting
      • Star Vision Consultants
    • San Antonio, Texas, United States, 78240-1657
      • Not yet recruiting
      • Retina Associates of South Texas, PA - San Antonio
    • San Antonio, Texas, United States, 78240-1657
      • Not yet recruiting
      • Retinal Consultants of San Antonio (Rcsa) - Medical Center
    • Southlake, Texas, United States, 76092
      • Recruiting
      • Retina Center of Texas - Southlake
    • The Woodlands, Texas, United States, 77030
      • Recruiting
      • Retina Consultants of Texas - The Woodlands
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Recruiting
      • Retina Associates of Utah, PC
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • John A. Moran Eye Center - University of Utah Health Care
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Recruiting
      • Wagner Macula & Retina Center
  • Washington
    • Bellevue, Washington, United States, 98004-3779
      • Recruiting
      • Pacific Northwest Retina
    • Silverdale, Washington, United States, 98383-7849
      • Recruiting
      • Retina Center Northwest - Silverdale
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin Health - University Station Clinic

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 in the study eye
5. Uncontrolled glaucoma in the study eye
6. History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1
7. 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.
8. Prior treatment with gene therapy.
9. Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

Study Plan

How is the study designed?

Design Details

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

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; AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1); Genetic: RGX-314; AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)
Experimental: RGX-314 Dose 2; RGX-314 Dose 2 administered via subretinal delivery one time.	Genetic: RGX-314; AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1); Genetic: RGX-314; AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)
Active Comparator: Control Arm; Ranibizumab administered via intravitreal injection approximately every 28 days	Biological: Ranibizumab (LUCENTIS®); 0.5 mg (0.05 mL of 10 mg/mL solution) administered by intravitreal injection approximately every 28 days; Other Names: Ranibizumab (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 adverse events (AEs)	Evaluate the safety and tolerability of RGX-314	Through Week 98
Mean change from baseline in BCVA	BCVA measured by ETDRS	At Week 98 (RGX-314 randomized participants only)
Mean change from baseline in Central Retinal Thickness (CRT) and Center Point Thickness (CPT) as measured by Spectral Domain Optical Coherence Tomography (SD-OCT)		At Week 54 and Week 98
Mean reduction in supplemental anti VEGF injection annualized rate compared with the prior 52 weeks preceding the first ranibizumab injection received as part of the Active Run-in Period (RGX 314 randomized participants)		Through Week 54 and Week 98
Mean supplemental anti-VEGF injection annualized rate in the RGX-314 arms		Through Week 54 and Week 98
Aqueous RGX-314 target protein (TP) concentrations		At Week 14, Week 26, Week 38, Week 54, and Week 98

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2020
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: January 8, 2021
• First Submitted That Met QC Criteria: January 8, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Eye Diseases; Ranibizumab; Antineoplastic Agents; Physiological Effects of Drugs; Gene therapy; 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; Ranibizumab
• Other Study ID Numbers: RGX-314-2104

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