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

Wet Age-related Macular Degeneration Clinical Trial

— ATMOSPHERE  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04704921
• Other study ID #: RGX-314-2104
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 29, 2020
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: AbbVie
• Contact: Patient Advocacy
• Phone: 1-866-860-0117
• Email: patientadvocacy[@]regenxbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 2026
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• AMD
• CNV
• Macular Degeneration
• nAMD
• wAMD
• Wet Age-related Macular Degeneration
• Wet AMD

Intervention

Genetic:
• RGX-314
AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)
• RGX-314
AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)

Biological:
• Ranibizumab (LUCENTIS®)
0.5 mg (0.05 mL of 10 mg/mL solution) administered by intravitreal injection approximately every 28 days

Locations

Country	Name	City	State
United States	Retina Consultants of Hawaii (RCH) - Pali Momi Medical Center Location	'Aiea	Hawaii
United States	West Texas Retina Consultants (WTRC) - Abilene Location	Abilene	Texas
United States	Eye Associates of New Mexico - Albuquerque - Retina Center Location	Albuquerque	New Mexico
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Clinical Research, LLC	Austin	Texas
United States	Austin Research Center for Retina	Austin	Texas
United States	Austin Retina Associates	Austin	Texas
United States	Retina Consultants of Austin	Austin	Texas
United States	The Johns Hopkins Hospital - Wilmer Eye Institute - East Baltimore	Baltimore	Maryland
United States	The Retina Care Center, LLC	Baltimore	Maryland
United States	Pacific Northwest Retina	Bellevue	Washington
United States	Retina Vitreous Assoc Med Grp	Beverly Hills	California
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Ophthalmic Consultants of Boston, Inc.	Boston	Massachusetts
United States	Star Retina	Burleson	Texas
United States	Retinal Diagnostic Center	Campbell	California
United States	Illinois Eye and Ear Infirmary at UI Health UIC	Chicago	Illinois
United States	Cincinnati Eye Institute - Blue Ash	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Retina Associates of Cleveland, Inc. - Middleburg Heights Office	Cleveland	Ohio
United States	Retina Consultants of Southern Colorado PC- Colorado Springs	Colorado Springs	Colorado
United States	Texas Retina Associates	Dallas	Texas
United States	Southwest Retina Consultants	Durango	Colorado
United States	Duke Eye Center - Erwin Road - Duke University Medical Center	Durham	North Carolina
United States	Retina Vitreous Center (RVC)	Edmond	Oklahoma
United States	The Retina Partners - Encino	Encino	California
United States	Erie Retinal Surgery, Inc	Erie	Pennsylvania
United States	Star Vision Consultants	Fort Worth	Texas
United States	Retina Consultants of Orange County - Fullerton Office	Fullerton	California
United States	Vitreo Retinal Associates PA - The Millennium Center	Gainesville	Florida
United States	Vitreoretinal Associates, P.A.	Gainesville	Florida
United States	Charles Retina Institute	Germantown	Tennessee
United States	Retina Associates of Michigan - Grand Blanc Office	Grand Blanc	Michigan
United States	Long Island Vitreoretinal Consultants - Great Neck	Great Neck	New York
United States	Cumberland Valley Retina Consultants (CVRC)	Hagerstown	Maryland
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	University of California Irvine - School of Medicine - The Gavin Herbert Eye Institute	Irvine	California
United States	Charleston Neuroscience Institute	Ladson	South Carolina
United States	Florida Retina Consultants - Lakeland	Lakeland	Florida
United States	Colorado Retina Associates (CRA) - Red Rocks Medical Center Location	Lakewood	Colorado
United States	University Retina and Macula Associates, P.C. - Lemont Office	Lemont	Illinois
United States	Doheny Eye Institute - Doheny Eye Center - Arcadia	Los Angeles	California
United States	University of Wisconsin Health - University Station Clinic	Madison	Wisconsin
United States	Georgia Retina PC - Marietta	Marietta	Georgia
United States	Bascom Palmer Eye Institute - University of Miami Health System	Miami	Florida
United States	VitreoRetinal Surgery, PA - Edina Location	Minneapolis	Minnesota
United States	Northern California Retina Vitreous Associates Medical Group, Inc. - Mountain View Office	Mountain View	California
United States	John-Kenyon American Eye Institute - New Albany	New Albany	Indiana
United States	University Retina and Macula Associates, PC - Oak Forest	Oak Forest	Illinois
United States	California Eye Specialists Medical Group Inc. - Pasadena	Pasadena	California
United States	Retina Specialty Institute - Pensacola	Pensacola	Florida
United States	Mid Atlantic Retina - Philadelphia	Philadelphia	Pennsylvania
United States	Retinal Consultants of Arizona, Ltd.	Phoenix	Arizona
United States	Retina Northwest, PC	Portland	Oregon
United States	Retina Consultants San Diego	Poway	California
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Sierra Eye Associates	Reno	Nevada
United States	Mayo Clinic - Minnesota	Rochester	Minnesota
United States	Associated Retinal Consultants P.C.	Royal Oak	Michigan
United States	Retina Consultants	Sacramento	California
United States	Retina Vitreous Associates of Florida (RVA) - Saint Petersburg	Saint Petersburg	Florida
United States	John A. Moran Eye Center - University of Utah Health Care	Salt Lake City	Utah
United States	Retina Associates of Utah, PC	Salt Lake City	Utah
United States	Retina Associates of South Texas, PA - San Antonio	San Antonio	Texas
United States	Retinal Consultants of San Antonio (RCSA) - Medical Center	San Antonio	Texas
United States	UCSF Medical Center - Retina and Vitreous Clinic	San Francisco	California
United States	West Coast Retina Medical Group - San Francisco Office	San Francisco	California
United States	Orange County Retina Medical Group	Santa Ana	California
United States	California Retina Consultants	Santa Barbara	California
United States	Retina Associates, P.A. - Shawnee Mission	Shawnee Mission	Kansas
United States	Retina Center Northwest - Silverdale	Silverdale	Washington
United States	Retina Center of Texas - Southlake	Southlake	Texas
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Barnet Dulaney Perkins Eye Center - Phoenix	Sun City	Arizona
United States	Southern Vitreoretinal Associates, P.L.	Tallahassee	Florida
United States	Retina Consultants of Texas - The Woodlands	The Woodlands	Texas
United States	Wagner Macula & Retina Center	Virginia Beach	Virginia
United States	Retina Group of New England - New London	Waterford	Connecticut
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change from baseline in Best Corrected Visual Acuity (BCVA)	BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)	At Week 54
Secondary	Incidences of ocular and overall adverse events (AEs)	Evaluate the safety and tolerability of RGX-314	Through Week 98
Secondary	Mean change from baseline in BCVA	BCVA measured by ETDRS	At Week 98 (RGX-314 randomized participants only)
Secondary	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
Secondary	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
Secondary	Mean supplemental anti-VEGF injection annualized rate in the RGX-314 arms		Through Week 54 and Week 98
Secondary	Aqueous RGX-314 target protein (TP) concentrations		At Week 14, Week 26, Week 38, Week 54, and Week 98