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

Wet Age-related Macular Degeneration Clinical Trial

— ASCENT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05407636
• Other study ID #: RGX-314-3101
• Status: Recruiting
• Phase: Phase 3
• Start date: December 28, 2021
• Est. completion date: December 2025

Study information

• Verified date: August 2023
• 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 465
• Est. completion date: December 2025
• Est. primary completion date: February 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 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.

Related Conditions & MeSH terms

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

Intervention

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

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)

Locations

Country	Name	City	State
Canada	Calgary Retina Consultants	Calgary	Alberta
Canada	Alberta Retina Research Corporation	Edmonton	Alberta
Canada	Retina Centre of Ottawa	Ottawa	Ontario
Canada	CHU de Quebec-Universite Laval	Québec
Puerto Rico	Emanuelli Research and Development Center	Arecibo
United States	Retina Consultants of Hawaii	'Aiea	Hawaii
United States	Retina Research Institute of Texas	Abilene	Texas
United States	West Texas Retina Consultants - Abilene	Abilene	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Western Carolina Retina Associates P.A.	Asheville	North Carolina
United States	Austin Clinical Research, LLC	Austin	Texas
United States	Retina Consultants of Austin	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Johns Hopkins University	Baltimore	Maryland
United States	Retina Specialists	Baltimore	Maryland
United States	Wilmer Eye Institute	Baltimore	Maryland
United States	Retina Consultants of Charleston	Beaufort	South Carolina
United States	Retina Consultants of Texas	Bellaire	Texas
United States	Pacific Northwest Retina	Bellevue	Washington
United States	Vitreoretinal Associates of Washington	Bellevue	Washington
United States	Retina Vitreous Associates Medical Group	Beverly Hills	California
United States	Envision Ocular, LLC	Bloomfield	New Jersey
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston, Inc	Boston	Massachusetts
United States	Star Retina	Burleson	Texas
United States	Retinal Diagnostic Center	Campbell	California
United States	Retina Consulants of Charleston	Charleston	South Carolina
United States	Southeastern Retina Associates	Chattanooga	Tennessee
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Retina Associates of Cleveland, Inc.	Cleveland	Ohio
United States	Retina Consultants of Southern Colorado P.C.	Colorado Springs	Colorado
United States	The Ohio State University Eye & Ear Institute	Columbus	Ohio
United States	Ophthalmology Surgery Center of Dallas	Dallas	Texas
United States	Texas Retina Associates	Dallas	Texas
United States	Southwest Retina Consultants	Durango	Colorado
United States	Duke Eye Center	Durham	North Carolina
United States	Vitreo Retinal Surgery, PA	Edina	Minnesota
United States	Retina Vitreous Center Research	Edmond	Oklahoma
United States	The Retina Partners	Encino	California
United States	Palmetto Retina Center LLC	Florence	South Carolina
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Vitreo Retinal Associates PA	Gainesville	Florida
United States	Charles Retina Institute	Germantown	Tennessee
United States	Retina Associates of Michigan	Grand Blanc	Michigan
United States	Mid Atlantic Reina Specialists	Hagerstown	Maryland
United States	Greystone Eye	Hickory	North Carolina
United States	MidWest Eye Institute	Indianapolis	Indiana
United States	Southeastern Retina Associates	Johnson City	Tennessee
United States	UC San Diego	La Jolla	California
United States	Retina Consultants of Charleston	Ladson	South Carolina
United States	Florida Retina Consultants	Lakeland	Florida
United States	Colorado Retina Associates	Lakewood	Colorado
United States	University Retina and Macula Associates, P.C.	Lemont	Illinois
United States	Eye Care Center of Northern Colorado	Longmont	Colorado
United States	Piedmont Eye Center	Lynchburg	Virginia
United States	Georgia Retina PC	Marietta	Georgia
United States	Barnet Dulaney Perkins Eye Center	Mesa	Arizona
United States	Tennessee Retina Center Murfreesboro	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	John-Kenyon American Eye Institute	New Albany	Indiana
United States	Columbia University Irving Medical Center - Harness Eye Institute	New York	New York
United States	Wagner Macula & Retina Center	Norfolk	Virginia
United States	Associated Retinal Consultants	Novi	Michigan
United States	University Retina and Macula Associates, P.C.	Oak Forest	Illinois
United States	Illinois Retina Associates	Oak Park	Illinois
United States	Florida Retina Institute	Orlando	Florida
United States	Retina Specialty Institute	Pensacola	Florida
United States	Mid Atlantic Retina	Philadelphia	Pennsylvania
United States	Scheie Eye Institute	Philadelphia	Pennsylvania
United States	Retinal Consultants of Arizona	Phoenix	Arizona
United States	Retinal Research Institute	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rand Eye Institute	Pompano Beach	Florida
United States	Maine Eye Center	Portland	Maine
United States	Retina Consultants of San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Retina Associates of Western New York	Rochester	New York
United States	Austin Retina Associates	Round Rock	Texas
United States	Retinal Consultants Medical Group, Inc	Sacramento	California
United States	UC Davis	Sacramento	California
United States	Retina Vitreous Associates of Florida - Saint Petersburg	Saint Petersburg	Florida
United States	Rocky Mountain Retina Consultants	Salt Lake City	Utah
United States	Brown Retina Institute	San Antonio	Texas
United States	Retina Associates of South Texas, P.A.	San Antonio	Texas
United States	Retina Consultants of Texas	San Antonio	Texas
United States	Orange County Retina Medical Group	Santa Ana	California
United States	Retina Center Northwest	Silverdale	Washington
United States	Retina Center of Texas - Southlake	Southlake	Texas
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Springfield Clinic	Springfield	Illinois
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

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 Serious Adverse Events (SAEs)	Incidences of ocular and overall Serious Adverse Events	At Week 54
Secondary	Mean change from baseline in BCVA	BCVA measured by ETDRS	At Week 54 (RGX-314 randomized participants only)
Secondary	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
Secondary	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
Secondary	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
Secondary	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