RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Neovascular Age-Related Macular Degeneration (nAMD)

Neovascular Age-Related Macular Degeneration (nAMD) Clinical Trial

— AAVIATE  

Official title:

A Phase 2, Randomized, Dose-escalation, Ranibizumab-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via One or Two Suprachoroidal Space (SCS) Injections in Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04514653
• Other study ID #: RGX-314-2102
• Status: Recruiting
• Phase: Phase 2
• Start date: August 25, 2020
• Est. completion date: January 2024

Study information

• Verified date: May 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 potential novel one-time gene therapy treatment 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 twelve 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.

Description:

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of RGX-314 gene therapy in subjects with nAMD. Approximately 115 participants who meet the inclusion/exclusion criteria will be enrolled into one of 6 cohorts. Participants will be randomized in Cohorts 1 and 2 to receive RGX-314 or ranibizumab control, and participants enrolled in Cohorts 3 through 5 will receive RGX-314. Participants enrolled in Cohort 6 will receive RGX-314 and will be randomized to one of two different post-procedural steroid regimens. Cohort 1 will evaluate RGX-314 Dose 1, Cohorts 2 and 3 will evaluate RGX-314 Dose 2, and Cohorts 4, 5, and 6 will evaluate RGX-314 Dose 3. Participants will be evaluated for efficacy, safety and tolerability of RGX-314 throughout the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: January 2024
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 89 Years

Eligibility

Inclusion Criteria:

• Age >/= 50 and </= 89
• Diagnosis of CNV secondary to age-related macular degeneration in the study eye.
• Participants must have demonstrated a meaningful response to anti-VEGF therapy.
• Willing and able to provide written, signed informed consent for this study.

Exclusion Criteria:

• CNV or macular edema in the study eye secondary to any causes other than AMD.
• Subfoveal fibrosis or atrophy in study eye.
• Participants who have had a prior vitrectomy.
• Active or history of retinal detachment in the study eye.
• History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product (IP), other than anti-VEGF therapy, in the 6 months prior to study entry.
• Received any gene therapy.
• Any condition preventing visualization of the fundus or VA improvement in the study eye, eg, cataract.
• History of intraocular surgery in the study eye within 12 weeks of study entry.
• Receipt of any IP within 30 days of study entry or 5 half-lives of the IP.
• Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within 6 months of study entry.
• Cohorts 1 - 5 only: Uncontrolled glaucoma in the study eye.
• COHORT 6 ONLY:
• Active or history of glaucoma or ocular hypertension in the study eye.
• Certain OCT characteristics including: Large Pigment Epithelial Detachments (PED), clinically significant Epiretinal Membrane (ERM) in the study eye at Visit 1. Note: Other inclusion/exclusion criteria apply.

Related Conditions & MeSH terms

• Choroidal Effusions
• Macular Degeneration
• Neovascular Age-Related Macular Degeneration (nAMD)
• Wet Macular Degeneration

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:
• Ranibizumab
Ranibizumab (anti-VEGF agent)

Genetic:
• RGX-314 Dose 3
AAV8 vector containing a transgene for anti-VEGF fab (Dose 3)

Drug:
• Local steroid
Local Steroid
• Topical steroid
Topical steroid

Locations

Country	Name	City	State
United States	Albuquerque Location	Albuquerque	New Mexico
United States	Augusta Location	Augusta	Georgia
United States	Bakersfield Location	Bakersfield	California
United States	Baltimore Location	Baltimore	Maryland
United States	Beverly Hills Location	Beverly Hills	California
United States	Boston Location	Boston	Massachusetts
United States	Germantown Location	Germantown	Tennessee
United States	Mountain View Location	Mountain View	California
United States	Nashville Location	Nashville	Tennessee
United States	Philadelphia Location	Philadelphia	Pennsylvania
United States	Phoenix Location	Phoenix	Arizona
United States	Poway Location	Poway	California
United States	Reno Location	Reno	Nevada
United States	Santa Barbara Location	Santa Barbara	California
United States	Woodlands Location	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the mean change in Best Corrected Visual Acuity (BCVA) for RGX-314 compared with ranibizumab monthly.	The scale used is the early treatment diabetic retinopathy study (ETDRS) letter score from 0-100 and higher score being better vision.	40 weeks
Secondary	Evaluate the safety and tolerability of RGX-314	Incidence of overall and ocular adverse events (AEs) and serious adverse events (SAEs)	52 weeks
Secondary	Evaluate the incidence of ocular inflammation following administration of RGX-314	Proportion of participants who experience ocular inflammation following SCS RGX-314 administration	52 weeks
Secondary	Evaluate the effect of RGX-314 on choroidal neovascularization (CNV) lesion growth and leakage	Mean change from baseline in CNV lesion size and leakage area based on fluorescein angiography (FA) at Week 52.	52 weeks
Secondary	Evaluate the effect of RGX-314 on BCVA	Mean change from baseline in BCVA to Week 52	52 weeks
Secondary	Evaluate the effect of RGX-314 on central retinal thickness (CRT)	Mean change from baseline in CRT as measured by spectral domain-optical coherence tomography (SD-OCT) to Week 40 and Week 52	52 weeks
Secondary	Assess the need for supplemental anti-vascular endothelial growth factor (VEGF) therapy in participants who receive RGX-314 treatment	Mean supplemental anti-VEGF injection annualized rate in the RGX-314 treatment arm through Week 40 and Week 52	52 weeks
Secondary	Evaluate the concentration of RGX-314 transgene product (TP) in aqueous humor and serum	Mean change from baseline and Week 54 in serum RGX-314 TP concentration over time	52 weeks