Clinical trial NCT04514653: RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Neovascular Age-Related Macular Degeneration (nAMD) (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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neovascular Age-Related Macular Degeneration (nAMD)
Keywords: AMD
wet AMD
wAMD
nAMD
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-08-17
Enrollment: 115
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the mean change in Best Corrected Visual Acuity (BCVA) for RGX-314 compared with ranibizumab monthly.
timeFrame: 40 weeks
Secondary outcomes:
measure: Evaluate the safety and tolerability of RGX-314
timeFrame: 52 weeks
measure: Evaluate the incidence of ocular inflammation following administration of RGX-314
timeFrame: 52 weeks
measure: Evaluate the effect of RGX-314 on choroidal neovascularization (CNV) lesion growth and leakage
timeFrame: 52 weeks
measure: Evaluate the effect of RGX-314 on BCVA
timeFrame: 52 weeks
measure: Evaluate the effect of RGX-314 on central retinal thickness (CRT)
timeFrame: 52 weeks
measure: Assess the need for supplemental anti-vascular endothelial growth factor (VEGF) therapy in participants who receive RGX-314 treatment
timeFrame: 52 weeks
measure: Evaluate the concentration of RGX-314 transgene product (TP) in aqueous humor and serum
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Location
state: Arizona
city: Bakersfield
country: United States
facility: Bakersfield Location
state: California
city: Beverly Hills
country: United States
facility: Beverly Hills Location
state: California
city: Mountain View
country: United States
facility: Mountain View Location
state: California
city: Poway
country: United States
facility: Poway Location
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Location
state: California
city: Augusta
country: United States
facility: Augusta Location
state: Georgia
city: Baltimore
country: United States
facility: Baltimore Location
state: Maryland
city: Boston
country: United States
facility: Boston Location
state: Massachusetts
city: Reno
country: United States
facility: Reno Location
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Location
state: New Mexico
city: Philadelphia
country: United States
facility: Philadelphia Location
state: Pennsylvania
city: Germantown
country: United States
facility: Germantown Location
state: Tennessee
city: Nashville
country: United States
facility: Nashville Location
state: Tennessee
city: The Woodlands
country: United States
facility: Woodlands Location
state: Texas
Study officials:
References: