Clinical trial NCT03748784: ADVM-022 Intravitreal Gene Therapy for Wet AMD
Official title: An Open Label Phase 1 Study of ADVM-022 (AAV.7m8-aflibercept) in Neovascular (Wet) Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Wet Age-related Macular Degeneration
Neovascular Age-related Macular Degeneration
Keywords: Choroidal Neovascularizatio
ADVM-022
CNV
ADVM-022-01
AAV.7m8
Anti-VEGF therapy
Blindness
Gene therapy
Aflibercept (Eylea)
Age-Related Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
AAV Vector
Adverum
wAMD
AMD
wet AMD
Lead sponsor: Adverum Biotechnologies, Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-21
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open-label, dose-ranging clinical study to evaluate the safety and tolerability of ADVM-022 in subjects with wet AMD.
Primary purpose: TREATMENT

Brief summary: ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition and the leading cause of blindness in the elderly. The available therapies for treating wet AMD require life-long intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A one-time IVT administration of ADVM-022 has the potential to treat wet AMD by providing durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and maintaining the vision of patients. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with wet AMD receiving anti-VEGF therapy in clinical practice.

Detailed description: This open-label, multicenter, dose-ranging study will evaluate 2 dose levels in up to 30 subjects (15 per dose) with active choroidal neovascularization (CNV) secondary to AMD. Subjects who are under active anti-VEGF treatment and have demonstrated a meaningful response to anti-VEGF therapy will be considered for participation in this study. The primary endpoint for this study is safety and tolerability of ADVM-022. All subjects will continue to be assessed for 104 weeks following treatment with ADVM-022.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 50
* Diagnosis of neovascular (wet) AMD
* BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320 for each cohort
* Subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2 injections within 4 months prior to screening
* Demonstrated a meaningful response to anti-VEGF therapy
* Willing and able to provide consent

Exclusion Criteria:

* History of retinal disease in the study eye other than wet AMD
* Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement
* History of retinal detachment (with or without repair) in the study eye
* History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye
* Uncontrolled glaucoma in the study eye
* Any prior treatment with photodynamic therapy or retinal laser for the treatment of wet AMD and any previous therapeutic radiation in the region of the study eye
* Any previous intraocular or periocular surgery on the study eye within 6 months
* Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months
* Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg

Primary outcomes:
measure: Type, severity, and incidence of ocular and systemic adverse events (AEs)
timeFrame: 104 weeks
Secondary outcomes:
measure: Change in best corrected visual acuity (BCVA)
timeFrame: 104 weeks
measure: Change in central subfield thickness (CST) and macular volume measured by SD-OCT
timeFrame: 104 weeks
measure: Percentage of subjects requiring anti-VEGF injections over time
timeFrame: 104 weeks
measure: Mean number of anti-VEGF injections over time
timeFrame: 104 weeks
measure: Percentage of subjects without intraretinal fluid over time
timeFrame: 104 weeks
measure: Percentage of subjects without subretinal fluid over time
timeFrame: 104 weeks
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Adverum Clinical Site
state: California
city: Beverly Hills
country: United States
facility: Adverum Clinical Site
state: California
city: Golden
country: United States
facility: Adverum Clinical Site
state: Colorado
city: Deerfield Beach
country: United States
facility: Adverum Clinical Site
state: Florida
city: Reno
country: United States
facility: Adverum Clinical Site
state: Nevada
city: Philadelphia
country: United States
facility: Adverum Clinical Site
state: Pennsylvania
city: West Columbia
country: United States
facility: Adverum Clinical Site
state: South Carolina
city: Nashville
country: United States
facility: Adverum Clinical Site
state: Tennessee
city: Abilene
country: United States
facility: Adverum Clinical Site
state: Texas
city: Houston
country: United States
facility: Adverum Clinical Site
state: Texas
city: The Woodlands
country: United States
facility: Adverum Clinical Site
state: Texas
Study officials:
affiliation: Adverum Biotechnologies, Inc.
name: OPTIC Medical Monitor
role: STUDY_CHAIR
References: