Clinical trial NCT02462889: IAI Versus Sham as Prophylaxis Against Conversion to Neovascular AMD
Official title: A Prospective, Single-Blind, Randomized Study to Evaluate Intravitreal Aflibercept Injection (IAI) Versus Sham as PROphylaxis Against CONversion to Neovascular Age-Related Macular Degeneration (AMD) in High-Risk Eyes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Age-Related Macular Degeneration
Lead sponsor: Ophthalmic Consultants of Boston
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-06-04
Enrollment: 128
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a prospective, single-blind, randomized study to evaluate intravitreal aflibercept injection (IAI) versus sham as prophylaxis against conversion to neovascular age-related macular degeneration (AMD) in "high-risk" subjects.

Detailed description: 128 subjects will be enrolled in the trial and randomized in a 1:1 ratio to receive either IAI every three months for 24 months or sham injections. Enrollment will be stratified in order to ensure a balance between the two treatment groups for subjects who were diagnosed with exudative AMD within the past two years versus those diagnosed more than two years prior to Baseline.

Study assessments will be conducted at required visits every three months and include manifest refraction and ETDRS visual acuity testing, slit lamp exam and dilated fundus exam, spectral-domain optical coherence tomography (SD-OCT) using Avanti device, and OCT angiography using Avanti AngioVueTM, and fluorescein angiography. Fundus photography will also be performed at Baseline, Month 12 and Month 24 visits.

In the event of conversion to neovascular AMD in the study eye at any point during the study, the Investigator will treat the subject with IAI at a frequency per his/her discretion.

Eligibility criteria: Inclusion Criteria:

* Study eye must have a diagnosis of non-exudative age-related degeneration characterized by the presence of many intermediate sized drusen, 1 or more large drusen, and/or hyperpigmentary changes. Fellow (non-study) eye must have CNV lesion (i.e., leakage on fluorescein angiography and/or subretinal, intraretinal, or sub-RPE fluid on OCT) secondary to age-related macular degeneration OR history of CNV lesion secondary to age-related macular degeneration, as confirmed by current or past treatment or current or past diagnostic imaging.
* Subject must be willing and able to comply with clinic visits and study-related procedures.
* Subject must provide signed informed consent.
* Subject must be able to understand and complete study-related questionnaires. In order to participate in the home monitoring sub-study, subjects must have an approved wireless device (i.e. iPhone, iPad, or iPod running iOS 6.0 or later) or be willing to use a loaned device and have access to a wireless Internet connection for the duration of the study.

Exclusion Criteria:

* Evidence of neovascular AMD in the study eye at time of enrollment or anytime in the past. The reading center must confirm that there is no evidence of neovascular AMD in the study eye prior to enrollment.
* Serous PED of any size in the study eye, as determined by the reading center.
* Previous treatment with verteporfin PDT, anti-VEGF therapy, laser, external beam radiation or other AMD therapy in the study eye.
* History of macular hole in study eye.
* History of vitrectomy in study eye.
* Lens extraction or implantation within the last 3 months.
* Capsulotomy within the last 1 month.
* Lens or other media opacity that would preclude good fundus photography or angiography within the next 2 years.
* Macular edema or signs of diabetic retinopathy more severe than 10 red dots (microaneurysms or blot hemorrhages).
* Retinal changes related to high myopia and/or myopic correction greater than 8.00 diopters spherical equivalent.
* Any progressive ocular disease that would affect visual acuity within the next 2 years.
* Previous participation in any studies of investigational drugs likely to have ocular effects within 30 days preceding the initial study treatment.
* Concurrent use of systemic anti-VEGF agents.
* Active or recent (within 4 weeks) intraocular inflammation (grade trace or above) in the study eye.
* Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
* For subjects who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed 8 diopters of myopia.
* Uncontrolled glaucoma in the study eye (defined as intraocular pressure greater than 25 mmHg) despite treatment with anti-glaucoma medication).
* Subjects who are unable to be photographed to document CNV due to known allergy to fluorescein dye, lack of venous access or cataract obscuring the CNV.
* Subjects with other ocular diseases that can compromise the visual acuity of the study eye such as amblyopia and anterior ischemic optic neuropathy.
* Current treatment for active systemic infection.
* Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders.
* History of recurrent significant infections or bacterial infections.
* Inability to comply with study or follow-up procedures.
* Pregnancy (positive pregnancy test) or lactation

Primary outcomes:
measure: Proportion of subjects converting to neovascular AMD at 24 months, characterized by the development of choroidal neovascularization (CNV).
timeFrame: 24 months
Secondary outcomes:
measure: Mean change in visual acuity at 24 months compared to baseline
timeFrame: 24 months
measure: Percentage of subjects losing less than 15 ETDRS letters at 24 months compared to baseline
timeFrame: 24 months
measure: Incidence and severity of potential ocular side effects including endophthamitis, retinal detachment, cataract, and intraocular inflammation
timeFrame: up to Month 24
measure: Incidence and severity of systemic side effects
timeFrame: up to Month 24
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Edison
country: United States
facility: NJ Retina
state: New Jersey
city: Houston
country: United States
facility: Retina Consultants of Houston
state: Texas
Study officials:
affiliation: Ophthalmic Consultants of Boston
name: Jeffrey S Heier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heier JS, Brown DM, Shah SP, Saroj N, Dang S, Waheed NK, Wykoff CC, Prenner JL, Boyer DS. Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes: A Randomized Clinical Trial. JAMA Ophthalmol. 2021 May 1;139(5):542-547. doi: 10.1001/jamaophthalmol.2021.0221.