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CompletedNCT02462889PRO-CONUpdated Nov 14, 2025Results posted

IAI Versus Sham as Prophylaxis Against Conversion to Neovascular AMD

A Phase 2 interventional study of Intravitreal aflibercept injection and Placebo in Age-Related Macular Degeneration, sponsored by Jeffrey S Heier. Completed at 4 sites in United States. Per ClinicalTrials.gov, last updated 2025-11-14.

Sponsored by Jeffrey S Heier · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
128
Allocation
Randomized
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Age-Related Macular Degeneration
03

In context

Macular Degeneration

1,473 studies on the registry are indexed under Macular Degeneration; 206 are open to participants now.

This study's enrollment of 128 is above the median of 51 across 984 interventional studies indexed under Macular Degeneration.

Browse Macular Degeneration studies →

Lead sponsor

Jeffrey S Heier is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
128 participants (actual)

Study arms

  • Experimental
    Intravitreal aflibercept injection

    Subjects will be randomized to receive intravitreal aflibercept injection every three months for 24 months.

    Drug: Intravitreal aflibercept injection

  • Placebo comparator
    Placebo

    Subjects will be randomized to receive sham injection every three months for 24 months.

    Drug: Placebo

Interventions

  • DrugIntravitreal aflibercept injection

    Intravitreal aflibercept injection

    Also known as: Eylea

  • DrugPlacebo

    Sham injection

    Also known as: Sham injection

06

What researchers measure

Primary outcomes

  1. Percentage of Subjects Converting to Exudative AMD at 24 Months.

    Percentage of subjects converting to exudative AMD at 24 months as confirmed by independent masked reading center.

    Time frame: 24 months

Secondary outcomes

  1. Percentage of Patients Converted to Exudative AMD Who Had Exudative AMD in Fellow Eye ≤ 2 Years at Baseline.

    Percentage of patients converted to exudative AMD in study eye who had exudative AMD in fellow eye ≤ 2 years at Baseline.

    Time frame: up to Month 24

  2. Percentage of Patient Converted to Exudative AMD Based on Presence of Nonexudative CNV.

    Percentage of patients converted to exudative AMD compared to all patients with presence of nonexudative CNV in the study eye at Month 24, as confirmed by independent reading center evaluation of OCT angiography images.

    Time frame: up to Month 24

  3. Mean Change in Best-corrected Visual Acuity at 24 Months Compared to Baseline

    Mean change in best-corrected visual acuity (BCVA) at 24 months compared to baseline according to ETDRS protocol. BCVA is evaluated by counting the number of letters correctly read by the patient on an ETDRS eye chart. A higher value indicates that the patient read more letter correctly which indicates a better outcome.

    Time frame: 24 months

  4. Mean Change in Growth of Geographic Atrophy.

    Mean change in growth of geographic atrophy from baseline to Month 24.

    Time frame: 24 months

07

Results

Posted Nov 14, 2025
Limitations and caveats
No limitations. Trial was completed as planned.

Participant flow

Participant flow — Overall Study
MilestoneIntravitreal aflibercept injectionPlacebo
Started6364
Completed6053
Not completed311
Withdrew: Withdrawal by subject26
Withdrew: Death15

Outcome measures

PrimaryPercentage of Subjects Converting to Exudative AMD at 24 Months.

Percentage of subjects converting to exudative AMD at 24 months as confirmed by independent masked reading center.

Time frame:
24 months
Reported as:
Count of participants · Participants
Percentage of Subjects Converting to Exudative AMD at 24 Months.
ParticipantsIntravitreal aflibercept injectionPlacebo
Percentage of Subjects Converting to Exudative AMD at 24 Months.67
SecondaryPercentage of Patients Converted to Exudative AMD Who Had Exudative AMD in Fellow Eye ≤ 2 Years at Baseline.

Percentage of patients converted to exudative AMD in study eye who had exudative AMD in fellow eye ≤ 2 years at Baseline.

Time frame:
up to Month 24
Reported as:
Count of participants · Participants
Percentage of Patients Converted to Exudative AMD Who Had Exudative AMD in Fellow Eye ≤ 2 Years at Baseline.
ParticipantsIntravitreal Aflibercept InjectionPlacebo
Percentage of Patients Converted to Exudative AMD Who Had Exudative AMD in Fellow Eye ≤ 2 Years at Baseline.45
SecondaryPercentage of Patient Converted to Exudative AMD Based on Presence of Nonexudative CNV.

Percentage of patients converted to exudative AMD compared to all patients with presence of nonexudative CNV in the study eye at Month 24, as confirmed by independent reading center evaluation of OCT angiography images.

Time frame:
up to Month 24
Reported as:
Count of participants · Participants
Percentage of Patient Converted to Exudative AMD Based on Presence of Nonexudative CNV.
ParticipantsIntravitreal aflibercept injectionPlacebo
Percentage of Patient Converted to Exudative AMD Based on Presence of Nonexudative CNV.34
SecondaryMean Change in Best-corrected Visual Acuity at 24 Months Compared to Baseline

Mean change in best-corrected visual acuity (BCVA) at 24 months compared to baseline according to ETDRS protocol. BCVA is evaluated by counting the number of letters correctly read by the patient on an ETDRS eye chart. A higher value indicates that the patient read more letter correctly which indicates a better outcome.

Time frame:
24 months
Reported as:
Mean · number of letters read on eye chart
Mean Change in Best-corrected Visual Acuity at 24 Months Compared to Baseline
number of letters read on eye chartIntravitreal aflibercept injectionPlacebo
Mean Change in Best-corrected Visual Acuity at 24 Months Compared to Baseline2.8 (0.70 to 6.64)0.2 (-4.39 to 2.52)
SecondaryMean Change in Growth of Geographic Atrophy.

Mean change in growth of geographic atrophy from baseline to Month 24.

Time frame:
24 months
Reported as:
Mean · millimeters squared
Mean Change in Growth of Geographic Atrophy.
millimeters squaredIntravitreal aflibercept injectionPlacebo
Mean Change in Growth of Geographic Atrophy.0.34 (-0.07 to 0.36)0.43 (0.11 to 0.96)

Adverse events

Collected over 2 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intravitreal aflibercept injection1/63 (1.6%)14/63 (22.2%)9/63 (14.3%)
Placebo5/64 (7.8%)27/64 (42.2%)8/64 (12.5%)
Most frequent serious events
Showing 10 of 29
Most frequent serious events
EventIntravitreal aflibercept injectionPlacebo
PneumoniaRespiratory, thoracic and mediastinal disorders4/632/64
CVAVascular disorders1/633/64
Internal bleedingGastrointestinal disorders0/632/64
Blood loss from fall requiring transfusionSkin and subcutaneous tissue disorders1/630/64
Carcinoma in situ of the vulvaSkin and subcutaneous tissue disorders1/630/64
CellulitisSkin and subcutaneous tissue disorders1/631/64
Fractured femurMusculoskeletal and connective tissue disorders1/631/64
Hip replacementMusculoskeletal and connective tissue disorders1/631/64
Irregular heartbeatCardiac disorders1/630/64
Metastatic prostate cancerReproductive system and breast disorders1/630/64
Most frequent other events
Showing 10 of 16
Most frequent other events
EventIntravitreal aflibercept injectionPlacebo
Abdominal painMusculoskeletal and connective tissue disorders1/631/64
Back spasmMusculoskeletal and connective tissue disorders1/630/64
Decreased visual acuity x 6 linesEye disorders1/630/64
Elevated LFTsHepatobiliary disorders1/630/64
Left cavernous sinus lesionMusculoskeletal and connective tissue disorders1/630/64
Lump in right breastReproductive system and breast disorders1/630/64
Meniscus tear, leftMusculoskeletal and connective tissue disorders1/630/64
VomitingGastrointestinal disorders1/630/64
Vulva intraepithelial neoplasia (VIN 3)Skin and subcutaneous tissue disorders1/630/64
HematocheziaGastrointestinal disorders0/631/64

Baseline characteristics

1 patient in Intravitreal aflibercept injection group had exudative disease in the study eye at Baseline, which was exclusionary.

Age, Continuous
Age, Continuous(years)Intravitreal Aflibercept InjectionPlaceboTotal
Mean76.1 ± 7.476.9 ± 8.876.5 ± 8.1
Sex: Female, Male
Sex: Female, Male(Participants)Intravitreal Aflibercept InjectionPlaceboTotal
Female273259
Male363268
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Intravitreal Aflibercept InjectionPlaceboTotal
Count of participants——0
Duration of Fellow Eye nvAMD < 2 Years
Duration of Fellow Eye nvAMD < 2 Years(Participants)Intravitreal Aflibercept InjectionPlaceboTotal
Count of participants303161
Non-exudative Macular NV
Non-exudative Macular NV(Participants)Intravitreal Aflibercept InjectionPlaceboTotal
Count of participants4610
Mean BCVA
Mean BCVA(letters read on ETDRS eye chart)Intravitreal Aflibercept InjectionPlaceboTotal
Mean78.7 ± 8.877.3 ± 10.178.0 ± 9.45
08

Study locations

4 sites
  • Retina-Vitreous Associates Medical Group
    Beverly Hills, California 90211, United States
  • Ophthalmic Consultants of Boston
    Boston, Massachusetts 02114, United States
  • NJ Retina
    Edison, New Jersey 08817, United States
  • Retina Consultants of Houston
    Houston, Texas 77030, United States
09

References and documents

Publications

  • 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. PubMed 33734306 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 23, 2015

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 14, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02462889
Lead sponsor
Jeffrey S Heier
Collaborators
Regeneron Pharmaceuticals
Responsible party
Jeffrey S Heier (Director, Vitreoretinal Service, Ophthalmic Consultants of Boston) — Sponsor-investigator
First posted
Jun 4, 2015
Start date
Jun 2015
Primary completion
Mar 2019
Completion
Mar 2019
Results posted
Nov 14, 2025
Last update
Nov 14, 2025

Study contacts

Jeffrey S Heier, MD
principal investigator · Ophthalmic Consultants of Boston

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.

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