Age-Related Macular DegenerationPhase 2PRO-CONNCT02462889
IAI Versus Sham as Prophylaxis Against Conversion to Neovascular AMD
A Phase 2 study testing Intravitreal aflibercept injection in people with Age-Related Macular Degeneration, run by Jeffrey S Heier at 4 sites in United States.
Trial 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 more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Age-Related Macular Degeneration
- What is being tested?
- Intravitreal aflibercept injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2015to Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Retina-Vitreous Associates Medical Group
Beverly Hills, California, 90211
Ophthalmic Consultants of Boston
Boston, Massachusetts, 02114
NJ Retina
Edison, New Jersey, 08817
Retina Consultants of Houston
Houston, Texas, 77030
About this study
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
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.
- Conditions
- Age-Related Macular Degeneration
- Being tested
- Intravitreal aflibercept injection, Placebo
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal aflibercept injectionDrug
Also called Eylea
Intravitreal aflibercept injection
PlaceboDrug
Also called Sham injection
Sham injection
| Study group | Role | What they receive |
|---|---|---|
| Intravitreal aflibercept injection | Experimental | Subjects will be randomized to receive intravitreal aflibercept injection every three months for 24 months. Receives: Drug: Intravitreal aflibercept injection |
| Placebo | Placebo comparator | Subjects will be randomized to receive sham injection every three months for 24 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (4)
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.
Measured: up to Month 24
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.
Measured: up to Month 24
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.
Measured: 24 months
Mean Change in Growth of Geographic Atrophy.
Mean change in growth of geographic atrophy from baseline to Month 24.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Age-Related Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey S Heier
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor-investigator, Jeffrey S Heier, Ophthalmic Consultants of Boston
- Investigators
- Jeffrey S Heier, MD, Principal investigator, Ophthalmic Consultants of Boston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02462889
- Sponsor's protocol ID
- VGFTe-AMD-1507
- Acronym
- PRO-CON
- Status last verified
- Oct 2025
- First submitted
- 2 Jun 2015
- Last updated
- 14 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 14 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02462889
- Acronym / sponsor ID
- PRO-CON / VGFTe-AMD-1507
- Conditions
- Age-Related Macular Degeneration
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Jeffrey S HeierUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Jun 2015 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Posted 14 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravitreal aflibercept injection | Experimental | Drug: Intravitreal aflibercept injectionSubjects will be randomized to receive intravitreal aflibercept injection every three months for 24 months. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized to receive sham injection every three months for 24 months. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravitreal aflibercept injectionAlso: EyleaIntravitreal aflibercept injection | Drug | Intravitreal aflibercept injection |
| PlaceboAlso: Sham injectionSham injection | Drug | Placebo |
Primary outcome
Percentage of Subjects Converting to Exudative AMD at 24 Months.
Time frame: 24 months
Percentage of subjects converting to exudative AMD at 24 months as confirmed by independent masked reading center.
4 secondary outcomes
Percentage of Patients Converted to Exudative AMD Who Had Exudative AMD in Fellow Eye ≤ 2 Years at Baseline.
Time frame: up to Month 24
Percentage of Patient Converted to Exudative AMD Based on Presence of Nonexudative CNV.
Time frame: up to Month 24
Mean Change in Best-corrected Visual Acuity at 24 Months Compared to Baseline
Time frame: 24 months
Mean Change in Growth of Geographic Atrophy.
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33734306Heier 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey S Heier, MD principal investigator
Ophthalmic Consultants of Boston
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravitreal aflibercept injection in people with Age-Related Macular Degeneration, run by Jeffrey S Heier at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects Converting to Exudative AMD at 24 Months. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02462889, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2025.