RECOVERY: Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy

Sponsor
Charles C Wykoff, PhD, MD (Other)
Overall Status
Completed
CT.gov ID
NCT02863354
Collaborator
Regeneron Pharmaceuticals (Industry)
43
4
2
33
10.8
0.3

Study Details

Study Description

Brief Summary

The RECOVERY trial will assess the safety and tolerability of 2 mg intravitreal aflibercept injections (IAI) given monthly (Q4WK) or every 12 weeks (Q12WK) for the treatment of retinal capillary non-perfusion (RNP) associated with proliferative diabetic retinopathy (PDR).

  • Assess the safety and tolerability of IAI for the treatment of proliferative diabetic retinopathy by evaluating the incidence and severity of ocular and systemic adverse events through week 52

  • Change in area of retinal capillary non-perfusion, as assessed by central reading center, from baseline through week 52

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The investigational product is intravitreal aflibercept injection, which will be supplied by Regeneron Pharmaceuticals, Inc. in sterile vials for intravitreal (IVT) injection. Vials must be used (defined as entered with needle) only once. All drug supplies are to be kept under recommended storage conditions.

The injection volume will be 50μL (0.05 mL) and will be administered to the subjects by IVT injection.

Study eyes will be assigned randomly (1:1 ratio) to one of the following 2 treatment arms:
  • Group 1- aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Subjects will have a mandatory Year 1 visit at week 48. Subjects have a mandatory visit at week 52 & will not receive treatment. During the second year of follow-up, subjects will be monitored and treated every 12 weeks (Week 60, 72, 84 and 96) with an end of study visit at week 100. If NV or PDR are worse per the pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated monthly through the end of the study.

  • Group 2 - aflibercept 2 mg every 12-weeks for 48 weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through week 48. At week 52 -

  • For subjects without any retinal non-perfusion, monitoring and treatment will continue at every 12 weeks (Week 60, 72, 84, 96) with an end of study visit at week

  • For subjects with visible retinal non-perfusion, monitoring and treatment will be at a 4-week interval (defined as every 28 days + 7 days and at least 21 days between injections). If retinal non-perfusion has completely resolved at week 72, the subject will be switched back to monitoring and treatment every 12 weeks (Week 72, 84, 96).

Pre-specified criteria (subject must meet at least one criterion, which must be documented with imaging):

  1. Increased neovascularization

  2. Decrease in BCVA by 5 or more letters due to progressive DME or PDR

  3. Worsening central subfield diabetic macular edema causing vision loss, with principal investigator or other delegated investigator confirmation

  4. Total area of retinal ischemia increases by 10% as determined by the central reading center

Rescue Treatment At any point throughout the study, for either treatment arm, if PDR progresses despite 3 monthly IAI, a fluorescein angiogram will be performed to evaluate PDR progression. PRP will only be permitted after confirmation of PDR progression with the primary

Study Design

Study Type:
Interventional
Actual Enrollment :
43 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy
Actual Study Start Date :
Aug 1, 2016
Actual Primary Completion Date :
May 1, 2019
Actual Study Completion Date :
May 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Q4WKS

Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study.

Drug: Aflibercept
Intravitreal injection
Other Names:
  • Eylea
  • Experimental: Q12WKS

    Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study.

    Drug: Aflibercept
    Intravitreal injection
    Other Names:
  • Eylea
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [52 and 100 weeks]

      • Assess the safety and tolerability of IAI for the treatment of proliferative diabetic retinopathy by evaluating the incidence and severity of ocular and systemic adverse events through week 52 and week 100.

    Secondary Outcome Measures

    1. Change in Early Treatment of Diabetic Retinopathy Severity Best Corrected Visual Acuity [52 weeks and 100 weeks]

      Mean change in Early Treatment of Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS-BCVA) from baseline to week 52 and week 100.

    2. Change in Area of Retinal Capillary Non-perfusion Within the Macula [52 weeks and 100 weeks]

      Change in area of retinal capillary non-perfusion within the macula compared to baseline, as assessed by ultrawide-field fluorescein angiogram from baseline to week 52 and week 100.

    3. Change in Area of Retinal Capillary Non-perfusion Outside of the Macula [52 weeks and 100 weeks]

      Change in area of retinal capillary non-perfusion outside of the macula from baseline to week 52 and week 100.

    4. Percentage of Subjects With Neovascularization Regression [52 Weeks and 100 Weeks]

      Percentage of subjects with neovascularization regression (reduced area of neovascularization) as measured by the central image reading center from baseline to week 52 and week 100.

    5. Percentage of Subjects With Increased Neovascularization [52 Weeks and 100 Weeks]

      Percentage of subjects with increased neovascularization from baseline to week 52 and week 100.

    6. Percentage of Subjects Who Develop Vitreous Hemorrhage [52 Weeks and 100 Weeks]

      Percentage of subjects who develop vitreous hemorrhage from baseline to week 52 and week 100.

    7. Percentage of Subjects Treated With Pan-retinal Photocoagulation or Vitrectomy [52 Weeks and 100 Weeks]

      Percentage of subjects treated with PRP or vitrectomy for progression of PDR from baseline to week 52 and week 100.

    8. Percentage of Subjects Who Develop Center-involving Diabetic Macular Edema [52 Weeks and 100 Weeks]

      Percentage of subjects, at week 52 and week 100, who develop center-involving diabetic macular edema who did not have center-involving diabetic macular edema at baseline

    9. Changes in Visual Function Outcomes (Self Reported Visual Function) [52 weeks and 100 weeks]

      Changes in self reported visual function utilizing the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) from baseline to week 52 and week 100. The NEI VFQ is a validated measure of patient-reported visual function measured on a scale from 0 (worst function) to 100 (best function).

    10. Mean Change in Central Subfield Thickness [52 weeks and 100 weeks]

      Mean change in central subfield thickness (CST) from baseline to week 52 and week 100

    11. Change in Area of Total Retinal Capillary Non-perfusion, as Assessed by the Central Reading Center [52 weeks and 100 weeks]

      Change in area of total retinal capillary non-perfusion, as assessed by the central reading center, at week 52 and week 100 compared to baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Type 1 or type 2 diabetes mellitus

    2. BCVA ETDRS > 20/400 in the study eye

    3. Willing and able to comply with clinic visits and study-related procedures

    4. Provide signed informed consent

    5. Substantial non perfusion (defined as greater than 20 disc areas), as assessed by the investigator

    6. Early PDR, as assessed by the investigator, with no vitreous hemorrhage*

    • Early PDR is defined in which PRP can safely be deferred and vitreous hemorrhage that does not obscure the application of PRP
    Exclusion Criteria:
    1. Any prior systemic anti-VEGF (anti vascular endothelial growth factor) or IVT anti-VEGF treatment in the study eye,

    2. SD-OCT (Spectral Domain Optical Coherence Tomography) central subfield thickness measurement of > 320 µm, in the study eye

    3. Evidence of infectious ocular infection, in the study eye, at time of screening

    4. History of vitreoretinal surgery in the study eye

    5. Any prior Panretinal laser photocoagulation (PRP) in the study eye

    6. Current vitreous hemorrhage obscuring retinal imaging in the study eye

    7. Cataract surgery in the study eye within 4 weeks of Day 0

    8. Uncontrolled blood pressure (defined as > 180/110 mm Hg systolic/diastolic, while seated)

    9. Significant renal disease defined as a history of chronic renal failure requiring dialysis or renal transplant

    10. Tractional Retinal Detachment threatening the macula in the study eye

    11. Corticosteroid treatment (intravitreal or peribulbar) in the study eye within 12 weeks of screening

    12. Pregnant or breast-feeding women

    13. Sexually active men* or women of childbearing potential who are unwilling to practice adequate contraception during the study. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device (IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly.

    • Contraception is not required for men with documented vasectomy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Retina Consultants of Houston/The Medical Center Houston Texas United States 77030
    2 Retina Consultants of Houston/Katy office Katy Texas United States 77494
    3 Retina Consultants of Houston Kingwood Texas United States 77339
    4 Retina Consultants of Houston The Woodlands Texas United States 77384

    Sponsors and Collaborators

    • Charles C Wykoff, PhD, MD
    • Regeneron Pharmaceuticals

    Investigators

    • Principal Investigator: Charles C Wykoff, PhD, MD, Retina Consultants Houston

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Charles C Wykoff, PhD, MD, Principal Investigator, Greater Houston Retina Research
    ClinicalTrials.gov Identifier:
    NCT02863354
    Other Study ID Numbers:
    • RECOVERY
    First Posted:
    Aug 11, 2016
    Last Update Posted:
    May 24, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Period Title: Year 1
    STARTED 23 20
    COMPLETED 19 18
    NOT COMPLETED 4 2
    Period Title: Year 1
    STARTED 19 18
    COMPLETED 17 16
    NOT COMPLETED 2 2

    Baseline Characteristics

    Arm/Group Title Q4WKS Q12WKS Total
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection Total of all reporting groups
    Overall Participants 23 20 43
    Overall Eyes 20 20 40
    Age (Eyes) [Count of Units]
    <=18 years
    0
    0
    0
    Between 18 and 65 years
    2
    2
    4
    >=65 years
    18
    18
    36
    Age (Years) [Mean (Inter-Quartile Range) ]
    Mean (Inter-Quartile Range) [Years]
    47.7
    48.3
    48
    Sex: Female, Male (Eyes) [Count of Units]
    Female
    11
    8
    19
    Male
    9
    12
    21
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    4.3%
    1
    5%
    2
    4.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    8.7%
    8
    40%
    10
    23.3%
    White
    13
    56.5%
    10
    50%
    23
    53.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    4
    17.4%
    1
    5%
    5
    11.6%
    Region of Enrollment (participants) [Number]
    United States
    20
    87%
    20
    100%
    40
    93%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
    Description • Assess the safety and tolerability of IAI for the treatment of proliferative diabetic retinopathy by evaluating the incidence and severity of ocular and systemic adverse events through week 52 and week 100.
    Time Frame 52 and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    0
    0%
    0
    0%
    Week 100
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Change in Early Treatment of Diabetic Retinopathy Severity Best Corrected Visual Acuity
    Description Mean change in Early Treatment of Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS-BCVA) from baseline to week 52 and week 100.
    Time Frame 52 weeks and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to lost to follow up or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    4.26
    4.53
    Week 100
    4.06
    8.88
    3. Secondary Outcome
    Title Change in Area of Retinal Capillary Non-perfusion Within the Macula
    Description Change in area of retinal capillary non-perfusion within the macula compared to baseline, as assessed by ultrawide-field fluorescein angiogram from baseline to week 52 and week 100.
    Time Frame 52 weeks and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    0.048
    (0.450)
    0.217
    (0.388)
    Week 100
    2.627
    (5.171)
    0.940
    (1.156)
    4. Secondary Outcome
    Title Change in Area of Retinal Capillary Non-perfusion Outside of the Macula
    Description Change in area of retinal capillary non-perfusion outside of the macula from baseline to week 52 and week 100.
    Time Frame 52 weeks and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    182.467
    (202.341)
    240.472
    (121.967)
    Week 100
    342.651
    (135.957)
    387.204
    (169.233)
    5. Secondary Outcome
    Title Percentage of Subjects With Neovascularization Regression
    Description Percentage of subjects with neovascularization regression (reduced area of neovascularization) as measured by the central image reading center from baseline to week 52 and week 100.
    Time Frame 52 Weeks and 100 Weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 18 18
    Week 52
    17
    73.9%
    18
    90%
    Week 100
    17
    73.9%
    15
    75%
    6. Secondary Outcome
    Title Percentage of Subjects With Increased Neovascularization
    Description Percentage of subjects with increased neovascularization from baseline to week 52 and week 100.
    Time Frame 52 Weeks and 100 Weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 18 18
    Week 52
    1
    4.3%
    0
    0%
    Week 100
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Percentage of Subjects Who Develop Vitreous Hemorrhage
    Description Percentage of subjects who develop vitreous hemorrhage from baseline to week 52 and week 100.
    Time Frame 52 Weeks and 100 Weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    2
    8.7%
    1
    5%
    Week 100
    4
    17.4%
    1
    5%
    8. Secondary Outcome
    Title Percentage of Subjects Treated With Pan-retinal Photocoagulation or Vitrectomy
    Description Percentage of subjects treated with PRP or vitrectomy for progression of PDR from baseline to week 52 and week 100.
    Time Frame 52 Weeks and 100 Weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    0
    0%
    0
    0%
    Week 100
    0
    0%
    0
    0%
    9. Secondary Outcome
    Title Percentage of Subjects Who Develop Center-involving Diabetic Macular Edema
    Description Percentage of subjects, at week 52 and week 100, who develop center-involving diabetic macular edema who did not have center-involving diabetic macular edema at baseline
    Time Frame 52 Weeks and 100 Weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    0
    0%
    0
    0%
    Week 100
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title Changes in Visual Function Outcomes (Self Reported Visual Function)
    Description Changes in self reported visual function utilizing the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) from baseline to week 52 and week 100. The NEI VFQ is a validated measure of patient-reported visual function measured on a scale from 0 (worst function) to 100 (best function).
    Time Frame 52 weeks and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    6.27
    (17.54)
    2.23
    (12.86)
    Week 100
    8.91
    (22.04)
    8.82
    (13.33)
    11. Secondary Outcome
    Title Mean Change in Central Subfield Thickness
    Description Mean change in central subfield thickness (CST) from baseline to week 52 and week 100
    Time Frame 52 weeks and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    -32.947
    (20.961)
    -20.813
    (26.684)
    Week 100
    -35.059
    (27.276)
    -23.313
    (31.979)
    12. Secondary Outcome
    Title Change in Area of Total Retinal Capillary Non-perfusion, as Assessed by the Central Reading Center
    Description Change in area of total retinal capillary non-perfusion, as assessed by the central reading center, at week 52 and week 100 compared to baseline.
    Time Frame 52 weeks and 100 weeks

    Outcome Measure Data

    Analysis Population Description
    3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study. Number analyzed at Week 52 and Week 100 differs from overall number analyzed due to inability to analyze images, lost to follow up, or deceased participants.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    Measure Participants 20 20
    Week 52
    -11.994
    (128.697)
    66.752
    (100.546)
    Week 100
    141.317
    (110.523)
    245.694
    (132.051)

    Adverse Events

    Time Frame 52 weeks and 100 weeks
    Adverse Event Reporting Description 3 participants that were enrolled dropped out before their Week 4 visit and were replaced in the study. Thus, only 40 subjects of the original 43 were followed and analyzed in the study.
    Arm/Group Title Q4WKS Q12WKS
    Arm/Group Description Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. Aflibercept: Intravitreal injection Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. Aflibercept: Intravitreal injection
    All Cause Mortality
    Q4WKS Q12WKS
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/20 (0%) 1/20 (5%)
    Serious Adverse Events
    Q4WKS Q12WKS
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/20 (10%) 2/20 (10%)
    Cardiac disorders
    Worsening of Coronary Artery Disease 1/20 (5%) 1 0/20 (0%) 0
    NSTEMI 1/20 (5%) 1 0/20 (0%) 0
    Exacerbation of CHF 1/20 (5%) 1 0/20 (0%) 0
    Endocrine disorders
    Hyperglycemia 1/20 (5%) 1 0/20 (0%) 0
    Infections and infestations
    Acute Osteomyelitis 0/20 (0%) 0 1/20 (5%) 1
    Bacteremia 0/20 (0%) 0 1/20 (5%) 1
    Other (Not Including Serious) Adverse Events
    Q4WKS Q12WKS
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/20 (45%) 8/20 (40%)
    Ear and labyrinth disorders
    Floater 2/20 (10%) 2 1/20 (5%) 1
    Eye disorders
    Worsening Cataract 2/20 (10%) 2 4/20 (20%) 4
    Subconjunctival Hemorrhage 4/20 (20%) 4 0/20 (0%) 0
    Vitreous Hemorrhage 2/20 (10%) 2 1/20 (5%) 1
    Photophobia 2/20 (10%) 2 0/20 (0%) 0
    Eye Pain 1/20 (5%) 1 1/20 (5%) 1
    Eye Irritation 2/20 (10%) 2 0/20 (0%) 0
    Foreign body sensation 1/20 (5%) 1 0/20 (0%) 0
    Ocular Burning 1/20 (5%) 1 0/20 (0%) 0
    Dryness 1/20 (5%) 1 0/20 (0%) 0
    Corneal Haze 0/20 (0%) 0 1/20 (5%) 1
    Acute Follicular Conjunctivitis 0/20 (0%) 0 1/20 (5%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Charles C. Wykoff
    Organization Retina Consultants of Houston
    Phone 713-524-3434
    Email ccwmd@houstonretina.com
    Responsible Party:
    Charles C Wykoff, PhD, MD, Principal Investigator, Greater Houston Retina Research
    ClinicalTrials.gov Identifier:
    NCT02863354
    Other Study ID Numbers:
    • RECOVERY
    First Posted:
    Aug 11, 2016
    Last Update Posted:
    May 24, 2021
    Last Verified:
    May 1, 2021