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Trial record 4 of 6 for:    15078674 [PUBMED-IDS]

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

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ClinicalTrials.gov Identifier: NCT02863354
Recruitment Status : Active, not recruiting
First Posted : August 11, 2016
Last Update Posted : December 21, 2017
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Charles C Wykoff, PhD, MD, Greater Houston Retina Research

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
Proliferative Diabetic Retinopathy Drug: Aflibercept 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 100.
    • 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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 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 : August 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


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.
Drug: Aflibercept
Intravitreal injection
Other Name: 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. 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.
Drug: Aflibercept
Intravitreal injection
Other Name: Eylea




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 52 and 104 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


Secondary Outcome Measures :
  1. Change in Early Treatment of Diabetic Retinopathy Severity Best Corrected Visual Acuity [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Mean change in Early Treatment of Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS-BCVA) from baseline to week 52

  2. Change in area of retinal capillary non-perfusion within the macula [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Change in area of retinal capillary non-perfusion within the macula, as assessed by ultrawide-field fluorescein angiogram from baseline to week 52

  3. Change in area of retinal capillary non-perfusion outside of the macula [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Change in area of retinal capillary non-perfusion outside of the macula from baseline to week 52

  4. Percentage of subjects with neovascularization regression [ Time Frame: 52 Weeks and 104 Weeks ]
    Percentage of subjects with neovascularization regression from baseline to week 52

  5. Percentage of subjects with increased neovascularization [ Time Frame: 52 Weeks and 104 Weeks ]
    Percentage of subjects with increased neovascularization from baseline to week 52

  6. Percentage of subjects who develop vitreous hemorrhage [ Time Frame: 52 Weeks and 104 Weeks ]
    Percentage of subjects who develop vitreous hemorrhage from baseline to week 52

  7. Percentage of subjects treated with pan-retinal photocoagulation or vitrectomy [ Time Frame: 52 Weeks and 104 Weeks ]
    Percentage of subjects treated with PRP or vitrectomy for progression of PDR from baseline to week 52

  8. Percentage of subjects who develop center-involving diabetic macular edema [ Time Frame: 52 Weeks and 104 Weeks ]
    Percentage of subjects, at week 52, who develop center-involving diabetic macular edema who did not have center-involving diabetic macular edema at baseline

  9. Changes in visual function outcomes (Humphrey visual field) [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Mean change in peripheral visual field as measured by Humphrey visual field from screen and week 52.

  10. Changes in visual function outcomes (self reported visual function) [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Changes in self reported visual function utilizing the NEI VFQ25 from baseline to week 52

  11. Mean change in central retinal thickness [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Mean change in central retinal thickness (CRT) from baseline to week 52

  12. Change in area of retinal capillary non-perfusion [ Time Frame: Baseline, 52 weeks, and 104 weeks ]
    Change in area of retinal capillary non-perfusion, as assessed by central reading center, from baseline to week 52



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02863354


Locations
United States, Texas
Retina Consultants of Houston/The Medical Center
Houston, Texas, United States, 77030
Retina Consultants of Houston/Katy office
Katy, Texas, United States, 77494
Retina Consultants of Houston
Kingwood, Texas, United States, 77339
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

Publications:
Heier J. The Effect of Intravitreal Aflibercept on Capillary Non-perfusion in Patients with Proliferative Retinopathy and/or Macular Edema Secondary to Proliferative Diabetic Retinopathy and Central Retinal Venous Occlusive Disease (ANDROID Study). Retina Society, Paris, France. 2015.

Responsible Party: Charles C Wykoff, PhD, MD, Principal Investigator, Greater Houston Retina Research
ClinicalTrials.gov Identifier: NCT02863354     History of Changes
Other Study ID Numbers: RECOVERY
First Posted: August 11, 2016    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases