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Proliferative Diabetic RetinopathyPhase 2RECOVERYNCT02863354

Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy

A Phase 2 study testing Aflibercept in people with Proliferative Diabetic Retinopathy, run by Charles C Wykoff, PhD, MD at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Proliferative Diabetic Retinopathy
What is being tested?
Aflibercept
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
4 sitesUnited States
Study dates
Aug 2016to May 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Type 1 or type 2 diabetes mellitus
  • BCVA ETDRS > 20/400 in the study eye
  • Willing and able to comply with clinic visits and study-related procedures
  • Provide signed informed consent
  • Substantial non perfusion (defined as greater than 20 disc areas), as assessed by the investigator
  • 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

Who cannot join

  • Any prior systemic anti-VEGF (anti vascular endothelial growth factor) or IVT anti-VEGF treatment in the study eye,
  • SD-OCT (Spectral Domain Optical Coherence Tomography) central subfield thickness measurement of > 320 µm, in the study eye
  • Evidence of infectious ocular infection, in the study eye, at time of screening
  • History of vitreoretinal surgery in the study eye
  • Any prior Panretinal laser photocoagulation (PRP) in the study eye
  • Current vitreous hemorrhage obscuring retinal imaging in the study eye
Show all 14Show fewer
  • Cataract surgery in the study eye within 4 weeks of Day 0
  • Uncontrolled blood pressure (defined as > 180/110 mm Hg systolic/diastolic, while seated)
  • Significant renal disease defined as a history of chronic renal failure requiring dialysis or renal transplant
  • Tractional Retinal Detachment threatening the macula in the study eye
  • Corticosteroid treatment (intravitreal or peribulbar) in the study eye within 12 weeks of screening
  • Pregnant or breast-feeding women
  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Retina Consultants of Houston/The Medical Center

    Houston, Texas, 77030

  • Retina Consultants of Houston/Katy office

    Katy, Texas, 77494

  • Retina Consultants of Houston

    Kingwood, Texas, 77339

  • Retina Consultants of Houston

    The Woodlands, Texas, 77384

Other trials in United States

About this study

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
Read the 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

Being tested
Aflibercept

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfliberceptDrug

    Also called Eylea

    Intravitreal injection

Study groups in NCT02863354
Study groupRoleWhat they receive
Q4WKSExperimentalAflibercept 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.
Receives: Drug: Aflibercept
Q12WKSExperimentalAflibercept 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.
Receives: Drug: Aflibercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    • 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.

    Measured: 52 and 100 weeks

Secondary outcomes (11)

  1. Change in Early Treatment of Diabetic Retinopathy Severity Best Corrected Visual Acuity

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

    Measured: 52 weeks and 100 weeks

  2. Change in Area of Retinal Capillary Non-perfusion Within the Macula

    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.

    Measured: 52 weeks and 100 weeks

  3. Change in Area of Retinal Capillary Non-perfusion Outside of the Macula

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

    Measured: 52 weeks and 100 weeks

  4. Percentage of Subjects With Neovascularization Regression

    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.

    Measured: 52 Weeks and 100 Weeks

  5. Percentage of Subjects With Increased Neovascularization

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

    Measured: 52 Weeks and 100 Weeks

  6. Percentage of Subjects Who Develop Vitreous Hemorrhage

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

    Measured: 52 Weeks and 100 Weeks

  7. Percentage of Subjects Treated With Pan-retinal Photocoagulation or Vitrectomy

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

    Measured: 52 Weeks and 100 Weeks

  8. Percentage of Subjects Who Develop Center-involving Diabetic Macular Edema

    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

    Measured: 52 Weeks and 100 Weeks

  9. Changes in Visual Function Outcomes (Self Reported Visual Function)

    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).

    Measured: 52 weeks and 100 weeks

  10. Mean Change in Central Subfield Thickness

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

    Measured: 52 weeks and 100 weeks

  11. Change in Area of Total Retinal Capillary Non-perfusion, as Assessed by the Central Reading Center

    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.

    Measured: 52 weeks and 100 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionMay 2019
  4. Study completionMay 2019

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02863354
Sponsor's protocol ID
RECOVERY
Acronym
RECOVERY
Status last verified
May 2021
First submitted
4 Aug 2016
Last updated
24 May 2021
Data monitoring committee
No
Individual data sharing
No

Publications

  • Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63. doi: 10.1001/archopht.122.4.552.

    PubMed 15078674

  • Klein R, Klein BE, Moss SE. A population-based study of diabetic retinopathy in insulin-using patients diagnosed before 30 years of age. Diabetes Care. 1985 Sep-Oct;8 Suppl 1:71-6. doi: 10.2337/diacare.8.1.s71.

    PubMed 4053957

  • Preliminary report on effects of photocoagulation therapy. The Diabetic Retinopathy Study Research Group. Am J Ophthalmol. 1976 Apr;81(4):383-96. doi: 10.1016/0002-9394(76)90292-0.

    PubMed 944535

  • Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.

    PubMed 26565927

  • Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981 Jul;88(7):583-600.

    PubMed 7196564

  • Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766-85.

    PubMed 2062512

  • Ferris F. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc. 1996;94:505-37.

    PubMed 8981711

  • Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. doi: 10.1056/NEJM199412013312203.

    PubMed 7526212

  • Ip MS, Domalpally A, Hopkins JJ, Wong P, Ehrlich JS. Long-term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol. 2012 Sep;130(9):1145-52. doi: 10.1001/archophthalmol.2012.1043.

    PubMed 22965590

  • Ip MS, Domalpally A, Sun JK, Ehrlich JS. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology. 2015 Feb;122(2):367-74. doi: 10.1016/j.ophtha.2014.08.048. Epub 2014 Nov 18.

    PubMed 25439595

  • Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, Heier JS, Terasaki H, Kaiser PK, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Korobelnik JF. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015 Oct;122(10):2044-52. doi: 10.1016/j.ophtha.2015.06.017. Epub 2015 Jul 18.

    PubMed 26198808

  • Campochiaro PA, Wykoff CC, Singer M, Johnson R, Marcus D, Yau L, Sternberg G. Monthly versus as-needed ranibizumab injections in patients with retinal vein occlusion: the SHORE study. Ophthalmology. 2014 Dec;121(12):2432-42. doi: 10.1016/j.ophtha.2014.06.011. Epub 2014 Jul 21.

    PubMed 25060610

  • 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.

  • Babiuch A, Wykoff CC, Hach J, Srivastava S, Talcott KE, Yu HJ, Nittala M, Sadda S, Ip MS, Le T, Hu M, Reese J, Ehlers JP. Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study. Br J Ophthalmol. 2021 Aug;105(8):1111-1115. doi: 10.1136/bjophthalmol-2020-316952. Epub 2020 Aug 22.

    PubMed 32829304

  • Alagorie AR, Nittala MG, Velaga S, Zhou B, Rusakevich AM, Wykoff CC, Sadda SR. Association of Intravitreal Aflibercept With Optical Coherence Tomography Angiography Vessel Density in Patients With Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Aug 1;138(8):851-857. doi: 10.1001/jamaophthalmol.2020.2130.

    PubMed 32584384

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aflibercept in people with Proliferative Diabetic Retinopathy, run by Charles C Wykoff, PhD, MD 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 7 inclusion and 14 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 24 May 2021. 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. 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 21 Apr 2021). 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?

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (time frame: 52 and 100 weeks). 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 NCT02863354, which also lists 16 linked publications.

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 24 May 2021.

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