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Diabetic RetinopathyPhase 2NCT03531294

Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement

A Phase 2 study testing Aflibercept Injection in people with Diabetic Retinopathy, run by Greater Houston Retina Research at 2 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

The PRIME trial will assess the safety of 2 mg intravitreal aflibercept injections (IAI) to achieve and maintain DRSS improvements (2 or more steps) in patients with a baseline DRSS level of 47A to 71A inclusive through 104 weeks as determined by reading center determined DRSS gradings on OPTOS fundus photos and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetic Retinopathy
What is being tested?
Aflibercept Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
23 May 2018to 9 Apr 2021
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Men or Women > 18 years of age with type 1 or II diabetes mellitus
  • Diabetic Retinopathy, DRSS Level 47A to 71A, as assessed by CRC (enrollment of PDR levels will be limited to 50% of the total population)
  • BCVA in the study eye better than 20/800

Who cannot join

  • Any prior systemic anti-VEGF treatment or IVT anti-search vascular endothelial growth factor (VEGF) treatment in the study eye within 24 weeks of screening/baseline
  • Any intravitreal or peribulbar corticosteroids in the study eye within 12 weeks of screening/baseline
  • Any prior treatment with Ozurdex or Iluvien in the study eye
  • SD-OCT central subfield thickness (CST) > 320 µm in the study eye
  • Central DME causing visual acuity loss, in which treatment can not be safely deferred for at least 6 months, in the investigator's judgment
  • Current visually significant vitreous hemorrhage in the study eye. Vitreous hemorrhage is allowed as long as DRSS level is 71A or lower.
Show all 15Show fewer
  • History of panretinal photocoagulation (PRP) in the study eye
  • History of vitrectomy surgery in the study eye
  • Cataract surgery in the study eye within 8 weeks of screening/baseline
  • Pregnant or breast-feeding women
  • Sexually active men* or women of childbearing potential** who are unwilling to practiceadequate 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/baseline; 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.
  • Postmenopausal women must be amenorrheic for at least 52 weeks in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
  • If currently receiving diaylisis, must have started treatment more than 12 weeks prior to screening/baseline
  • Uncontrolled blood pressure (defined as > 190/110 mm Hg systolic/diastolic, while seated)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Retina Consultants of Houston/The Medical Center

    Houston, Texas, 77030

  • Retina Consultants of Houston

    The Woodlands, Texas, 77384

Other trials in United States

About this study

The PRIME trial will assess the safety of 2 mg intravitreal aflibercept injections (IAI) to achieve and maintain DRSS improvements (2 or more steps) in patients with a baseline DRSS level of 47A to 71A inclusive through 104 weeks as determined by reading center determined DRSS gradings on OPTOS fundus photos and leakage index on OPTOS WF-FA.

Read the detailed description

Study eyes will be assigned randomly (1:1 ratio) to one of the following 2 treatment arms. Randomization of PDR subjects will be limited to 50% of each arm.

Group 1

Year 1 Subjects will be seen every month, 28 days (+ 7 days), for 52 weeks. All subjects will receive IAI at baseline, after eligibility is confirmed. Week 4 through week 48, subjects will be seen monthly and treated with IAI PRN (pro re nata) according to, same day, central reading center (CRC) determined DRSS level. Monthly treatment with IAI will continue until a greater than or equal to 2 step DRSS level improvement is achieved, relative to screening/baseline DRSS based on CRC assessment OPTOS fundus photos (FP). Subjects who have baseline proliferative diabetic retinopathy (PDR) (DRSS Level 61-71) will continue to receive monthly IAI until a greater than or equal to 2 step DRSS improvement is achieved as determined by CRC assessment of OPTOS fundus photos relative to screening/baseline DRSS, and PDR is quiescent according to the treating investigator. Treatment with IAI will be reinitiated if a 1 step worsening of DRSS occurs compared to best DRSS score achieved, determined by CRC evaluation of OPTOS fundus photos. If such worsening is detected, the subject would resume monthly IAI until best DRSS score or greater is achieved, as determined by CRC assessment of OPTOS fundus photos. In addition, retreatment will also be re-started if new onset neovascularization is identified and is continued until the PDR is quiescent according to the treating investigator.

Year 2 Beginning in year 2 (week 52) subjects will be seen every 56 days (+ 14 days) and treated with IAI PRN (pro re nata) utilizing the same criteria from year 1. All subjects will have a mandatory week 104 visit, where treatment will not be given.

Group 2

Year 1 Subjects will be seen every month, 28 days (+ 7 days), for 52 weeks. All subjects will receive IAI at baseline, after eligibility is confirmed. Week 4 through week 48, subjects will be seen monthly and treated with IAI PRN (pro re nata) according to, same day, CRC determination of DRSS initially, and subsequently of leakage index.

Monthly treatment with IAI will continue until a greater than or equal to 2 step DRSS level improvement is achieved, relative to screening/baseline DRSS based on CRC assessment OPTOS fundus photos (FP). Subjects who have baseline proliferative diabetic retinopathy (PDR) (DRSS Level 61-71) will continue to receive monthly IAI until a greater than or equal to 2 step DRSS improvement is achieved as determined by CRC assessment of OPTOS fundus photos relative to screening/baseline DRSS, and PDR is quiescent according to the treating investigator.

Leakage index as determined by CRC assessment of OPTOS WF-FA at the visit at which a greater than or equal to 2 step DRSS level improvement is achieved will be considered the threshold. Treatment with IAI will be reinitiated if the leakage index increases to 33% above the individual subject threshold leakage index level as determined by CRC evaluation of OPTOS WF-FA. If such worsening is detected, the subject would resume monthly IAI until the threshold leakage index as determined by CRC assessment of OPTOS WF-FA is reached. In addition, retreatment will also be re-started if new onset neovascularization is identified and is continued until the PDR is quiescent according to the treating investigator.

Year 2 Beginning in year 2 (week 52) subjects will be seen every 56 days (+ 14 days) and treated with IAI PRN (pro re nata) utilizing the same criteria from year 1. All subjects will have a mandatory week 104 visit, where treatment will not be given.

If images of insufficient quality are unable to be obtained, in Group 1 or Group 2, subjects will undergo treatment with IAI at principal investigators discretion or designee.

Subjects can have both eyes in the study, if eligibility is met. If both eyes are eligible, one eye will be randomized to group 1 while the other is randomized to group 2. If only one eye is eligible IAI will be provided for the fellow eye as needed according to the treating investigator.

Being tested
Aflibercept Injection
Medical subject headings
Diabetic Retinopathy

What participants receive

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

  • Aflibercept InjectionDrug

    Also called Eyela

    intravitreal 2mg aflibercept injection

Study groups in NCT03531294
Study groupRoleWhat they receive
Group 1ExperimentalTreatment based on central reading center reading evaluation of DRSS (diabetic retinopathy severity scale) level based on OPTOS funds photos.
Receives: Drug: Aflibercept Injection
Group 2ExperimentalTreatment based on central reading center reading evaluation of DRSS (diabetic retinopathy severity scale) level based leakage index of OPTOS wide field fluorescein angiography.
Receives: Drug: Aflibercept Injection

What is being measured

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

  1. Incidence of Adverse Events for diabetic retinopathy subjects who receive intravitreal Aflibercept

    Assess the safety of 2 mg intravitreal aflibercept injections (IAI) to achieve and maintain DRSS improvements (2 or more steps) in patients with a baseline DRSS level of 47A to 71A inclusive as determined by reading center determined DRSS gradings on OPTOS fundus photos and leakage index on OPTOS WF-FA

    Measured: 104 weeks

Secondary outcomes (14)

  1. Correlation of DRSS and leakage index

    Correlation of reading-center determined DRSS level and leakage index to determine change in DR severity

    Measured: 104 weeks

  2. Correlation between Reading Center DRSS Level and Physician determined DR severity

    Correlation of reading-center determined DRSS level and investigator-determined DR severity level based on ophthalmoscopic fundus examination (Physician determined DR severity level will be based on AAO (American Academy of Ophthalmology) simplified grading system: mild NPDR, moderate NPDR, Severe NPDR, low risk PDR, high risk PDR)

    Measured: 104 weeks

  3. Number of IAI

    Mean and Median number of IVT aflibercept Injections (with and without IAI given for DME)

    Measured: 104 weeks

  4. Mean number of IAI (NPDR VS PDR)

    Mean number of IVT aflibercept Injections in eyes with baseline NPDR vs PDR through week 52

    Measured: 104 weeks

  5. ETDRS-BCVA change

    Mean change in Early Treatment Diabetic Retinopathy Study best corrected visual acuity (ETDRS-BCVA)

    Measured: 104 weeks

  6. Changes in Visual Function

    Changes in visual function outcomes as measured by National Eye Institute Visual Functioning Questionnaire (NEI-VFQ)

    Measured: 104 weeks

  7. DRSS Change

    Changes in DRSS

    Measured: 104 weeks

  8. Change in Non-Perfusion

    Change in area of retinal non-perfusion within the macula and periphery

    Measured: 104 weeks

  9. Change in Vascular Leakage

    Change in relative area of vascular leakage on wide-field fluorescein angiography

    Measured: 104 weeks

  10. Change in microaneurysms

    Change in number of microaneurysms, assessed by wide-field fluorescein angiography

    Measured: 104 weeks

  11. Change in CST

    Mean change in central subfield thickness (CST), as assessed by spectral Domain Optical coherence tomography (SD-OCT)

    Measured: 104 weeks

  12. DME development

    Percentage of subjects, who develop center-involving diabetic macular edema necessitating treatment compared to baseline

    Measured: 104 weeks

  13. PDR Development

    Percentage of subjects, who develop a new PDR event compared to baseline

    Measured: 104 weeks

  14. Cytokine Levels

    Corelation of cytokine levels in aqueous humor samples to clinical and imaging outcomes

    Measured: 104 weeks

Timeline

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

  1. First posted21 May 2018
  2. Study start23 May 2018
  3. Primary completion9 Apr 2021
  4. Study completion9 Apr 2021

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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03531294
Sponsor's protocol ID
PRIME
Status last verified
May 2021
First submitted
25 Apr 2018
Last updated
21 May 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ehlers JP, Wang K, Vasanji A, Hu M, Srivastava SK. Automated quantitative characterisation of retinal vascular leakage and microaneurysms in ultra-widefield fluorescein angiography. Br J Ophthalmol. 2017 Jun;101(6):696-699. doi: 10.1136/bjophthalmol-2016-310047. Epub 2017 Apr 21.

    PubMed 28432113

  • Wang K, Srivastava SK, Vasanji A, Hu M, Reese J, Stiegel L, and Ehlers JP. "Quantitative ultrawidefield fluorescein angiography and volumetric optical coherence tomography analysis in the REACT Study: A prospective randomized comparative dosage trial evaluating ranibizumab in bevacizumab-resistant diabetic macular edema." Scientific Poster. ARVO Annual Meeting. Baltimore, MD. May 2017.

  • Ehlers JP. "Peripheral and Macular Retinal Vascular Dynamics in DME and RVO Following Aflibercept Therapy: The PERMEATE Study 6-month Results" Scientific presentation. ASRS Annual Meeting. Boston, MA. August 201

  • 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

  • Leasher JL, Bourne RR, Flaxman SR, Jonas JB, Keeffe J, Naidoo K, Pesudovs K, Price H, White RA, Wong TY, Resnikoff S, Taylor HR; Vision Loss Expert Group of the Global Burden of Disease Study. Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990 to 2010. Diabetes Care. 2016 Sep;39(9):1643-9. doi: 10.2337/dc15-2171.

    PubMed 27555623

  • Bourne RR, Stevens GA, White RA, Smith JL, Flaxman SR, Price H, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, Resnikoff S, Taylor HR; Vision Loss Expert Group. Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health. 2013 Dec;1(6):e339-49. doi: 10.1016/S2214-109X(13)70113-X. Epub 2013 Nov 11.

    PubMed 25104599

  • 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

  • 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

  • Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

    PubMed 20427088

  • Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.

    PubMed 22330964

  • Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, 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, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.

    PubMed 25012934

  • Fong DS, Girach A, Boney A. Visual side effects of successful scatter laser photocoagulation surgery for proliferative diabetic retinopathy: a literature review. Retina. 2007 Sep;27(7):816-24. doi: 10.1097/IAE.0b013e318042d32c.

    PubMed 17891003

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

    PubMed 8981711

  • 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

  • Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.

    PubMed 25692915

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aflibercept Injection in people with Diabetic Retinopathy, run by Greater Houston Retina Research at 2 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 3 inclusion and 15 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 21 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 2 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of Adverse Events for diabetic retinopathy subjects who receive intravitreal Aflibercept (time frame: 104 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 NCT03531294, which also lists 31 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 21 May 2021.

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