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

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ClinicalTrials.gov Identifier: NCT03531294
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : July 3, 2018
Sponsor:
Collaborators:
Regeneron Pharmaceuticals
The Cleveland Clinic
Information provided by (Responsible Party):
Greater Houston Retina Research

Brief Summary:

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- 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 (this equates to less than a 2 step DRSS improvement compared to baseline DRSS). If such worsening is detected, the subject would resume monthly IAI until a greater than or equal to 2 step DRSS improvement compared to baseline 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.

Group 2 - 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 wide field (WF) fluorescein angiography (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.

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.


Condition or disease Intervention/treatment Phase
Diabetic Retinopathy Drug: Aflibercept Injection Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement
Actual Study Start Date : May 23, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1
Treatment based on central reading center reading evaluation of DRSS (diabetic retinopathy severity scale) level based on OPTOS funds photos.
Drug: Aflibercept Injection
intravitreal 2mg aflibercept injection
Other Name: Eyela

Experimental: Group 2
Treatment based on central reading center reading evaluation of DRSS (diabetic retinopathy severity scale) level based leakage index of OPTOS wide field fluorescein angiography.
Drug: Aflibercept Injection
intravitreal 2mg aflibercept injection
Other Name: Eyela




Primary Outcome Measures :
  1. Incidence of Adverse Events for diabetic retinopathy subjects who receive intravitreal Aflibercept [ Time Frame: 52 weeks ]
    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


Secondary Outcome Measures :
  1. Correlation of DRSS and leakage index [ Time Frame: 52 weeks ]
    Correlation of reading-center determined DRSS level and leakage index to determine change in DR severity

  2. Correlation between Reading Center DRSS Level and Physician determined DR severity [ Time Frame: 52 weeks ]
    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)

  3. Number of IAI [ Time Frame: 52 weeks ]
    Mean and Median number of IVT aflibercept Injections (with and without IAI given for DME)

  4. Mean number of IAI (NPDR VS PDR) [ Time Frame: 52 weeks ]
    Mean number of IVT aflibercept Injections in eyes with baseline NPDR vs PDR through week 52

  5. ETDRS-BCVA change [ Time Frame: 52 weeks ]
    Mean change in Early Treatment Diabetic Retinopathy Study best corrected visual acuity (ETDRS-BCVA)

  6. Changes in Visual Function [ Time Frame: 52 weeks ]
    Changes in visual function outcomes as measured by National Eye Institute Visual Functioning Questionnaire (NEI-VFQ)

  7. DRSS Change [ Time Frame: 52 weeks ]
    Changes in DRSS

  8. Change in Non-Perfusion [ Time Frame: 52 weeks ]
    Change in area of retinal non-perfusion within the macula and periphery

  9. Change in Vascular Leakage [ Time Frame: 52 weeks ]
    Change in relative area of vascular leakage on wide-field fluorescein angiography

  10. Change in microaneurysms [ Time Frame: 52 weeks ]
    Change in number of microaneurysms, assessed by wide-field fluorescein angiography

  11. Change in CST [ Time Frame: 52 weeks ]
    Mean change in central subfield thickness (CST), as assessed by spectral Domain Optical coherence tomography (SD-OCT)

  12. DME development [ Time Frame: 52 weeks ]
    Percentage of subjects, who develop center-involving diabetic macular edema necessitating treatment compared to baseline

  13. PDR Development [ Time Frame: 52 weeks ]
    Percentage of subjects, who develop a new PDR event compared to baseline

  14. Cytokine Levels [ Time Frame: 52 weeks ]
    Corelation of cytokine levels in aqueous humor samples to clinical and imaging outcomes



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

Exclusion Criteria:

  1. 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
  2. Any intravitreal or peribulbar corticosteroids in the study eye within 12 weeks of screening/baseline
  3. Any prior treatment with Ozurdex or Iluvien in the study eye
  4. SD-OCT central subfield thickness (CST) > 320 µm in the study eye
  5. Central DME causing visual acuity loss, in which treatment can not be safely deferred for at least 6 months, in the investigator's judgment
  6. Current visually significant vitreous hemorrhage in the study eye. Vitreous hemorrhage is allowed as long as DRSS level is 71A or lower.
  7. History of panretinal photocoagulation (PRP) in the study eye
  8. History of vitrectomy surgery in the study eye
  9. Cataract surgery in the study eye within 8 weeks of screening/baseline
  10. Pregnant or breast-feeding women
  11. 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.

  12. If currently receiving diaylisis, must have started treatment more than 12 weeks prior to screening/baseline
  13. Uncontrolled blood pressure (defined as > 190/110 mm Hg systolic/diastolic, while seated)

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): NCT03531294


Contacts
Contact: Cassie Cone, BA 713-394-7537 cassandra.cone@houstonretina.com
Contact: Melisa Bocanegra 713-524-3434 melisa.bocanegra@houstonretina.com

Locations
United States, Texas
Retina Consultants of Houston/The Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Cassie Cone, BA    713-524-3434    ccone@houstonretina.com   
Sub-Investigator: David M Brown, MD         
Sub-Investigator: Matthew S Benz, MD         
Sub-Investigator: James C Major, MD         
Sub-Investigator: Tien P Wong, MD         
Sub-Investigator: Amy C Schefler, MD         
Sub-Investigator: Richard H Fish, MD         
Sub-Investigator: Rosa Y Kim, MD         
Sub-Investigator: Eric Chen, MD         
Principal Investigator: Charles C Wyoff, PhD, MD         
Sub-Investigator: Ankoor R Shah, MD         
Sub-Investigator: Christopher R Henry, MD         
Retina Consultants of Houston Recruiting
The Woodlands, Texas, United States, 77384
Contact: Melisa Bocanegra    713-524-3434    melisa.bocanegra@houstonretina.com   
Sub-Investigator: David M Brown, MD         
Principal Investigator: Charles C Wykoff, MD         
Sub-Investigator: Matthew S Benz, MD         
Sub-Investigator: Eric Chen, MD         
Sub-Investigator: Richard H Fish, MD         
Sub-Investigator: James C Major, MD         
Sub-Investigator: Amy C Schefler, MD         
Sub-Investigator: Tien P Wong, MD         
Sub-Investigator: Ankoor R Shah, MD         
Sub-Investigator: Christopher R Henry, MD         
Sponsors and Collaborators
Greater Houston Retina Research
Regeneron Pharmaceuticals
The Cleveland Clinic

Additional Information:
Publications:
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

Responsible Party: Greater Houston Retina Research
ClinicalTrials.gov Identifier: NCT03531294     History of Changes
Other Study ID Numbers: PRIME
First Posted: May 21, 2018    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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