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

Diabetic Retinopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03531294
• Other study ID #: PRIME
• Status: Completed
• Phase: Phase 2
• Start date: May 23, 2018
• Est. completion date: April 9, 2021

Study information

• Verified date: May 2021
• Source: Greater Houston Retina Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 leakage index on OPTOS WF-FA.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 9, 2021
• Est. primary completion date: April 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• Aflibercept Injection
intravitreal 2mg aflibercept injection

Locations

Country	Name	City	State
United States	Retina Consultants of Houston/The Medical Center	Houston	Texas
United States	Retina Consultants of Houston	The Woodlands	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Greater Houston Retina Research	Regeneron Pharmaceuticals, The Cleveland Clinic

Country where clinical trial is conducted

United States, 

References & Publications (30)

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	104 weeks
Secondary	Correlation of DRSS and leakage index	Correlation of reading-center determined DRSS level and leakage index to determine change in DR severity	104 weeks
Secondary	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)	104 weeks
Secondary	Number of IAI	Mean and Median number of IVT aflibercept Injections (with and without IAI given for DME)	104 weeks
Secondary	Mean number of IAI (NPDR VS PDR)	Mean number of IVT aflibercept Injections in eyes with baseline NPDR vs PDR through week 52	104 weeks
Secondary	ETDRS-BCVA change	Mean change in Early Treatment Diabetic Retinopathy Study best corrected visual acuity (ETDRS-BCVA)	104 weeks
Secondary	Changes in Visual Function	Changes in visual function outcomes as measured by National Eye Institute Visual Functioning Questionnaire (NEI-VFQ)	104 weeks
Secondary	DRSS Change	Changes in DRSS	104 weeks
Secondary	Change in Non-Perfusion	Change in area of retinal non-perfusion within the macula and periphery	104 weeks
Secondary	Change in Vascular Leakage	Change in relative area of vascular leakage on wide-field fluorescein angiography	104 weeks
Secondary	Change in microaneurysms	Change in number of microaneurysms, assessed by wide-field fluorescein angiography	104 weeks
Secondary	Change in CST	Mean change in central subfield thickness (CST), as assessed by spectral Domain Optical coherence tomography (SD-OCT)	104 weeks
Secondary	DME development	Percentage of subjects, who develop center-involving diabetic macular edema necessitating treatment compared to baseline	104 weeks
Secondary	PDR Development	Percentage of subjects, who develop a new PDR event compared to baseline	104 weeks
Secondary	Cytokine Levels	Corelation of cytokine levels in aqueous humor samples to clinical and imaging outcomes	104 weeks

External Links

•   2016 America Society of Retina Specialists Preferences and Trends Survey
•   World Helath Organization (WHO). Global Report on Diabetes. 2016