Clinical trial NCT03340610: IAI for Persistent DME After Treatment With Bevacizumab And Ranibizumab
Official title: Intravitreal Alflibercept Injection (IAI) for Persistent Diabetic Macular Edema (DME) After Treatment With Bevacizumab And Ranibizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Macular Edema
Lead sponsor: Southeast Retina Center, Georgia
Sponsor class: OTHER
First posted: 2017-11-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 4 prospective, nonrandomized, open label, interventional clinical trial. Study eyes will receive 5 required initial monthly Intravitreal Aflibercept (IAI) doses of 2 mg followed by 2q8 IAI for a total of 52 weeks; only one study eye from each patient will be enrolled.

Detailed description: This is a phase 4 prospective, nonrandomized, open label, interventional clinical trial. Study eyes will receive 5 required initial monthly IAI doses of 2 mg followed by 2q8 IAI for a total of 52 weeks; only one study eye from each patient will be enrolled.

Starting at week 24, patients may be eligible to receive additional 2mg IAI (2q4) treatment if both of the following criteria is met and the investigator feels additional treatment would be beneficial:

* Loss of \>5 letters from baseline or best previously recorded best corrected visual acuity (BCVA)
* Presence of new or recurrent intraretinal fluid or subretinal fluid as assessed by SD OCT

Starting at week 24, rescue therapy with macular laser photocoagulation may be administered if any the following criteria are met

* Loss of \> 15 letters from baseline or best previously recorded BCVA and loss of acuity felt to be secondary to Diabetic Macular Edema (DME) and not from other cause (i.e., cataract, epiretinal membrane, vitreous hemorrhage, etc) and investigator feels patient would benefit from rescue therapy
* Increase in SD OCT CSF \> 100 um from baseline or best previously recorded SD OCT CSF and investigator feels patient would benefit from rescue therapy.

Every 4 week visit will include ETDRS BCVA, IOP measurement, Slit lamp biomicroscopy, Indirect ophthalmoscopy, Heidelberg Spectralis SD-OCT and evaluation for systemic and ocular adverse events. Fundus Photography and Wide field Optos fluorescein angiography will be performed at baseline and at week 20and week 52.

STUDY DURATION: Approximately 52 weeks to the end of the study. Primary endpoint will be evaluated at week 52.

Eligibility criteria: Inclusion Criteria:

A patient must meet the following criteria to be eligible for inclusion in the study:

1. Adults with Diabetes Mellitus 2. Documented history of ROTATE study completion (within 3 months +/- 1 week of exit visit) 3. BCVA ETDRS visual acuity letter score 20/25-20/400 4. Thickening due to DME involving the center of the macula evident on clinical exam 5. DME on OCT at baseline (\>305 microns if male or \>290 microns if female) as assessed on Heidelberg Spectralis SD OCT 6. At least 30 days but less than 45 days since prior 0.3 mg ranibizumab injection 7. Willing and able to comply with clinic visits and study-related procedures 8. Provide signed HIPAA statement and informed consent prior to any study procedures

-

Exclusion Criteria:

A patient who meets any of the following criteria will be excluded from the study:

1. Macular edema considered to be due to a cause other than DME (ERM, Vein Occlusion, Postop CME, uveitis)
2. History of PRP within 3 months prior to enrollment or anticipated need for PRP
3. History of idiopathic or autoimmune uveitis in the study eye
4. Cataract surgery in the study eye within 90 days of baseline
5. Any intraocular surgery within 90 days of baseline
6. Vitreomacular traction or epiretinal membrane in the study eye that is thought to affect vision
7. Clinically significant pre-retinal fibrosis involving the macula in the study eye per investigator judgment
8. Intraocular inflammation of trace or above in the study eye
9. Evidence of active infection in either eye
10. Uncontrolled glaucoma in the study eye defined as a pressure of \> 25 on maximal medical therapy.
11. Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study or could confound interpretation of the results
12. Ocular media of insufficient quality to obtain fundus and OCT images
13. Current treatment for a serious systemic infection
14. Administration of systemic anti-angiogenic agents within 180 days of screen
15. History of yag capsulotomy within 1 month prior to enrollment
16. Receipt of any treatment for DME, other than ranibizumab 0.3 mg, in the study eye at any time in the past 3 months following ROTATE study exit, (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids or other anti-VEGF agents such as Macugen, 2 mg IAI,, 0.5 mg ranibizumab, or intravitreal bevacizumab)
17. Any women who are pregnant, breast-feeding, or attempting to become pregnant
18. 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. \*\*Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Primary outcomes:
measure: Reduction in Macular Edema
timeFrame: 52 weeks from baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
Study officials:
affiliation: Southeast Retina Center, PC.
name: Dennis M Marcus, MD
role: PRINCIPAL_INVESTIGATOR
References: