Clinical Drug Experience Knowledgebase

Prospective Optical Coherence Tomography (OCT) Imaging of Patients With Neovascular Age-Related Macular Degeneration (AMD) Treated With Intra-Ocular Lucentis™ (Ranibizumab): PrONTO Study

This is a Phase II, open-label study of intravitreally administered ranibizumab (LucentisTM). Ranibizumab is an anti Vascular Endothelial Growth Factor (VEGF) antibody fragment. Approximately 40 subjects with primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) will be enrolled. Lesion types included will be minimally classic or occult (predominatly occult) lesions or predominantly classic CNV, if the patient had received prior PDT (no more than 3 treatments). The study will be conducted at one study site.

After reading the informed consent and having all their questions answered by the investigator and the coordinator, the subjects will sign the informed consent prior to participation in a screening period that could last up to 28 days to determine eligibility. Fluorescein angiograms (FA) will be used to determine CNV classification for study eligibility. In addition, optical coherence tomography (OCT) will provide information on retinal thickness, subretinal fluid and sub retinal pigment epithelium fluid for study eligibility. Fluorescein angiograms and OCT will be evaluated by the Bascom Palmer Reading Center. OCT images will be evaluated primarily using the standard Zeiss Stratus OCT software (Vers. 3) to determine study eligibility and retinal thickness. Proprietary software algorithms in development and not yet validated by the FDA may be used for future data analysis but will not be included in the intial data analysis. The angiographic features that will permit participation will include evidence of CNV with subfoveal involvement of the lesion. The OCT features that will permit participation will include retinal thickness (macular edema) ≥300 microns, subretinal fluid ≥100 microns in thickness, or a detachment of the retinal pigment epithelium ≥100 microns in thickness. ETDRS visual acuity measurements must be between 20/40 and 20/400.

All eligible subjects will receive a ranibizumab dose of 500 micrograms at baseline and every 30 days thereafter for the first two months. ETDRS visual acuity testing and OCT measurements will be performed prior to injection. After each of the first 3 injections (baseline, Month-1, and Month-2), patients will return on post-injection days 1, 2, 4, 7, and 14. OCT measurements will be performed at those visits. ETDRS visual acuity measurements will be performed on each injection day and on post-injection day #14. At the Month-3 follow-up exam and thereafter, if the vision is stable or improved (stable visual acuity score= ±4 letters; improved visual acuity score ≥ 5 letters) from the previous visit, and there is no evidence of leakage from CNV as determined by fluorescein angiography and OCT, then no injection will performed. If the previous criteria are not met, then injections are continued monthly until these criteria are fulfilled. At that point, no further injections will be given until there is evidence of recurrent CNV.

Enrolled subjects, who did not have predominantly classic CNV at baseline but converted to predominantly classic CNV within the study, will be offered veteporfin photodynamic therapy (PDT). If a patient receives PDT, there will be no injection of ranibizumab at that visit, and the next injection of ranibizumab will not be performed for at least 1 month. Patients will continue in the study and receive additional PDT at 3 months intervals if needed. There will alaways be at least a 1 month separation between PDT and the subsequent ranibizumab injection.

The following criteria will need to be fulfilled to resume injections. There will need to be evidence of vision loss ≥ 5 letters associated with evidence of leakage from CNV as determined by OCT or fluorescein angiography, or a new-onset macular hemorrhage, or new onset classic CNV, or an increase in central macular thickness ≥ 100 microns.

Only one eye will be chosen as the "study eye". Only the study eye will receive intravitreal injections of ranibizumab.

Subjects will have scheduled monthly visits throughout the study for the evaluation of safety and efficacy. Subjects will have the first treatment of a ranibizumab injection by the injecting physician on Day 0 and will undergo retinal analysis by OCT on Days 1, 2, 4, 7 and 14 after the first 3 study treatments. At subsequent visits (every month [30±7 days]), the subject will have a safety evaluation by the evaluating physician prior to possible retreatment. After months 3 subjects will be contacted by the site personnel 2 days (±1 day) after each study treatment to elicit reports of any decrease in vision, eye pain, unusual redness, or any other new ocular symptoms; subjects will also be asked whether they have taken the prescribed self-administered post-injection antimicrobials. During the first 3 months, these questions will be asked when they return to clinic. Every 3 months, subjects will undergo fluorescein angiography and color fundus photography. Subjects will have a final safety visit at Month 24.

Fundus photography and fluorescein angiography will be performed at baseline and at months 3, 6, 12, 18, and 24. Additional fluorescein angiography will be performed at visits when it is decided that injections should be stopped (if continued past Month-3) or be resumed due to decreased vision and possible evidence of leakage from CNV. Optical coherence tomography will be performed at baseline and on days 1, 2, 4, 7, 14 after each of the first 3 injections. Since preliminary data suggest that OCT imaging can detect the earliest manifestations of recurrent CNV, all patients will be monitored once injections have been stopped using monthly ophthalmologic exams, ETDRS visual acuity measurements, and OCT imaging at each monthly follow-up visit up to month 24.