Diabetic Retinopathy
Conditions
Brief summary
The VOYAGE trial will assess diabetic retinopathy severity scale (DRSS) levels, through 112 weeks, while being managed with aflibercept as needed, among subjects who completed the 2-year PANORAMA trial (VGFTe-OD-1411) and were treated in a clinical setting prior to joining the VOYAGE study.
Detailed description
This phase 4 study is designed to assess the need for ongoing 2 mg intravitreal aflibercept injections (IAI) for subjects who completed the 2-year PANORAMA (VGFTe-OD-1411) trial for the management of diabetic retinopathy (DR). Sites will be considered for VOYAGE if they have 4 or more subjects from PANORAMA able to participate. Relevant data from all participating subjects will be collected and reported retrospectively for the period between PANORAMA study exit and VOYAGE study enrollment. For the prospective portion of the study, eyes will be assigned to 1 of 2 groups, eyes without panretinal photocoagulation (PRP) and eyes with PRP. Group 1: Subjects with study eyes without PRP will be seen every 16 weeks (Q16W) and treated with IAI on a flexible treatment regimen based on their DRSS level. An injection will be given at each 16-week visit when the DRSS level is 47 or worse. If the DRSS level is better than 47, for example level 43 or 35, the study eye will not be treated. DRSS level will be determined by the investigator, based on ophthalmic exam and fundus photography (FP) compared to prior imaging when available. Every 8 week visits can be performed under specific circumstances: * If a subject has a 2-step DRSS level worsening compared to the last protocol-scheduled 16-week visit (for example the week-16 or week-32 visit) and/or the DRSS level is 53 or worse OR * If a subject has active proliferative DR (PDR) Under both of these circumstances, IAI will be administered as scheduled and the subject can be seen and treated every 8 weeks (Q8W) with IAI. Under both of these circumstances, Q8W visits and Q8W IAI treatments can be continued until there is no active PDR and the DRSS improves to the level observed at the visit before the subject began being seen at 8-week intervals. Group 2: Subjects with study eyes with PRP will be seen Q16W and treated with IAI on a flexible treatment regimen based on activity of the neovascular disease process as assessed by the treating investigator based on ophthalmic exam and/or FP compared to prior imaging when available. If the neovascular disease is inactive, no treatment will be given. If the neovascular disease is active and stable (not new or worse), the subject will be treated with intravitreal (IVT) IAI at the Q16W interval. If new or worsening neovascular disease develops, subjects may be seen and treated Q8W until the neovascular disease is stable or inactive at which time the interval between visits will increase to 16 weeks. Subjects in both groups will be evaluated for efficacy, using best corrected visual acuity (BCVA) using the 4-meter ETDRS protocol with normal-luminance, Humphrey Visual Field (HVF), National Eye Institute (NEI) Visual Function Questionnaire (VFQ) 25, spectral domain optical coherence tomography (SD-OCT), optical coherence tomography angiography (OCT-A), FP, and fluorescein angiography (FA), and for ocular and systemic safety (including ophthalmic exams and laboratory assessments) through week 112. Subjects who develop new or worsening PDR, including anterior segment neovascularization (ASNV), or center-involved DME may qualify for rescue treatment.
Interventions
Intravitreal 2mg aflibercept injection
Sponsors
Regeneron Pharmaceuticals
Clinical Trials Resource Group, LLC
Greater Houston Retina Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Enrolled and completed PANORAMA (VGFTe-OD-1411) clinical trial 2. Willing and able to comply with clinic visits and study-related procedures 3. Provide signed informed consent
Exclusion criteria
1. Any prior systemic anti-vascular endothelial growth factor (VEGF) treatment or IVT anti-VEGF treatment in the study eye within 21 days of baseline 2. Any intra- or periocular corticosteroid treatment in the study eye within 3 months of baseline 3. Any intraocular sustained-release treatment, implantable device, or gene therapy in the study eye 4. Pregnant or breastfeeding women 5. 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/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 amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DRSS Level Achievement in the VOYAGE study | 112 weeks | Proportion of subjects achieving a DRSS level of 43 or less in the VOYAGE study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DRSS Level Improvement | 112 weeks | Proportion of subjects with stable, worsened, or improved DRSS level from baseline to week 48 and baseline to week 112 compared to the DRSS at the baseline of the VOYAGE trial and the DRSS at the last visit of the PANORAMA trial. |
| Injection Frequency | 112 weeks | Mean and median number of IVT aflibercept injections (with and without IAI given for DME) |
| Subjects without Treatment | 112 weeks | Proportion of subjects receiving 0 injections |
| PDR Events | 112 weeks | Percentage of subjects over time who develop a new PDR event |
| Center-Involved Diabetic Macular Edema Development | 112 weeks | Percentage of subjects over time who develop center-involved (CI) DME |
| DRSS Level Achievement in the PANORAMA study | 112 weeks | Proportion of subjects achieving a DRSS level of 43 or less from the completion of the PANORAMA study |
| Change in Central Retinal Thickness | 112 weeks | Mean change in central retinal thickness from baseline |
| Change in Area of Nonperfusion | 112 weeks | Change in total area of retinal capillary non-perfusion from baseline |
| Changes in Visual Function (HVF) | 112 weeks | Changes in visual function outcomes from Humphrey Visual Field from baseline |
| Changes in Visual Function | 112 weeks | Changes in visual function outcomes NEI VFQ-25 from baseline |
| Incidence of Adverse Events | 112 weeks | Incidence and severity of ocular and systemic adverse events from baseline |
| Change in Visual Acuity | 112 weeks | Mean change in ETDRS BCVA from baseline |
Countries
Puerto Rico, United States
Outcome results
None listed