Clinical Studies:
PANORAMA
Citation: National Library of Medicine (U.S.). (2016, March – 2020, July ). A Phase 3, Double-Masked, Randomized Study of the Efficacy and Safety of Intravitreal Aflibercept Injection in Patients With Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (PANORAMA). Identifier NCT02718326. https://clinicaltrials.gov/ct2/show/results/NCT02718326
Key Points
- PANORAMA was the first phase 3 randomized, clinical trial intentionally designed to evaluate the efficacy and safety of intravitreal (IVT) anti-VEGF therapy in patients with moderately severe to severe nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME).
- Sponsored by Regeneron Pharmaceuticals, the trial compared patients receiving sham injection to patients receiving 1 of 2 aflibercept dosing regimens, with primary endpoints at 24 weeks and 52 weeks.
- Patients receiving aflibercept resulted in regression of NPDR, demonstrated by improvement by ≥2 Steps from baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at both 24 weeks and 52 weeks.
- Significant secondary outcomes included less vision threatening complications (such as proliferative diabetic retinopathy (PDR) and anterior segment neovascularization (ASNV)) and less development of DME in patients who received aflibercept injections, regardless of dosing regimen.
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Objective
To evaluate the efficacy of IVT aflibercept compared to sham treatment in the improvement of moderately severe to severe NPDR.
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STUDY DESIGN
Randomized, multi-center, double-masked, phase 3, interventional clinical trial.
STUDY SUBJECTS
- Men or women ≥ 18 years old with type 1 or 2 diabetes who have moderately severe to severe NPDR (diabetic retinopathy severity scale (DRSS) levels 47 or 53), in whom panretinal photocoagulation (PRP) can be safely deferred for at least 6 months
- Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥ 69 letters (approximate Snellen equivalent of 20/40 or better).
Inclusion criteria:
- DME threatening center of macula in study eye
- Presence of retinal neovascularization on clinical exam or FA
- Prior focal/grid laser photocoagulation or prior PRP in study eye
- Prior systemic or IVT anti-VEGF treatment in the study eye
- Prior intraocular steroid injection in study eye
- Any current anterior segment neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at screening assessment
Major exclusion criteria:
RANDOMIZATION SCHEME AND INTERVENTIONS
Subjects who met the inclusion criteria were randomly assigned in a 1:1:1 ratio stratified based on their Diabetic Retinopathy Severity Scale (DRESS) score to:
- Sham injection treatment: sham IVT injection in the study eye every 4 weeks (Q4) to week 16 (after 5 initially monthly sham injections), followed by sham injections Q8 to week 96
- Intravitreal Aflibercept Injection 2Q8: 2 mg in study eye every 8 weeks from day 1 to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with 2 mg to week 96
- Intravitreal Aflibercept Injection 2Q16: 2 mg in the study eye every 16 weeks (after 3 initial monthly doses and one 8-week interval) to week 96
Outcomes:
Study population:
- 402 patients overall
- Completion rate: sham 73%, aflibercept 2Q8 83.6%, aflibercept 2Q16 82.2%
Primary Outcomes:
- Improvement of ≥2 step in DRSS score from baseline at week 24
- 55.1% of aflibercept 2Q8 vs. 61.2% of aflibercept 2Q16 vs. 6% sham injection
- Improvement of ≥2 step in DRSS score from baseline at week 52
- 79.9% of aflibercept 2Q8 vs. 65.2% of aflibercept 2Q16 vs. 15% sham injection
Secondary Outcomes:
- Development of vision-threatening complication due to diabetic retinopathy (such as PDR and ASNV) at week 52
- 3% of aflibercept 2Q8 vs. 3.7% of aflibercept 2Q16 vs. 20.3% sham injection
- Development of Central Involved-Diabetic Macular Edema (CI-DME) at Week 52
- 8.2% of aflibercept 2Q8 vs. 6.7% of aflibercept 2Q16 vs. 25.6% sham injection
- Participants who received PRP inclusive of patients undergoing vitrectomy with endolaser by week 52
- 0.7% of aflibercept 2Q8 vs. 0.7% of aflibercept 2Q16 vs. 6.8% sham injection
- Area Under the Curve (AUC) for change from baseline in BCVA at week 52
- 1.3 (SD3.49) for aflibercept 2Q8 vs. 1.7 (SD 3.5) for aflibercept 2Q16 vs. 0.5 (SD 3.01) for sham injection (no significant difference between 2Q8 group vs. sham but significant difference between 2Q16 vs. sham)
CONCLUSIONS
- In this randomized clinical trial, intravitreal aflibercept with two different dosing regimens was shown to be statistically superior to sham injection demonstrated by improvement of ≥2 steps from baseline in the DRSS score at 24 and 52 weeks.