VIEW 1 / VIEW 2
Citation: Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012 Dec;119(12):2537-48.
- The VIEW 1 trial was a Phase III multicenter, double-masked, randomized, parallel group, active treatment-controlled trial in the United States, and VIEW 2 trial was a similarly designed study in Europe, Asia, and Latin America, assessing the safety and efficacy of aflibercept for exudative macular degeneration
- Aflibercept dosed monthly or every two months after initial loading regimen was noninferior to monthly ranibizumab with regards to vision and anatomic outcomes
To determine the safety and efficacy of various doses and regimens of intravitreal aflibercept as compared to intravitreal ranibizumab for the treatment of nAMD.
Phase 3, multicenter, double-masked, randomized, parallel group, active treatment-controlled trials
Two primary endpoints for the studies:
- Noninferiority of any of the aflibercept regimens compared to the ranibizumab regimen as defined by the proportion of patients in each group that maintained their vision (losing <15 ETDRS letters) at week 52 of the study. Based on the existing literature, a noninferiority margin of 10% was used.
- Clinical equivalence of any of the aflibercept regimens compared to the ranibizumab regimen as defined by the proportion of patients in each group that maintained their vision (losing <15 ETDRS letters) at week 52 of the study. Based on expert opinion, a margin of 5% was used for demonstration of clinical equivalence.
Of note, the statistical analysis for each study prospectively accounted for an integrated analysis of the data from VIEW 1 and VIEW 2.
Primary endpoints were calculated using both intention-to-treat and per-protocol analyses.
Major inclusion criteria:
- Age ≥ 50 years with an active, subfoveal CNV lesion secondary to AMD (juxtafoveal lesions with leakage extending into the fovea were also included))
- CNV comprising at least 50% to total lesion size
- BCVA between 73 and 25 ETDRS letters (20/40-20/320 Snellen equivalent)
Major exclusion criteria:
- Prior treatment for exudative macular degeneration
- Subretinal hemorrhage >50% of total lesion area
- Scar, fibrosis, or atrophy involving the fovea
- Total lesion size >12 dd
- Subretinal hemorrhage in the study eye that involves the fovea
- Any history of diabetic retinopathy, diabetic edema, or other vascular diseases of the retina
RANDOMIZATION SCHEME AND INTERVENTIONS
Patients were randomized in a 1:1:1:1 ratio into one of the following treatment groups:
- 0.5 mg aflibercept q4 weeks
- 2 mg aflibercept q4 weeks
- 2 mg aflibercept q8 weeks (after 3 initial monthly treatments)
- 0.5 mg ranibizumab q4 weeks
- VIEW 1 enrolled 1217 patients
- VIEW 2 enrolled 1240 patients
In the integrated analysis, all aflibercept regimens met the prespecified margins for noninferiority and clinical equivalence using both the intention-to-treat and per-protocol analyses. Using the per-protocol analysis, the proportion of patients maintaining vision for each of the treatment groups was:
- 0.5 mg aflibercept q4 weeks 96%
- 2 mg aflibercept q4 weeks 95%
- 2 mg aflibercept q8 weeks (after 3 initial monthly treatments) 95%
- 0.5 mg ranibizumab q4 weeks 94%
Mean change in BCVA was investigated as a secondary endpoint. In the integrated analysis, all aflibercept regimens were found to be within 0.5 ETDRS letters of the ranibizumab regimen and there were no statistically significant differences among the treatment regimens.
Similarly, all anatomical endpoints and adverse events were comparable between all study regimens.
- Aflibercept, given either monthly or every 2 months (after 3 initial monthly loading doses), is equivalent to monthly ranibizumab in terms of efficacy and safety.