Session Title: Free Papers Moved to Main Sessions
Session Date/Time: Saturday 09/09/2017 | 00:00-00:00
Paper Time: 12:15
Venue: Forum Auditorium
First Author: : M.C.Gillies AUSTRALIA
Co Author(s): : A.P. Hunyor J.J. Arnold F.L. Pecheur K.M. Underhill R.H. Guymer I.L. McAllister
Since ranibizumab and aflibercept have different biologic characteristics, their association with the risk of development of Geographic Atrophy (GA) in eyes with neovascular Age-Related Macular Degeneration (nAMD) may differ. The purpose of the RIVAL study is to compare the rate of development of GA after 24 months in nAMD patients treated with 0.5 mg ranibizumab and 2.0 mg aflibercept using a ‘Treat and Extend’ regimen (T&E). The primary endpoint of the study is the mean change in area of GA from baseline to Month 24.
RIVAL is a 24-month, randomised, multi-centre Phase IV study that is being conducted in Australia. Results from a 12-month interim analysis of pre-specified key secondary endpoints (number of injections and change in Best Corrected Visual Acuity (BCVA) from baseline to Month 12), are presented here.
Eligibility criteria included visual impairment (≥23 letters on a Logarithm of Minimal Angle of Resolution (LogMAR) chart) due to nAMD in at least one eye without prior treatment. Eyes were randomised (1:1) to receive intravitreal injections of either 0.5 mg ranibizumab (RBZ) or 2.0 mg aflibercept (AFL). BCVA assessors and the Central Reading Centre (CRC) were masked to treatment assignments. After receiving three initial monthly injections, patients entered the T&E phase which allowed for extension up to 12-weekly injections by 2 weekly increments if the CNV was considered inactive as per protocol. The pre-planned 12-month interim analysis was based on the Full Analysis Set, comprising of all randomised patients who had at least one post-baseline efficacy value for the primary endpoint. Missing data were not imputed. The mean change in BCVA from baseline at Month 12 was analysed using a mixed model. The number of injections from baseline to Month 12 was analysed using a Negative Binomial Model, with follow-up period as an offset variable.
Of the 281 patients randomized into the study, 278 patients were included in the Full Analysis Set (98.9%; n=141 in RBZ arm; n=137 in AFL arm). Demographics and baseline characteristics were comparable between the two arms. The mean BCVA at baseline was 65.3 letters in the RBZ arm (n=141 [23-90]) and 65.1 letters in the AFL arm (n=137 [23-89]). The mean BCVA at Month 12 for completers was 72.9 letters in the RBZ arm (n=127, SD=15.5 [5-95]), and 70.5 letters in the AFL arm (n=121, SD=14.6 [36-91]). When applying a random effects mixed model which uses all observed values including withdrawals, the change from baseline at Month 12 was assessed to be +6.93 (95% CI: 5.20 to 8.65) for RBZ and +4.41 (95% CI: 2.64 to 6.18) for AFL. In patients who withdrew from the study before Month 12, the mean BCVA at the time of withdrawal [mean change from baseline] was 66.1 letters [+7.1] for RBZ (n=14; 9.9%) and 64.8 letters [+2.0] for AFL (n=16; 11.7%). The mean number of injections from baseline to Month 12 was 9.7 injections in both the RBZ (n=141; SD=2.77 [1-13]) and AFL arms (n=137; SD=2.55 [3-13]).
RIVAL is the first randomized clinical study to compare ranibizumab and aflibercept in nAMD patients when both are used with an identical T&E dosing regimen. Significant visual acuity improvements were achieved by Month 12 with both ranibizumab (+6.93 letters) and aflibercept (+4.41 letters), with similar mean number of injections received over the first 12 months period. The results from this pre-planned 12-month interim analysis conducted on key secondary efficacy endpoints demonstrate that the study arms are well balanced with regards to baseline characteristics, and that ranibizumab and aflibercept are both effective treatments for nAMD when used in a T&E regimen.