Fluid Control in Neovascular Age-Related Macular Degeneration with Brolucizumab: An Analysis of the HAWK and HARRIER Phase 3 Trials
NCT02307682 NCT02434328 | HAWK & HARRIER | *Regillo C et al. (2022)
Regillo, C., Singh, R., Hamilton, R., Gedif, K., Best, C., Koh, A., Holz, F. G. Fluid Control in Neovascular Age-Related Macular Degeneration with Brolucizumab: An Analysis of the HAWK and HARRIER Phase 3 Trials. Ophthalmologica, 2022; 245:403–412.
Locations
271 sites across 20 countries worldwide
Study Period
• HAWK: December 2014 to May 2016 • HARRIER: June 2015 to April 2016
Study Design
Post hoc analysis of two phase 3, multicenter, randomized, double-masked trials
Study Population
Experimental Group
Control Group
Follow-up Time: 96 weeks
Outcomes
Durability
Time to Achieve Sustained Dryness
• HAWK: Brolucizumab achieved dryness ~24–32 weeks earlier with 1.8–2.1 fewer injections than aflibercept
• HARRIER: Brolucizumab achieved dryness ~20–28 weeks earlier with 2.0–2.6 fewer injections than aflibercept
Vision
Best-Corrected VA (BCVA)
Mean BCVA Change from Baseline to Week 48 (Primary Outcome of the project):
(See details in Dugel P et al. 2020)
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Fluid Assessment (Primary Outcome of this paper)
Intraretinal fluid (IRF) and subretinal fluid (SRF) resolution at Week 96:
• HAWK: Brolucizumab = 76.1%, Aflibercept = 63.1% (p = 0.0002)
• HARRIER: Brolucizumab = 75.4%, Aflibercept = 61.8% (p < 0.0001)
Residual fluid (IRF and/or SRF) from baseline to Week 96:
• More patients treated with aflibercept had residual fluid (IRF and/or SRF) at any point than patients treated with brolucizumab.
Sustained Dryness
At Week 96:
• HAWK: Brolucizumab = 86.1%, Aflibercept = 82.0% (p ≤ 0.01)
• ARRIER: Brolucizumab = 91.2%, Aflibercept = 78.0% (p < 0.0001).
Safety
Safety data have previously been presented in detail for HAWK and HARRIER (Dugel P et al. 2020 & Dugel P et al. 2021). The incidence of ocular adverse events was similar across all treatment groups in both HAWK and HARRIER up to week 96, except intraocular inflammation (IOI) (Dugel P et al. 2021).
Conclusion
Brolucizumab demonstrated superior fluid control compared to aflibercept, achieving faster and more sustained dryness with fewer injections. This suggests a potential for reducing the treatment burden in patients with nAMD.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “The Interactive Response Technology [IRT] assigned a randomization number to the patient that was used to link the patient to a treatment arm and specified a unique medication number for the first package of study treatment to be administered to the patient. The randomization number was not communicated to unmasked staff.” “No clinically meaningful differences in demographics and baseline ocular characteristics were observed in either trial.”
Missing Outcome Data
High risk
Note: This is a post hoc analysis. No information was supplied about if the missingness depends on true value.
Selection of the Reported Results
Low risk Note: Registration with the protocol
Deviations from Intended Observations
Low risk Note: This is a double-masked study. ITT principle was applied for the primary outcome: “Fluid status (yes/no) with 95% confidence intervals was assessed based on the full analysis set (FAS) with last observation carried forward imputation.”
Measurement of the Outcome
Low risk Note: This is a double-masked study. “All anatomic assessments (qualitative for fluid assessments and quantitative for CST assessments) were conducted at a masked central reading center.”
Overall
High risk
Categories: Wet AMD