Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results
NCT03677934 | Archway Trial | Regillo C et al. (2023)
Regillo C, Berger B, Brooks L, et al. Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results. Ophthalmology, 2023; 130:735-747.
Locations
78 sites across the United States
Study Period
September 12, 2018 – June 23, 2021
Study Design
Phase 3, randomized, open-label, active-controlled, multicenter trial
Study Population
Experimental Group
Control Group
Follow-up Time: 96 weeks
Outcomes
Durability
Requiring supplemental ranibizumab during refill-exchange intervals
Proportion of patients not requiring supplemental ranibizumab during refill-exchange intervals:
• Refill Interval 1: 98.4%
• Refill Interval 2: 94.6%
• Refill Interval 3: 94.8%
• Refill Interval 4: 94.7%.
Treatment Exposure
Overall mean ± SD time on study (weeks):
• PDS Q24W: 96.2 ±7.43
• Ranibizumab Q4W: 94.6±15.23
No. of ranibizumab treatments per patient:
• PDS Q24W: 4.1 ±0.8
• Ranibizumab Q4W: 22.9±3.8
Vision
Best-Corrected Visual Acuity (BCVA) (primary Outcome)
Adjusted mean change from baseline in BCVA score averaged over weeks 44 and 48 (primary outcome):
• PDS Q24W: 0 (SE 0.50) letters
• Ranibizumab Q4W: 0.2 (SE 0.62) letters
• Difference: -0.2 ETDRS letters (95% CI, -1.8 to 1.3)
Adjusted mean change from baseline in BCVA score averaged over weeks 60 and 64 (primary outcome):
• PDS Q24W: -0.4 (SE 0.57) letters
• Ranibizumab Q4W: -0.8 (SE 0.69) letters
• Difference: 0.4 ETDRS letters (95% CI, -1.4 to 2.1)
Adjusted mean change from baseline in BCVA score averaged over weeks 88 and 92 (primary outcome):
• PDS Q24W: -1.1 (SE 0.61) letters
• Ranibizumab Q4W: -0.5 (SE 0.75) letters
• Difference: -0.6 ETDRS letters (95% CI, -2.5 to 1.3)
Vision Maintaining
Proportion of patients maintaining BCVA ≥69 letters at Week 96:
• PDS Q24W: 76.2%
• Ranibizumab Q4W: 77.8%
Proportion of patients losing <5 letters:
• PDS Q24W: 75.1%
• Ranibizumab Q4W: 73.5%
Proportion of patients gaining ≥5 letters:
• PDS Q24W: 26.6%
• Ranibizumab Q4W: 26.6%
Other
N/A
Immunognicity
Not reported
Pharmokinetics
PDS released ranibizumab continuously over 24 weeks, maintaining serum levels comparable to monthly ranibizumab injections.
Anatomic
Central Point Thickness (CPT)
CPT change at Week 96:
• PDS Q24W: +9.9 (SE 3.64 ) µm
• Ranibizumab Q4W: -1.3 (SE 4.48) µm
• Difference: +11.3 (95% CI, -0.1 to 22.6) µm
Central Subfield Thickness (CST)
• Generally, the mean changes from baseline in CST were within 15 µm in both arms throughout study.
• There was a trend toward an increase in CST before each refill-exchange procedure (average change up to 20 µm)
Safety
Adverse events of special interest (AESI)
Overall number of AESI :
• PDS Q24W: 103
• Ranibizumab Q4W: 20
Patients with >1 ocular AESI:
• PDS Q24W: 59 patients (23.8%)
• Ranibizumab Q4W: 17 patients (10.2%)
Ocular-related AEs
Most common: Cataract (PDS: 22 cases [8.9%], Ranibizumab: 10 cases [6.0%]).
Serious ocular AEs
• PDS Q24W: Endophthalmitis (1.6%), implant dislocation (1.6%), conjunctival erosion (4.0%), conjunctival retraction (2.4%).
Systemic AEs
Comparable between groups, with no significant safety concerns.
Conclusion
PDS Q24W was noninferior to monthly ranibizumab for BCVA at 96 weeks. Approximately 95% of PDS patients did not require supplemental treatment in each refill interval. The safety profile was generally manageable, but ocular AEs related to surgical implantation were more frequent than with intravitreal injections.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: No information on the method of the allocation concealment and the randomization.
“Baseline demographic and ocular characteristics of Archway patients have been described previously19 and were generally well balanced between arms.”
Missing Outcome Data
Some concerns
Note: The missingness was more than 5% for each of the groups. However, the proportion was balanced between the groups.
Selection of the Reported Results
Low risk Note: Registration with protocol
Deviations from Intended Observations
Some concerns Note: This is an open-label study. There is no information on whether deviations arose because of the trial context. “The efficacy and safety populations consisted of patients who received at least 1 study treatment according to the assigned treatment.” -mITT
Measurement of the Outcome
Some concerns Note: As a multicenter trial, there may be inconsistencies in outcome measurement. However, no information on the quality guarantee was supplied on the outcome assessment.
Overall
High risk
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