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

Characteristic:

Type of AMD:

2 (Wet AMD)

AMD Stage:

3 (Late)

Total Sample Size:

415 patients

Age:

Phase 3, randomized, open-label, active-controlled, multicenter trial

Sex (Male) n%:

Not explicitly reported

Experimental Group

Intervention Therapy:

Port Delivery System (PDS) with ranibizumab 100 mg/ml, refilled every 24 weeks

Dose & Frequency:

Surgically implanted device for continuous delivery, refilled every 24 weeks (Q24W)

Age (Years):

75.0 ± 7.9 years

Number of Patients:

248 randomized and treated

Male N %:

103 (41.5%)

Patients Followed Up:

224 (90.3%)

Control Group

Intervention Therapy:

Intravitreal ranibizumab 0.5 mg monthly injections

Dose & Frequency:

Ranibizumab 0.5 mg Q4W (every 4 weeks)

Age (Years):

75.0 ± 7.9 years

Number of Patients:

167 randomized and treated

Male N %:

67 (40.1%)

Patients Followed Up:

154 (92.2%)

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.

Outcomes

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