Format

Send to

Choose Destination
Ophthalmology. 2019 Aug;126(8):1141-1154. doi: 10.1016/j.ophtha.2019.03.036. Epub 2019 Apr 1.

The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial.

Author information

1
The Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: pcampo@jhmi.edu.
2
Southeast Retina Center, Augusta, Georgia.
3
Tennessee Retina, Nashville, Tennessee.
4
Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania.
5
Genentech, Inc., South San Francisco, California.
6
Genentech, Inc., South San Francisco, California, at the time the work was completed; currently at Kodiak Sciences Inc., Palo Alto, California.
7
Genentech, Inc., South San Francisco, California, at the time the work was completed.
8
Genentech, Inc., South San Francisco, California, at the time the work was completed; currently at Seattle Genetics, Bothell, Washington.

Abstract

PURPOSE:

To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment.

DESIGN:

Phase 2, multicenter, randomized, active treatment-controlled clinical trial.

PARTICIPANTS:

Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti-vascular endothelial growth factor intravitreal injections and were responsive to treatment.

METHODS:

Patients were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 mg/ml, 100 mg/ml, or monthly intravitreal ranibizumab 0.5-mg injections.

MAIN OUTCOME MEASURES:

Time to first implant refill assessed when the last enrolled patient completed the month 9 visit (primary efficacy end point), improvement in best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety.

RESULTS:

The primary analysis population was 220 patients, with 58, 62, 59, and 41 patients in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. Median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10-mg/ml, PDS 40-mg/ml, and PDS 100-mg/ml arms, respectively. At month 9, the adjusted mean BCVA change from baseline was ‒3.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒0.5 ETDRS letters, +5.0 ETDRS letters, and +3.9 ETDRS letters in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. At month 9, the adjusted mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms. The optimized PDS implant insertion and refill procedures were generally well tolerated. After surgical procedure optimization, postoperative vitreous hemorrhage rate was 4.5% (7/157; 1 event classified as serious). There was no evidence of implant clogging.

CONCLUSIONS:

In the phase 2 Ladder trial, the PDS was generally well tolerated and demonstrated a dose response across multiple end points in patients with nAMD. The PDS 100-mg/ml arm showed visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5-mg injections but with a reduced total number of ranibizumab treatments. The PDS has the potential to reduce treatment burden in nAMD while maintaining vision.

PMID:
30946888
DOI:
10.1016/j.ophtha.2019.03.036
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center