This is a phase III multicenter, double-blind (double-masked), randomized, parallel group study in subjects with wAMD. Approximately 580 subjects will be enrolled and randomized in a 1:1 ratio to receive either Lucentis® (0.05 mL of 10 mg/mL ranibizumab) or the investigational product (IP), Xlucane (0.05 mL of 10 mg/mL ranibizumab), in the study eye once every 4 weeks for 52 weeks (ie, 12 months).

The study eye will be defined as the eye meeting all of the inclusion criteria and none of the exclusion criteria (ie, the enrollment criteria).

The assigned study drug will be administered as an ophthalmic intravitreal (IVT) injection. Designated, unmasked study staff will prepare and administer the study drug, ensuring that the masking of the subject is maintained during the injection procedure. See Section 8.4.6.

Subjects will be randomized by interactive web response system (IWRS) to receive 13 doses of either Xlucane or Lucentis® in the study eye. The randomization scheme will automatically ensure that the study drug assignment for a given subject is random and that an overall 1:1 ratio of assignments to each of the 2 study drug treatments is approximated. In addition, the randomization scheme will include the following stratification parameters to ensure balanced distribution of assignment to the 2 treatments: eye color (light iris vs dark iris), geographical region where enrolled and the BCVA letters at Baseline. Subjects will be followed up for changes in efficacy variables and safety for 52 weeks. Each subject’s involvement will last up to approximately 52 weeks (ie, 12 months).

At the beginning of the study, a subgroup of 60 subjects at a select number of participating sites will be sequentially asked to participate in an evaluation of PK. This subgroup will be asked to provide blood samples for measurement of serum ranibizumab immediately before administration of the first dose of Xlucane or Lucentis®. Additional samples will be collected 23 hours after the first dose (ie, Day 1) and 23 hours after the sixth dose (ie, Week 20) at expected time to maximum serum concentration (Tmax, which is around 22 hours). The primary analysis set will be the Per-Protocol population.

An interim analysis will be performed on unmasked study data. After all of the randomized subjects have 6-month (ie, 24 weeks) data available, an unmasked analysis of efficacy and safety endpoints as well as PK and immunogenicity will be performed. The aim of this analysis is to obtain results prior to completion of full follow-up for all subjects. This analysis will not affect the further conduct of the study.

FA, CFP, and OCT will performed at Screening. The images will be sent to the central reading center (CRC) for interpretation and confirmation of eligibility. The CRC will also grade images that are collected during the study.