A study to assess the effectiveness and safety of the Port Delivery System with ranibizumab in participants with neovascular age-related macular degeneration

1. Why is this study needed?

Neovascular age-related macular degeneration (nAMD)/ wet AMD is a condition where abnormal blood vessels grow in the central part at the back of the eye, causing swelling, bleeding, and potential vision loss. Vascular endothelial growth factor (VEGF), a protein that promotes blood vessel growth, is believed to contribute to the formation and leakage of these vessels. Wet AMD can be treated by regularly injecting medicine directly into the affected eye which blocks the effects of VEGF (called anti-VEGF, for example, ranibizumab). However, in the real world, because treatment is demanding and hard to keep up with, people often don’t get treated as often as needed, leading to less effective results. Therefore, there is a need for treatments that require less frequent dosing while still providing consistent benefits.

This study is testing a device (including an eye implant) known as the Port Delivery System with ranibizumab (PDS). This implant slowly releases ranibizumab into the eye over a prolonged period to treat wet AMD. PDS is approved in the United States, however, it is yet to be approved for the treatment of wet AMD in other countries and may be considered an experimental drug and device. This study aims to assess the safety and effects of PDS in participants with wet AMD. The implant is intended to remain life-long in the eye unless removed for medical reasons.

2. Who can take part in the study?

People aged over 50 years, within 2 years of their initial wet AMD diagnosis, with at least 20/200 best-corrected vision and no scarring caused by wet AMD can take part. Participants' eyes must be clear enough so photos of the back of their eyes can be taken. Their vision must be tested before having anti-VEGF treatment. People may not take part if they have had some treatments for wet AMD before (not including some anti-VEGF treatment), or if they were involved in another wet AMD clinical trial. People who had eye surgery or implants or a recent history of conditions like stroke, heart problems, or cancer, and people who are pregnant or breastfeeding cannot take part. This applies during the clinical study and 1 year after.

3. How does this study work?

People will be screened to check if they can participate in the study. After the screening visit, one eye of the participant will be chosen as the ‘study eye’ for placing the implant. The implantation will take place within 7- 35 days after the last anti-VEGF treatment received by the participant. The implant will be placed in the study eye through a surgical procedure on Day 1. The implant will be refilled with ranibizumab either every 9 months or every 6 months depending on how the disease is progressing in the first 6 months. Participants who do not have the desired effect may receive extra ranibizumab as an injection in the eye (intravitreal).

During this study, the study doctor will see the participants 1 day, 1 week, and then 1 month after the implant surgery. After the 1-month visit, the study doctor will see participants every 1 or 2 months until the first refill and then every 1, 2, or 3 months until the end of the study. These visits will be to see how well the treatment is working. Total time of participation in the study will be about 19 months. Participants have the right to stop study treatment and leave the study at any time if they wish to do so.

4. What are the main results measured in this study?

The main result measured in the study is to assess change after treatment in a person's best eyesight when using glasses or contact lenses, known as ‘best-corrected vision’ over 17 and 18 months compared with the start of the trial. This is assessed using an ETDRS chart that looks at how much better or worse the eyesight is by looking at it before and after treatment. Other key results measured in the study include:

• Change in vision test score and thickness of the back of the eye over the whole study
• Number of participants who after treatment lose significant vision or show no improvement
• Number of intravitreal ranibizumab injections participants received and number of study visits in each refill cycle (time between two refills)
• Number of participants who prefer PDS compared with eye injections and who do not undergo treatment with ranibizumab eye injections before each refill procedure
• Number and seriousness of any unwanted effects

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not improve participant's eyesight. But the information collected in the study can help other people with similar health conditions in the future. Most studies involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options for treatment.

Risks associated with the study drug and device and procedures
Participants may have unwanted effects of the drugs, devices, and procedures used in this study. These unwanted effects can be mild to severe, or vision-threatening, and vary from person to person.

Ranibizumab
Known unwanted effects include inflammation in the eye (vitritis), swelling and inflammation of the eyelids (blepharitis), bleeding in the back of the eye (retinal haemorrhages), visual disturbances, redness of the eye and itchy eye and small particles or spots in your vision (vitreous floaters). The study medicine may be harmful to an unborn baby. Women must take precautions to avoid exposing an unborn baby to the study treatment.

PDS
Known unwanted effects include dislocation (movement) of the eye implant which may lead to loss of fluid from the inside of the eye (vitreous fluid leak), decrease in eye pressure (hypotony), separation of one of the layers in the back of your eye (retinal detachment or choroidal detachment), perforation of the eyeball (open globe) or clouding of the lens in your eye (cataract), infection of the eye (endophthalmitis).