A clinical trial to look at how an eye implant that continuously releases ranibizumab works to reduce certain signs of wet age-related macular degeneration, how safe the eye implant and ranibizumab are, and how the body gets rid of and responds to ranibizumab

1. Why is the Velodrome clinical trial needed?

Wet age-related macular degeneration (AMD) causes blurred or worse vision in one or both eyes. In wet AMD, a protein called VEGF makes abnormal blood vessels form in the central retina (‘macula’), which can leak fluid and affect central vision. Wet AMD can be treated by injecting an anti-VEGF drug (e.g. ranibizumab) into the eye, and can be given up to every 1-2 months. Many people find this a burden. The Port Delivery System (PDS) is a refillable eye implant device that releases ranibizumab into the eye continuously over time. The PDS can remain in the eye long-term unless removed for health reasons. This clinical trial aims to assess the effects, good or bad, of ranibizumab delivered by the PDS, in people with wet AMD. It will be refilled either every 6 months or 9 months.

2. How does the Velodrome clinical trial work?

People can take part if they were diagnosed with wet AMD within the last 9 months, have previously been treated with at least three anti-VEGF injections within the last 6 months, and responded to anti-VEGF treatment before the trial. People not yet treated with anti-VEGF injections can still take part. 

The clinical trial is in two phases. People taking part (participants) will be given the clinical trial treatment ranibizumab with the PDS eye implant. The PDS will be surgically inserted into the affected eye on Day 1 of the first phase. After 6 months, participants who didn’t need extra eye injections of ranibizumab (at 4 and/or 5 months after first being given the PDS), or their wet AMD activity meets certain criteria at 6 months, can join the second phase. The second phase will last 12 months, and during this, participants will be given either two PDS ranibizumab refills (every 6 months) or one refill at 9 months after the start of the trial. 

Participants will see the clinical trial doctor every month. Hospital visits include eye and general health checks, the participant’s treatment response, and any side effects they may have. Participants will occasionally receive follow-up calls to check on their health. The total time of trial participation will be about 1.5 years. Participants can stop trial treatment and leave the clinical trial at any time. At the end, participants can decide with the clinical trial doctor to continue having PDS ranibizumab refills in an extension of this trial (called Portal). If they do not continue, participants can choose to have the PDS removed or leave it in their eye long-term.

3. What are the main endpoints of the Velodrome clinical trial?

The main clinical trial endpoint (the main result measured in the trial to see if the drug and device have worked) is the average change in the best eyesight a person can have when wearing glasses or contact lenses – known as ‘best corrected vision’ – at 15 and 16 months compared with the start of the trial. 

The other clinical trial endpoints include:

• The change in vision test score and thickness of the back of the eye over the whole trial
• The number of participants with very good or poor best-corrected vision scores
• The number of participants who prefer treatment with the PDS compared with eye injections
• The number of participants who do not need ranibizumab eye injections at 4 and/or 5 months
• The number and seriousness of any side effects

4. Who can take part in this clinical trial?

People aged over 50, 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 photo’s 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 trial and 1 year after.

5. What treatment will participants be given in this clinical trial?

Everyone in this clinical trial will have the PDS with ranibizumab surgically inserted into one eye under anaesthetic, on Day 1 of the trial. In the second phase, some participants will be split into two groups randomly (like flipping a coin) and given either:

• Group 1: one PDS ranibizumab refill at 9 months from the start of the trial
• Group 2: two PDS ranibizumab refills at 6 and 12 months from the start of the trial

Participants have a 1 in 2 chance of being placed in either group. The second phase only includes those who did not need eye injections of ranibizumab at 4 and/or 5 months. Or, their wet AMD activity meets certain criteria at 6 months.

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment may not be fully known at the time of the trial. Most trials 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 who would like to participate will be told about any risks and benefits of taking part, as well as other procedures, tests, or assessments in the trial. All these will be described in an informed consent (a document that provides people with the information they need to decide to volunteer for the trial). 

Risks associated with the clinical trial drugs, devices, or procedures

Participants may have side effects from the drugs, devices, or procedures used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments are performed regularly. Participants will be told about the known side effects of ranibizumab and the PDS, the surgical eye implant and PDS refill procedures and injections into the eye, and possible side effects based on human and laboratory studies or knowledge of similar drugs, devices and procedures. 

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.