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?

Age-related macular degeneration (AMD) causes blurred or reduced central vision in one or both eyes. There are two forms of AMD. They depend on how the back of the eye (known as the retina) is damaged. They are called ‘dry AMD’ and ‘neovascular AMD’ or ‘wet AMD’. In wet AMD, a protein called VEGF makes abnormal blood vessels form in the centre of the retina (‘macula’). This can leak fluid onto the back of the eye and affect central vision. Wet AMD can be treated by injecting an anti-VEGF drug (e.g. ranibizumab), into the eye. This injection can be given as often as every 1-2 months. Many people find this a burden. The Port Delivery System (PDS) is an eye implant device. It can release ranibizumab into the eye continuously over time and be refilled. 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. It will be refilled either every 6 months or every 9 months. The trial includes people with wet AMD.

2. How does the Velodrome clinical trial work?

This clinical trial is recruiting people with wet AMD. 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 for wet AMD within the last 6 months, and have responded to anti-VEGF treatment before joining the trial. People who have not been treated with anti-VEGF injections can still take part.

The clinical trial is split into two phases. People who take part in this clinical trial (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 have not needed extra injections of ranibizumab into the eye (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 of the clinical trial. The second phase will last 12 months. During the second phase, participants will be given either two PDS ranibizumab refills (every 6 months) or a single refill at 9 months after the start of the trial.

The clinical trial doctor will see participants every month during the trial. Hospital visits will include eye and general health checks, the participants response to the treatment, and any side effects they may have. Participants will also occasionally receive follow-up calls to check on their health following a hospital visit. The total time of participation in the clinical trial will be about a year and a half. Participants can stop trial treatment and leave the clinical trial at any time. At the end of the trial, participants can decide with the clinical trial doctor whether to continue to be given PDS ranibizumab refills in an extension of this trial (called Portal). If they do not continue to be given PDS refills, participants can choose to have the PDS removed from their eye or leave the PDS implant 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
  • with improved or worsened best-corrected vision scores
  • who prefer receiving treatment with the PDS compared with injections into the eye
  • who do not need a ranibizumab injection into the eye at 4 and/or 5 months
• How satisfied participants are with treatment
• How the body processes and responds to ranibizumab
• The number and seriousness of any side effects

4. Who can take part in this clinical trial?

People can take part in this trial if they are aged over 50. They must have at least 20/200 best-corrected vision and no scarring caused by wet AMD., Participants eyes will need to be clear enough so that photographs of the back of their eyes can be taken. Their vision must be tested before having anti-VEGF treatment.

People may not be able to take part in this trial if they have had some treatments for wet AMD before (not including some anti-VEGF treatment). Or if they have been involved in another clinical trial for wet AMD. People who have had eye surgery or implants or have a recent history of medical conditions like stroke, heart problems, or cancer cannot take part. Neither can people who are pregnant or breastfeeding. This applies during the clinical trial and within 1 year after.

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

Everyone who joins this clinical trial will have the PDS with ranibizumab surgically inserted into one eye under anaesthetic. This will happen on Day 1 of the first phase of the trial. In the second phase of the trial, 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 will have a 1 in 2 chance of being placed in either group. The second phase will only include those who did not need injections of ranibizumab into the eye 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 or use 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 in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).

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

Participants may have side effects (an unwanted effect of a drug or medical treatment) 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 will be performed regularly. Participants will be told about the known side effects of ranibizumab and the PDS, and possible side effects based on human and laboratory studies or knowledge of similar drugs and devices. Participants will be told about any known side effects of the surgical eye implant and PDS refill procedures and injections into the eye and, where relevant, potential side effects based on human and laboratory studies or knowledge of similar 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.

For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04657289

Trial-identifier: NCT04657289