The Comprehensive Clinical Trials Unit at UCL



1 November 2018


A Phase I/IIa Clinical Trial of a Humanised Monoclonal Antibody Against LRG1

The Medical Research Council is funding researchers to conduct clinical trials into the use of a humanised monoclonal antibody to treat patients with age-related macular degeneration (AMD). AMD is the leading cause of severe vision loss in people over the age of 60. More than three million people in Europe and North America suffer from a neovascular form of AMD ('wet' AMD).

Current treatments involve injections which block a protein known as VEGF (vascular endothelial growth factor) which stimulates the formation of abnormal blood vessels underneath the macula (the central part of the retina) and leak fluid. Preventing the abnormal growth of blood vessels arrests the course of the disease. Unfortunately, the existing treatment doesn't work for between 10 and 15 per cent of patients and their eyesight becomes progressively worse, preventing them from being able to drive and hampering their ability to read, watch television or recognise faces easily.

A few years ago, researchers identified a different protein called LRG1 which also causes the abnormal vessel growth. The overarching aim of this project is to perform a first-in-man clinical trial of Magacizumab, a humanised monoclonal antibody against LRG1.

We will first perform a Phase I dose escalation study of a single dose of Magacizumab in up to eighteen patients with neovascular age-related macular degeneration (AMD) who are no longer responding to treatment. We will study up to 6 cohorts of 3 patients, in order to establish safety and the maximum tolerated dose. Decisions to increase the dose, remain on the same dose, or to stop will be based on the number of dose limiting events (DLEs) observed in each cohort, with a total of 6 patients treated at the Maximum Tolerated Dose (MTD).

We will then undertake a Phase IIa study in 24 patients with neovascular AMD using a combination therapy approach in which patients will receive both Magacizumab and the current standard of care (Lucentis or Eylea). Patients will be selected at the time of diagnosis and following first treatment. Patients will be randomised to active or sham injections using a 2:1 ratio of active:control in order to increase the amount of information obtained on any adverse effects of Magacizumab. Each patient will receive monthly injections for 3 months. Although the primary endpoint of the Phase IIa trial is safety and tolerability, we have designed the trial to maximize the chances of seeing clinical benefit.

These clinical trials are in set up.