Results of a Phase II study of a complement c3 inhibitor for the treatment of geographic atrophy have been deemed sufficiently positive to proceed with a 600 particpant Phase III clinical trial. According to the study sponsor (Apellis, a US pharmaceutical company), the experimental drug, “APL-2” met a primary endpoint of reducing the growth rate of the geographic atrophy (GA) lesion compared to a sham injection after 12 months of treatment. The drug, a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer specifically targeting C3 and C3b, was administered monthly via intravitreal injection. The inhibitor was reported to show a 29% (p=0.008) reduction in the rate of GA lesion growth compared to sham after 12 months of treatment. While administration of the drug every second month showed a 20% (p=0.067) reduction. The sponsor stated that statistical significance for the study was defined as p<0.1 but it was not clear why this was increased from the standard statistical significance of p<0.05.
The interventional study formally entitled, “a Phase II, prospective, multicenter, randomized, single-masked, sham-controlled study to assess the safety, tolerability and evidence of activity of multiple IVT injections of APL-2 in subjects with GA associated with Age-Related Macular Degeneration”, was a 246 patient trial carried out in 35 locations in the US, Austrailia and New Zealand. Study subjects recrutied to the trial were randomized in a 2:2:1:1 manner to receive the drug monthly, every second month, sham monthly or sham every second month, respectively for a 12 month period. After the 12-month period, subjects were monitored for an additional six months without treatment, where it was reported that the GA lesions in the previously treated groups grew at a rate similar to sham. However, study subjects previously treated with monthly drug showed only a 12% reduction over the six-month period compared to sham, and those treated with every second month showed a 9% reduction compared to sham.
Since the announcement of the Phase II results, the sponsor has indicated that it has finalised a Phase III protocol following discussions with the FDA. The Phase III trial, scheduled to recruit its first patient in the first half of 2018, will comprise two identical 600-patient cohorts in what is described as a prospective, multicentre, randomized, double-masked, sham-injection controlled study to assess the efficacy and safety of multiple intravitreal (IVT) injections in patients with GA. The sponsor confirmed that the Phase III trials will be similar in design to the Phase II trial, including the same eligibility criteria and primary endpoint of GA lesion growth at 12 months.