JAMA Ophthalmology, June 2018
A phase 2 trial of lampalizumab for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) suggested that this investigational compound might reduce the rate of GA enlargement. This result led to a pair of phase 3 trials, in which Holz et al. compared outcomes for intravitreal lampalizumab and a sham procedure. In the phase 3 trials, however, lampalizumab did not appear to slow lesion progression, nor was there a link between faster GA progression and presence of the complement factor I (CFI) biomarker.
The phase 3 trials, known as Chroma and Spectri, were double-masked, randomized, sham-controlled studies of identical design. Enrollees were at least 50 years old and had bilateral GA without previous or active choroidal neovascularization in either eye. Altogether, 275 sites participated, representing 23 countries. At baseline, GA lesions measured 2.54 mm2 to 17.78 mm2 and displayed banded or diffuse fundus autofluorescence patterns.
Participants were randomized (2:1:2:1) to receive 1 of the following regimens: 10-mg intravitreal injection of lampalizumab every 4 weeks, sham procedure every 4 weeks, 10-mg injection of lampalizumab every 6 weeks, or sham procedure every 6 weeks. Efficacy was assessed by calculating mean changes in GA lesion area from baseline to week 48, determined from centrally read fundus autofluorescence images and by the presence or absence of the CFI biomarker. The Chroma study included 906 patients (553 women; mean age, 78.1 years), and Spectri included 975 patients (578 women; mean age, 77.9 years). Overall, 1,732 (92%) of the combined study population completed treatment through week 48.
Adjusted mean increases in GA lesion area ranged from 1.93 mm2 to 2.09 mm2 across study groups. Differences in adjusted mean change in GA area (lampalizumab minus sham) for lampalizumab at 4-week intervals were –0.02 mm2 (p = .80) in Chroma and 0.16 mm2 (p = .048) in Spectri. The corresponding differences in lesion area for lampalizumab at 6-week intervals were 0.05 mm2 and 0.09 mm2. No benefit of lampalizumab was observed among prespecified subgroups, including CFI subsets. Through week 48, endophthalmitis occurred after 5 of 12,447 injections (0.04%); all 5 occurred in participants receiving active treatment. Approximately 3% of subjects who received lampalizumab experienced intraocular pressure increases that were considered serious.
To date, these are the largest randomized clinical trial studies of GA secondary to AMD. These results highlight the rapid substantial loss of retinal tissue and the risk of vision decline in patients with GA. Further analyses of the study data may provide new insights into the pathophysiology of AMD, which may guide the design of future trials.
The original article can be found here.