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John I Wurzelmann, Francisco J Lopez, Mike Fries, Shawn Patrick Shearn, Michael R Schwartz, Astrid Yeo, Lingkang Huang, Amitha Domalpally, Ronald P Danis, Rabia Ozden, BAM114341; SNPs Associated with Complement Factor I Do Not Predict 4-month Lesion Growth Rate in Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2850.
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BAM114341 is a GSK-sponsored, randomized, double masked, placebo-controlled phase II study to investigate the safety and efficacy of a monoclonal antibody directed against β-amyloid in patients with Geographic Atrophy (GA). Understanding determinants of GA growth rates will help patients, clinicians and researchers by informing prognosis, treatment options and future study designs. The MAHALO study reported that a subgroup carrying the risk allele for SNP rs17440077 near the Complement Factor I (CFI) locus was associated with rapid growth of GA . We sought to evaluate the effect of genetic variants near the CFI locus on GA growth rate (GR).
BAM114341 includes a 4 month observation period prior to randomization. Baseline GRs were measured by color fundus photography (CP) and fundus autofluorescence (FAF). These rates are to be used for later comparison with post-intervention rates. Subjects were required to have GA of total area 1.9-17 mm2. Blood for genetic analysis was drawn at study entry. Genetic variants rs4698775 and rs17440077 near CFI were genotyped using TaqMan® Assays. Predictors of GR were identified by mixed models repeated measures regression which included baseline lesion size, period of observation, genotype and interaction terms as covariates. Models considering GA measured by CP and FAF were considered separately.
191 subjects completed the 4 month observation period. The average age of participants was 77.2 years (SD 8.6), and average baseline lesion size by CP was 7.7 mm2 (SD 4.6). Average GR at baseline (~ 4 months after screening) was 2.16 mm2/year. Genetic data were available for 170 subjects. All models contained terms for baseline lesion size and time of observation and these were consistently significant predictors of GR. In no model was either SNP a statistically significant predictor of GR. This was true for both CP and FAF based models.
SNPs associated with the CFI locus did not predict GR during a 4 month observation period. The MAHALO association between carriage of the rs17440077 risk allele and rapid GA growth was not observed in this study. The different results from the two studies may be attributed to differences in methodology, in the populations under study or due to the short observation period of the current study. Repeat analyses as the study progresses may support a relationship as statistical power increases.
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