2nd year efficacy results of once-weekly administration of CTP-modified human growth hormone (MOD-4023): a phase 2 study in children with growth hormone deficiency

Abstract

Background: CTP-modified hGH (MOD-4023) has been developed for once weekly administration in GH deficient (GHD) adults and children. Immunogenicity samples of once-weekly s.c. administration of MOD-4023 were detected for the presence of binding and neutralizing anti-MOD-4023 Ab's in pediatric Phase 2 study. Objective and hypotheses: During the first year of the study, 53 pre-pubertal GHD children were treated with once-weekly s.c. injections of one of three MOD-4023 doses (42 subjects) vs. daily hGH (11 subjects). Serum samples for immunogenicity analysis were collected at pre-dose, and after 6 and 12 months of MOD-4023/hGH treatment, using the ADA and neutralizing Ab's methods for detection. Method: First, each sample was analyzed in screen format. Samples reactive for anti-MOD-4023 Ab's were confirmed for MOD-4023 in specificity format. Samples confirmed positive for anti-MOD-4023 binding Ab's, were titered and analyzed for hGH and CTP specificity format, as well as anti-MOD-4023 and anti-hGH neutralizing Ab's using cell-based assays. Results: Immunogenicity data for the first year of Phase 2 in GHD pediatric population present low titers of non-neutralized anti-MOD-4023 Abs at a similar incidence rate as Genotropin; No Ab related AE's were reported during the study. Conclusion: Qualitative methods were validated to detect whether binding as well as neutralizing Ab's were developed after once weekly administration of MOD-4023 compared to daily hGH treatment. During the first 12 months of the Phase 2 study in GHD pediatric population, along with previous Phase 2 data in GHD adults, MOD-4023 demonstrated promising immunogenicity profile, with no detection of binding Ab to the CTP moiety nor neutralizing Ab to the drug. The data affirms MOD-4023 has the potential provide promising safety outcome when injected on weekly basis.