Pharmacodynamic Study of Miransertib in Individuals with Proteus Syndrome.

ABSTRACT: Proteus syndrome is a life-threatening segmental overgrowth syndrome caused by a mosaic gain-of-function AKT1 variant. There are no effective treatments for Proteus syndrome. Miransertib is an AKT1 inhibitor that, prior to this study, has been evaluated only in adult oncology trials. We designed a non-randomized, phase 0/1 pilot study of miransertib in adults and children with Proteus syndrome to identify an appropriate dosage starting point for a future efficacy trial using a pharmacodynamic endpoint. The primary endpoint was a 50% reduction in the tissue levels of AKT phosphorylation from biopsies in affected individuals. We also evaluated secondary efficacy endpoints. We found that a dose of 5 mg/m²/day (1/7 the typical dose used in oncology) led to a 50% reduction in phospho

SUBMITTER: Keppler-Noreuil KM 

PROVIDER: S-EPMC6407523 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature