hATTR is a progressive, life-threatening disease caused by pathogenic TTR protein in organs. ALN-TTRsc02 is an investigational GalNAc-conjugated siRNA designed to inhibit synthesis of mutant and wild-type TTR protein.
The primary objective is to evaluate the safety and tolerability of ALN-TTRsc02. Secondary objectives include the assessment of the pharmacodynamic effect and characterization of the pharmacokinetics of ALN-TTRsc02.
Patients and methods
Phase 1, multi-center, randomized, ascending fixed-dose study of ALN-TTRsc02 in up to 110 healthy volunteers. Study included cohorts of eight participants randomized 6:2 to receive a single dose of subcutaneously administered ALN-TTRsc02 or placebo.
Between June 2016 and October 2017, 80 healthy volunteers (60 ALN-TTRsc02 and 20 Placebo) have been randomized and treated in 5, 25, 50, 100, 200 and 300mg cohorts. ALN-TTRsc02 has been well tolerated at all dose levels and no serious adverse events have been observed. Based on preliminary data, ALN-TTRsc02 demonstrates robust TTR reduction that is maintained over an extended period of time.
Based on preliminary data, ALN-TTRsc02 demonstrates TTR reduction that is maintained over an extended period of time.
Both sustained TTR reduction at clinically relevant doses observed on study to date and modeling data suggests that quarterly or bi-annual dosing with ALN-TTRsc02 will be supported targeting hepatic TTR production.Le texte complet de cet article est disponible en PDF.
Mots clés : Administration sous-cutanée, ALN-TTRsc02, HTTR