Phase 1 study of ALN-TTRsc02, a subcutaneously administered investigational RNAi therapeutic for the treatment of transthyretin-mediated amyloidosis - 27/03/19
Résumé |
Introduction |
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.
Objectives |
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.
Results |
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.
Discussion |
Based on preliminary data, ALN-TTRsc02 demonstrates TTR reduction that is maintained over an extended period of time.
Conclusion |
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
Plan
Vol 175 - N° S1
P. S129 - avril 2019 Retour au numéro
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