Date: 2016-07-07
Type of information: Initiation of the trial
phase: 1-2
Announcement: initiation of the trial
Company: Alnylam Pharmaceuticals (USA - MA)
Product: ALN-HBV
Action
mechanism: RNAi. ALN-HBV utilizes the company's Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate delivery platform, which enables high potency and durability with a very wide therapeutic index. Clinical results from other investigational RNAi therapeutic programs in Alnylam's pipeline that utilize ESC-GalNAc technology have demonstrated robust target gene knockdown and durability supportive of the potential for monthly, quarterly and, possibly, bi-annual subcutaneous dosing regimens, facilitating the potential for improved patient adherence. Pre-clinical study results in rodent HBV models showed that subcutaneous administration of ALN-HBV led to potent and durable knockdown of HBsAg. Single doses of ALN-HBV in mice resulted in an up to 3.6 log10 and a mean of 1.6 log10 reduction of HBsAg 15 days after a single dose. Further, multiple doses of ALN-HBV in rats showed highly durable knockdown, with effects lasting up to 4 months following three weekly doses of ALN-HBV at 3 mg/kg. In addition, ALN-HBV was generally well tolerated in 13-week GLP toxicology studies in rat and non-human primates.
Disease: Hepatitis B iInfection
Therapeutic area: Infectious diseases
Country: Australia, New Zealand, Singapore, UK
Trial
details: The Phase 1/2 trial of ALN-HBV is a randomized, single-blind, placebo-controlled study being conducted in three sequential parts. Part A is a single-dose study designed to enroll up to a total of 24 normal healthy volunteers (NHVs). Part B will be a single-dose study designed to enroll up to a total of 28 patients with chronic HBV infection. Part C will be a multi-dose study designed to enroll up to a total of 48 patients with chronic HBV infection. The primary objective of the study is to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-HBV. Secondary objectives include evaluation of pharmacokinetics and clinical antiviral activity for ALN-HBV as measured by its effects on serum HBsAg levels in hepatitis B envelope antigen (HBeAg) positive and negative chronic HBV patients (NCT02826018)
Latest
news: * On July 7, 2016, Alnylam Pharmaceuticals announced that it has initiated a Phase 1/2 clinical trial with ALN-HBV, a subcutaneously administered investigational RNAi therapeutic for the treatment of chronic hepatitis B virus (HBV) infection. The Phase 1/2 trial will be conducted initially in normal healthy volunteers, and, then, in chronic HBV patients. Initiation of this trial is based on encouraging pre-clinical data presented at the American Association for the Study of Liver Disease annual meeting in November 2015 . The Company expects to report initial clinical data from patients in this study in mid-2017.
