US-based biopharmaceutical firm Arrowhead Research has started dosing patients in a Phase IIa clinical trial of its RNAi therapeutic ARC-520, for the treatment of chronic hepatitis B virus (HBV) infection.
Sixteen chronic HBV patients will be enrolled in the trial and they will be divided into two dose cohorts with patients receiving either ARC-520 or placebo in combination with entecavir.
The multi-centre, randomised, double-blind, placebo-controlled, dose-escalation Phase IIa trial is being conducted at Queen Mary Hospital and Prince of Wales Hospital in Hong Kong.
The trial is designed to evaluate the depth and duration of hepatitis B surface antigen (HBsAg) reduction after a single intravenous dose of ARC-520 in combination with entecavir in patients with chronic HBV infection.
Patient enrolment is expected to be complete in the second quarter of this year, with top line results scheduled to be released in the third quarter.
Arrowhead president and CEO Christopher Anzalone said this is a significant milestone for the ARC-520 programme and has broad implications for the development of additional RNAi therapeutics using the Dynamic Polyconjugate, or DPC, delivery system.
"We took an important step toward clinical validation of the DPC system when the Phase 1 was completed and data indicated that ARC-520 was generally safe and well tolerated across all dose levels studied," Anzalone said.
"Our next step will be confirmation that ARC-520 induces deep and durable target gene knockdown in humans.
"We are confident that the Phase 2a will rapidly provide us with the data necessary to make that assessment as we anticipate patient enrolment and dosing may be complete in the second quarter of this year."
In the trial, single doses of ARC-520 will be assessed at up to two ascending doses of 1.0mg/kg and 2.0mg/kg.
Arrowhead said that at each of the two dose levels to be evaluated, a group of eight patients will be enrolled with six being dosed with ARC-520 and two being dosed with placebo.
The trial will be carried out in adult male and female patients aged 16 to 65 years, with immune active chronic HBV infection, HBV e antigen (HBeAg) negativity, and ongoing entecavir therapy.
The trial’s primary objective is to assess the depth and duration of HBsAg decline in response to a single dose of ARC-520 in combination with entecavir, while secondary objectives include evaluation of safety and tolerability and pharmacokinetic (PK) measures.
According to the company, additional exploratory pharmacodynamics (PD) objectives include assessment of the effect of ARC-520 on HBV DNA serum titers and antibodies to HBsAg (anti-HBs).
ARC-520 treats chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins, Arrowhead said.
Image: This electron micrograph reveals the presence of hepatitis-B virus HBV ‘Dane particles’, or virions. Photo: courtesy of Masur.