Safety of HEPLISAV™ Hepatitis B Virus Vaccine in End-stage Kidney Failure Patients

A Phase 1, Randomized, Observer-blind, Dose-escalating Study in Adult End-stage Renal Failure Patients to Explore the Safety, Tolerability, Pharmacokinetics and Immune Response to Recombinant Hepatitis B Virus Surface Antigen (rHBsAg) Co-administered With Dynavax Immunostimulatory Phosphorothioate Oligodeoxyribonucleotide (1018 ISS)

The purpose of this study is to find out if a new investigational hepatitis B virus vaccine, HEPLISAV™, is safe in patients at least 40 years of age who have progressive loss of kidney function with more advanced stage 3 (GFR ≤ 45 mL/min) or stage 4 chronic kidney disease, and are expected to eventually go on hemodialysis.

Infection with hepatitis B virus (HBV) is a major global health problem. Worldwide, it is estimated that 2 billion people have been infected previously and 350 million are chronically infected. About 25% of people who do not initially clear the infection will later develop chronic active hepatitis. Hemodialysis and pre-dialysis patients with kidney failure have multiple immune defects that make them more likely to develop a chronic infection. In addition, hemodialysis increases the risk of exposure to HBV. Existing HBV vaccines are effective in preventing infection in healthy adults. However, poor responses occur in people who are over 40 years of age and have end-stage kidney failure.

This study will evaluate the safety, tolerability and immune response of three escalating dose levels of HEPLISAV™, compared with a commercially available HBV vaccine, Engerix-B®, in patients at least 40 years of age who have progressive loss of kidney function with more advanced stage 3 (GFR ≤ 45 mL/min) or stage 4 chronic kidney disease and are expected to eventually go on hemodialysis. About 72 patients will be included in the study. Once patients have been consented, screened, and randomized to treatment, they will receive four injections over a 24-week period, with follow-up visits at 28 and 50 weeks. Safety and tolerability will be evaluated by occurrence of adverse events, periodic laboratory tests, vital signs, and local/systemic reactogenicity.

Comparison: Patients will receive treatment with one of three escalating dose levels of HEPLISAV™ or the comparator vaccine, Engerix-B®.

Inclusion Criteria:

• Willing and able to give written informed consent
• Progressive loss of kidney function with more advanced stage 3 (GFR at least 45 mL/min) or stage 4 chronic kidney disease by National Kidney Foundation classification, and are expected to eventually go on hemodialysis
• Body mass index of 31 or less

Exclusion Criteria:

• Received previous vaccination with any HBV vaccine (1 or more doses)
• Any history of HBV infection
• Pregnant or breast-feeding, or planning a pregnancy during the study
• Has autoimmune disease
• Diagnosis of chronic kidney failure due to autoimmune disease
• Receiving hemodialysis treatment at the time of enrollment
• Received any blood products or antibodies within 3 months prior to study entry, or is likely to require blood products during the study
• Ever received an injection with DNA plasmids or oligonucleotides
• Received erythropoietin within 7 days prior to the first study injection
• Received vaccination with any vaccines during the 4 weeks prior to study entry
• Received any other investigational medicinal agent during the 4 weeks prior to study entry