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

Phase 1
Completed
Conditions
Hepatitis B
Interventions
Biological: Hepatitis B Vaccine (Recombinant)
Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen
Registration Number
NCT00426712
Lead Sponsor
Dynavax Technologies Corporation
Brief Summary

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.

Detailed Description

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®.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
4Hepatitis B Vaccine (Recombinant)-
11018 ISS immunostimulatory oligonucleotide with HBV surface antigenLow dose
21018 ISS immunostimulatory oligonucleotide with HBV surface antigenMiddle dose
31018 ISS immunostimulatory oligonucleotide with HBV surface antigenHigh dose
Primary Outcome Measures
NameTimeMethod
Occurrence of adverse events and local and systemic reaction rates28 weeks
Secondary Outcome Measures
NameTimeMethod
Portion of subjects who have a seroprotective immune response (anti-HBsAg antibody ≥ 10 mIU/mL)28 days

Trial Locations

Locations (4)

University of Virginia Health System, Nephrology Clinical Research Center

🇺🇸

Charlottesville, Virginia, United States

West Coast Clinical Trials

🇺🇸

Costa Mesa, California, United States

Covance

🇺🇸

Austin, Texas, United States

Twin Cities Clinical Research

🇺🇸

Brooklyn Center, Minnesota, United States

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