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

March 18, 2019 updated by: Dynavax Technologies Corporation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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®.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Costa Mesa, California, United States, 92626
        • West Coast Clinical Trials
    • Minnesota
      • Brooklyn Center, Minnesota, United States, 55430
        • Twin Cities Clinical Research
    • Texas
      • Austin, Texas, United States, 78727
        • Covance
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System, Nephrology Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Low dose
Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen
Intramuscular (IM) injections on Day 0, Week 4 and Week 24, plus a placebo (salt solution) injection at Week 8
Other Names:
  • HEPLISAV™
Active Comparator: 4
Biological: Hepatitis B Vaccine (Recombinant)
IM (in the muscle) injections on Day 0, Week 4, Week 8 and Week 24
Other Names:
  • ENGERIX-B®
Experimental: 2
Middle dose
Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen
Intramuscular (IM) injections on Day 0, Week 4 and Week 24, plus a placebo (salt solution) injection at Week 8
Other Names:
  • HEPLISAV™
Experimental: 3
High dose
Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen
Intramuscular (IM) injections on Day 0, Week 4 and Week 24, plus a placebo (salt solution) injection at Week 8
Other Names:
  • HEPLISAV™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Occurrence of adverse events and local and systemic reaction rates
Time Frame: 28 weeks
28 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Portion of subjects who have a seroprotective immune response (anti-HBsAg antibody ≥ 10 mIU/mL)
Time Frame: 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dynavax Technologies Corporation

Investigators

  • Study Director: Eduardo Martins, MD, DPhil, Dynavax Technologies Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

January 23, 2007

First Submitted That Met QC Criteria

January 24, 2007

First Posted (Estimate)

January 25, 2007

Study Record Updates

Last Update Posted (Actual)

March 20, 2019

Last Update Submitted That Met QC Criteria

March 18, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DV2-HBV-09

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

3/2017 No change to status of this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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