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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dynavax Technologies Corporation
ClinicalTrials.gov Identifier:
NCT00426712
First received: January 23, 2007
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis B
Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen
Biological: Hepatitis B Vaccine (Recombinant)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Dynavax Technologies Corporation:

Primary Outcome Measures:
  • Occurrence of adverse events and local and systemic reaction rates [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Portion of subjects who have a seroprotective immune response (anti-HBsAg antibody ≥ 10 mIU/mL) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: January 2006
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: HEPLISAV™
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 Name: 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 Name: 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 Name: ENGERIX-B®

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®.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00426712

Locations
United States, California
West Coast Clinical Trials
Costa Mesa, California, United States, 92626
United States, Minnesota
Twin Cities Clinical Research
Brooklyn Center, Minnesota, United States, 55430
United States, Texas
Covance
Austin, Texas, United States, 78727
United States, Virginia
University of Virginia Health System, Nephrology Clinical Research Center
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Dynavax Technologies Corporation
Investigators
Study Director: Eduardo Martins, MD, DPhil Dynavax Technologies Corporation
  More Information

Additional Information:
No publications provided

Responsible Party: Dynavax Technologies Corporation
ClinicalTrials.gov Identifier: NCT00426712     History of Changes
Other Study ID Numbers: DV2-HBV-09
Study First Received: January 23, 2007
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dynavax Technologies Corporation:
Chronic kidney failure
Chronic kidney disease
Hemodialysis
HBV vaccine
Hepatitis B vaccine
Hepatitis B
Hepatitis
HBV
Prevention & Control

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014