Safety of HEPLISAV™ Hepatitis B Virus Vaccine in End-Stage Kidney Failure Patients - Full Text View

Sponsored by:	Dynavax Technologies Corporation
Information provided by:	Dynavax Technologies Corporation
ClinicalTrials.gov Identifier:	NCT00426712

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 I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Single Blind (Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety Study
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:

MedlinePlus related topics: Hepatitis Hepatitis B Kidney Failure

Drug Information available for: Hepatitis B Vaccines

U.S. FDA Resources

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
Estimated Study Completion Date:	April 2008
Estimated Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Low dose	Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen IM (in the muscle) injections on Day 0, Week 4 and Week 24, plus a placebo (salt solution) injection at Week 8
2: Experimental Middle dose	Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen IM (in the muscle) injections on Day 0, Week 4 and Week 24, plus a placebo (salt solution) injection at Week 8
3: Experimental High dose	Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen IM (in the muscle) injections on Day 0, Week 4 and Week 24, plus a placebo (salt solution) injection at Week 8
4: Active Comparator	Biological: Hepatitis B Vaccine (Recombinant) IM (in the muscle) injections on Day 0, Week 4, Week 8 and Week 24

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

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:

Dynavax Webpage This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Dynavax Technologies Corporation ( Eduardo Martins, MD, DPhil / Vice President, Clinical Development )
Study ID Numbers:	DV2-HBV-09
Study First Received:	January 23, 2007
Last Updated:	January 22, 2008
ClinicalTrials.gov Identifier:	NCT00426712 History of Changes
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

Study placed in the following topic categories:

Liver Diseases
Renal Insufficiency
Kidney Failure, Chronic
Hepatitis, Viral, Human
Hepatitis
Virus Diseases
Digestive System Diseases

Urologic Diseases
Renal Insufficiency, Chronic
Hepatitis B
DNA Virus Infections
Kidney Diseases
Kidney Failure

Additional relevant MeSH terms:

Virus Diseases
Hepatitis
Renal Insufficiency
Liver Diseases
Digestive System Diseases
Urologic Diseases

Hepatitis B
Hepatitis, Viral, Human
DNA Virus Infections
Kidney Diseases
Hepadnaviridae Infections
Kidney Failure

ClinicalTrials.gov processed this record on July 06, 2009