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

Sponsor

Dynavax Technologies Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT00426712

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

10.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (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)

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Mar 1, 2008

Arms and Interventions

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™
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™
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®

Outcome Measures

Primary Outcome Measures

Occurrence of adverse events and local and systemic reaction rates [28 weeks]

Secondary Outcome Measures

Portion of subjects who have a seroprotective immune response (anti-HBsAg antibody ≥ 10 mIU/mL) [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	West Coast Clinical Trials	Costa Mesa	California	United States	92626
2	Twin Cities Clinical Research	Brooklyn Center	Minnesota	United States	55430
3	Covance	Austin	Texas	United States	78727
4	University of Virginia Health System, Nephrology Clinical Research Center	Charlottesville	Virginia	United States	22908