A Safety and Efficacy Study of a Single or Double Dose of HEPLISAV™ Hepatitis B Vaccine in Adults With End-Stage Renal Disease

Phase 2

Terminated

Conditions: Hepatitis B

Interventions: Biological: 1018 ISS-HBsAg-Double
Biological: 1018 ISS-HBsAg-Single

Registration Number: NCT00498212

Lead Sponsor: Dynavax Technologies Corporation

Brief Summary: The purpose of this study is to find out if a new investigational hepatitis B virus (HBV) vaccine, HEPLISAV™, is safe and effective for end-stage renal disease (ESRD) patients. Two dose levels will be studied: a single dose and a double dose. We expect both dose levels to safely immunize patients against HBV. The study will determine which dose does this best.

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. While acute HBV infection is associated with significant illness, the risk of chronic infection is of great importance since 5-10% of infected adults will not clear the infection after the initial phase of the illness. About 25% of people who do not initially clear the infection will later develop chronic active hepatitis.

This study will evaluate the safety and immunogenicity of HEPLISAV™ when administered to adults who have end-stage renal disease (glomerular filtration rate \[GFR\] ≤ 45 mL/min). Once subjects have been consented, screened, and randomized to treatment, subjects will receive a total of three injections over a 24-week period, with follow-up visits at 28 and 50 weeks. Subjects will receive 1 of the following 2 regimens:

* HEPLISAV™ single dose at Day 0, 4 weeks (1 month) and 24 weeks (6 months)

* HEPLISAV™ double dose at Day 0, 4 weeks (1 month) and 24 weeks (6 months)

Safety and tolerability will be evaluated by occurrence of adverse events, periodic laboratory tests, vital signs, and local and systemic reactogenicity.

Immunogenicity will be evaluated by the proportion of subjects exhibiting a seroprotective immune response (anti-hepatitis B surface antigen antibodies \[anti-HBsAg\] ≥ 10 milli-international unit (mIU)/mL) at Weeks 4, 12, 24, 28 and 50.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 41

Inclusion Criteria

Willing and able to give written informed consent
Have a glomerular filtration rate (GFR) ≤ 45 mL/min
Have an expectation of going on hemodialysis or are already on hemodialysis
Is serum negative for hepatitis B virus (HBV) antibodies, hepatitis C virus (HCV), and human immunodeficiency virus (HIV)
Have repeated resting blood pressure measurements ≤ 165/105 mmHg
Women of childbearing potential must be consistently using a highly effective method of birth control

Exclusion Criteria

Women who are pregnant, breastfeeding or planning a pregnancy
Any previous HBV infection
Previous vaccination (1 or more doses) with any HBV vaccine
Any previous autoimmune diseases
Have a diagnosis of chronic renal failure due to autoimmune disease
Are at high risk for recent exposure to HBV, HCV or HIV
Received any antibodies within 3 months prior to study entry
Ever received an injection with DNA plasmids or oligonucleotides
Received any vaccines within 4 weeks prior to study entry
Received any other investigational medicinal agent within 4 weeks prior to study entry

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1018 ISS-HBsAg-Double	1018 ISS-HBsAg-Double	Double dose (6000 µg 1018 ISS + 40 µg rHBsAg)
1018 ISS-HBsAg-Single	1018 ISS-HBsAg-Single	Single dose (3000 µg 1018 ISS + 20 µg rHBsAg)

Primary Outcome Measures

Name	Time	Method
Occurrence of adverse events and local and systemic reaction rates	28 weeks

Secondary Outcome Measures

Name	Time	Method
Portion of subjects who have a seroprotective immune response (anti-HBsAg ≥ 10 mIU/ml)	50 weeks

Trial Locations

Locations (3): SMBD - Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
QEII Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada
White Hills Medical Clinic
🇨🇦
St Johns, Newfoundland and Labrador, Canada