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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2, Single-Blind, Randomized Study of Safety and Immunogenicity Following Vaccination With Single or Double Doses of HEPLISAV™ in Adults With End-Stage Renal Disease

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: 1018 ISS-HBsAg-Single
* Biological: 1018 ISS-HBsAg-Double


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1018 ISS-HBsAg-Single<br>Single dose (3000 µg 1018 ISS + 20 µg rHBsAg) | Biological: 1018 ISS-HBsAg-Single<br>* Intramuscular (IM) injection at Day 0, Week 4 and Week 24<br>* Other names: HEPLISAV™;|
| Experimental: 1018 ISS-HBsAg-Double<br>Double dose (6000 µg 1018 ISS + 40 µg rHBsAg) | Biological: 1018 ISS-HBsAg-Double<br>* Intramuscular (IM) injection at Day 0, Week 4 and Week 24<br>* Other names: HEPLISAV™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events and local and systemic reaction rates |  | 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Portion of subjects who have a seroprotective immune response (anti-HBsAg ≥ 10 mIU/ml) |  | 50 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heplisav, Hepatitis B, Hepatitis, HBV, Hepatitis B vaccine, kidney disease, renal disease, kidney failure, renal failure