Comparing Safety and Immunogenicity of HEPLISAV-B® to Engerix-B® in Chronic Kidney Disease (CKD) Patients

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the safety and immunogenicity of a new investigational hepatitis B virus vaccine, HEPLISAV-B, in patients 18 to 75 years of age who have progressive loss of kidney function.

Official Title
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An Observer-Blinded, Randomized Study Comparing the Safety and Immunogenicity of HEPLISAV-B® to Licensed Vaccine (Engerix-B®) Among Adults(18 to 75 Years of Age) With Chronic Kidney Disease (CKD)

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Biological: HEPLISAV-B
* Biological: Engerix-B
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: be 18 to 75 years of age; progressive loss of renal function as defined by glomerular filtration rate (GFR) ≤ 45 mL/min/1.73 m²; be clinically stable in the opinion of the investigator; be serum negative for HBsAg, anti-HBsAg, antibody to hepatitis B core antigen (HBcAg), Hepatitis C virus (HCV), and human immunodeficiency virus (HIV); if a woman of childbearing potential, agree to consistently use a highly effective method of birth control from screening visit through the treatment phase and for up to 28 days after the last injection; is not scheduled to undergo a kidney transplant in the next 12 months; be able and willing to provide informed consent. Exclusion Criteria: if female, is pregnant, breastfeeding, or planning a pregnancy; has a history of or is considered by the investigator to be at high risk for recent exposure to HBV, HCV, or HIV; for example, current intravenous drug use, has unprotected sex with known HBV/HIV positive partner; has known history of autoimmune disease; has previously received any HBV vaccine; has a history of sensitivity to any component of study vaccines; has current illness other than renal disease or has substance or alcohol abuse that in the opinion of the investigator would interfere with compliance or with interpretation of the study results; is undergoing chemotherapy or expected to receive chemotherapy during the study period; has a diagnosis of cancer within the last 5 years other than squamous or basal cell carcinoma of the skin; has uncontrolled diabetes or hypertension; is unwilling or unable to comply with all the requirements of the protocol; has received any blood products or immunoglobulin within 3 months prior to study entry, or likely to require infusion of blood products during the study period; has received the following prior to the first injection: 3 days: erythropoietin (exclusionary window does not apply for subjects on dialysis) 7 days: intravenous iron 21 days: any inactivated virus vaccine 28 days: any live virus vaccine systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication, with the exception of inhaled steroids granulocyte or granulocyte-macrophage colony-simulating factor (G/GM-CSF), any other investigational medicinal agent At any time: an injection of deoxyribonucleic acid plasmids or oligonucleotide

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEPLISAV-B<br>0.5 mL HEPLISAV-B and 0.5 mL Placebo | Biological: HEPLISAV-B<br>* Intramuscular (IM) injections of HEPLISAV-B at Weeks 0, 4, and 24<br>* Other names: Hepatitis B vaccine (recombinant), adjuvanted;Other: Placebo<br>* Placebo(saline) intramuscular (IM) injection at Week 8<br>* Other names: Saline;|
| Active Comparator: Engerix-B<br>2.0 mL Engerix-B | Biological: Engerix-B<br>* Intramuscular (IM) injections at Weeks 0, 4, 8, and 24<br>* Other names: Hepatitis B vaccine (recombinant);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit [mIU]/mL) after HEPLISAV-B compared to that after Engerix-B. | Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity as Measured by the Percentage of Participants With Local and Systemic Post-injection Reactions Within 7 Days After Each Injection Visit | Local reactions include redness greater than or equal to 25 mm, swelling greater than or equal to 25 mm, and pain. Systemic reactions include malaise, headache, myalgia, fatigue, and fever (temperature greater than or equal to 38ºC). This table presents post-injection reactions at active injection visits only. Post-injection reactions after the third (placebo) injection visit in the HEPLISAV-B group are not included. | 7 days after each injection visit (Weeks 0, 4, 8, and 24) | 
| Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 | SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit [mIU]/mL) after HEPLISAV-B compared to that after Engerix-B. | Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 | 
| Percentage of Participants With Anti-HBsAg Greater Than or Equal to 100 mIU/mL at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 |  | Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 | 
| Serum Anti-HBsAg Geometric Mean Concentration (GMC) at Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 |  | Weeks 4, 8, 12, 18, 24, 28, 36, 44, and 52 | 
| SPR of Participants With Type 2 Diabetes Mellitus at Week 28 | SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit [mIU]/mL) after HEPLISAV-B compared to that after Engerix-B. | Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV, chronic kidney disease, kidney failure, kidney failure,chronic, chronic kidney failure, hepatitis B virus (HBV) vaccine, hepatitis B vaccine, hepatitis B, hepatitis, prevention and control, dialysis