B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B

Study Overview
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Brief Summary
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The purpose of this study is to evaluate response to and safety of the HBV vaccine HEPLISAV-B in two study populations living with HIV: prior HBV vaccine recipients who are deemed non-responders and individuals who are naïve to HBV vaccination.

Detailed Description
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This phase III/IV study will evaluate the response to and safety of the HBV vaccine HEPLISAV-B in two study populations living with HIV: prior HBV vaccine recipients who are deemed non-responders (Group A) and individuals who are naïve to HBV vaccination (Group B). Group A (HBV vaccine non-responders) The study is designed as an open-label three-arm study to evaluate whether: HEPLISAV-B vaccination given as a two-dose series achieves non-inferior seroprotection response (SPR) compared to standard dose ENGERIX-B. HEPLISAV-B vaccination given as a three-dose series achieves superior SPR proportion compared to standard dose ENGERIX-B. Participants are randomized in 1:1:1 ratio to the following study arms, stratified by sex at birth (male vs. female) and diabetes diagnosis status (yes vs. no): Arm 1: Two doses of HEPLISAV-B at weeks 0 and 4. Arm 2: Three doses of HEPLISAV-B at weeks 0, 4, and 24. Arm 3: Three doses of ENGERIX-B at weeks 0, 4, and 24. The target sample size in Group A is 561 participants, 187 participants in each arm. Group B (Naïve to HBV vaccination) Group B study is a single arm evaluation of vaccine response and safety of three doses of HEPLISAV-B. The target sample size is 73 participants. All participants will remain on their non-study-provided antiretroviral therapy (ART) throughout the study. Participants in both groups will attend several study visits through Week 72. Visits may include physical examinations and blood collection. For 7 days after each vaccination, participants will record temperature and any reactions they have to the vaccine.

Official Title
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B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B

Conditions
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HIV Infection, Hepatitis B

Intervention / Treatment
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* Biological: HEPLISAV-B
* Biological: ENGERIX-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria, Groups A and B HIV-1 infection On current HIV-1 antiretroviral therapy (ART) CD4+ T-cell count ≥100 cells/mm^3 HIV-1 RNA <1000 copies/mL Inclusion Criteria, Group A only Serum Hepatitis B antibody <10 mlU/mL, non-reactive (negative), or indeterminate Documentation of HBV vaccination >168 days prior to study entry Inclusion Criterion, Group B only Serum Hepatitis B antibody non-reactive (negative) within 45 days prior to study entry Exclusion Criteria, Groups A and B Infection or prior exposure to HBV Serum HBsAb level ≥10 mlU/mL or positive at screening or any other time prior to screening Presence of any active or acute AIDS-defining opportunistic infections Solid organ transplantation History of ascites, encephalopathy, or variceal hemorrhage Diagnosis of chronic kidney disease (CKD) stage G4 Cancer diagnosis within 5 years Currently receiving chemotherapy Chronic use and/or receipt of systemically administered immunosuppressive Known allergy/sensitivity or any hypersensitivity to any HBV vaccine or yeast Active, serious infection other than HIV-1 Receipt of any inactivated virus vaccine within 14 days Receipt of any of the following within 45 days prior to study entry: Live virus vaccine Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) Any other investigational medicinal agent Receipt of immunoglobulin or blood products within 90 days prior to study entry Receipt of an injection of DNA plasmids or oligonucleotides within 60 days prior to study entry Exclusion Criteria, Group A only Hepatitis B virus vaccination ≤168 days prior to study entry Receipt of HEPLISAV-B vaccine at any time prior to study entry Exclusion Criterion, Group B only Known HBV vaccination prior to study entry

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A, Arm 1: HEPLISAV-B (two injections)<br>Participants will receive 0.5 mL of HEPLISAV-B by intramuscular (IM) injection at Weeks 0 and 4. | Biological: HEPLISAV-B<br>* Administered by IM injection<br>|
| Experimental: Group A, Arm 2: HEPLISAV-B (three injections)<br>Participants will receive 0.5 mL of HEPLISAV-B by IM injection at Weeks 0, 4, and 24. | Biological: HEPLISAV-B<br>* Administered by IM injection<br>|
| Experimental: Group A, Arm 3: ENGERIX-B (three injections)<br>Participants will receive 1 mL of ENGERIX-B by IM injection at Weeks 0, 4, and 24. | Biological: ENGERIX-B<br>* Administered by IM injection<br>|
| Experimental: Group B: HEPLISAV-B (three injections)<br>Participants will receive 0.5 mL of HEPLISAV-B by IM injection at Weeks 0, 4, and 24. | Biological: HEPLISAV-B<br>* Administered by IM injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection response defined as hepatitis B virus surface antibody (HBsAb) ≥10 mIU/mL |  | Week 12 in Group A, Arm 1, Week 28 in Group A, Arms 2 and 3 and in Group B | 
| Occurrence of Adverse events (AEs) | DAIDS AE Grading Table (Version 2.1) will be used. | From vaccination initiation to study discontinuation (Week 72 or premature discontinuation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection response defined as HBsAb ≥10 mIU/mL |  | Weeks 4, 8, 12, 24, 28, 32, 48, 52 and 72 | 
| HBsAb titer |  | Weeks 4, 8, 12, 24, 28, 32, 48, 52 and 72 | 
| Occurrence of Grade ≥2 AEs within 4 weeks after each injection |  | From vaccination initiation to Week 28 |