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

Phase 3CompletedNCT04193189

National Institute of Allergy and Infectious Diseases (NIAID)638 enrolled

Overview

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

This phase III/IV study evaluated the response to and safety of the HBV vaccine HEPLISAV-B in two study populations of people living with HIV: prior HBV vaccine recipients who are deemed non-responders (Group A) and individuals who are naïve to HBV vaccination (Group B). The analyses were conducted as separate evaluations of the two study populations for all primary and secondary objectives. Group A (HBV vaccine non-responders) The study was designed as an open-label three-arm study to evaluate whether: 1. HEPLISAV-B vaccination given as a two-dose series achieves non-inferior seroprotection response (SPR) compared to standard dose ENGERIX-B. 2. HEPLISAV-B vaccination given as a three-dose series achieves superior SPR compared to standard dose ENGERIX-B. Participants were 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): 2-CpG: Two doses of HEPLISAV-B at weeks 0 and 4. 3-CpG: Three doses of HEPLISAV-B at weeks 0, 4, and 24. 3-alum: Three doses of ENGERIX-B at weeks 0, 4, and 24. The target sample size in Group A was 561 participants, 187 participants in each arm. Group B (Naïve to HBV vaccination) Group B study was a single arm evaluation of vaccine response and safety of three doses of HEPLISAV-B. The target sample size was 73 participants. In both groups, participants were scheduled to attend several study visits through Week 72. All participants were to remain on their antiretroviral therapy (ART), not provided by the study, throughout the study. Visits included physical examinations and blood collection. For 7 days after each vaccination, participants were asked to record temperature and any reactions they experienced.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

638

Conditions

HIV Infection Hepatitis B

Interventions

HEPLISAV-BBIOLOGICAL

Administered by IM injection

ENGERIX-BBIOLOGICAL

Administered by IM injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (41)

Outcomes

Primary Outcomes

Percentage of Participants With Primary Seroprotection Response

Primary seroprotection response was defined as antibody titer against hepatitis B surface antigen (anti-HBs) ≥10 mIU/mL at 8 weeks after 2-dose vaccination series and at 4 weeks after 3-dose vaccination series. If the completion of the vaccine series was delayed (a delay of ≤4 weeks was allowed), the trial protocol specified obtaining an antibody result at 8 weeks for the 2-dose series or at 4 weeks for the 3-dose series after vaccine completion for use in the primary outcome analysis. The study was designed separately for the two study populations (Groups A and B), and the analysis was conducted separately, as prespecified in the study protocol and Statistical Analysis Plan (SAP). In Group A, two-sided 97.5% confidence intervals (CI) were specified for the SPR differences between study arms (presented in the Statistical Analyses sections below). In Group B, two-sided 95% Wilson CI around the single-arm estimate was specified (presented in the Data Table below).

Time frame: Week 12 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and in Group B

Percentage of Participants With Adverse Events (AEs)

The protocol required reporting of (1) Grade ≥2 AEs, (2) AEs that led to a change in study treatment regardless of grade, (3) AEs meeting serious AE (SAE) definition or expedited AE (EAE) reporting requirement, (4) Grade ≥1 local and systemic injection reactions within 7 days of any study vaccine injection, (5) medically attended adverse events (MAAE) regardless of grade, and (6) potential immune-mediated AEs regardless of grade. Grading was per DAIDS AE Grading Table (Version 2.1): Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening) and 5 (death). DAIDS EAE Manual (V1.0) was used. Wilson method was used for confidence intervals.

Time frame: From study entry to study discontinuation (Week 72 or premature discontinuation)

Secondary Outcomes

Percentage of Participants With Seroprotection Response

Seroprotection response (SPR) was defined as antibody titer against hepatitis B surface antigen (anti-HBs) ≥10 mIU/mL. Study visit weeks are according to protocol-specified visit windows; anti-HBs results outside visit windows were not included. These are snapshots at scheduled visits irrespective of delayed vaccinations, unlike the visits defined in Primary Outcome 1. The study was designed separately for the two study populations (Groups A and B), and the analysis was conducted separately, as prespecified in the study protocol and Statistical Analysis Plan (SAP). In Group A, two-sided 97.5% confidence intervals (CI) were specified for the SPR differences between study arms (presented in the Statistical Analyses sections below). In Group B, two-sided 95% Wilson CIs around the single-arm estimates were specified (presented in the Data Table below).

Data from ClinicalTrials.gov

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