B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B
- Conditions
- HIV InfectionHepatitis B
- Interventions
- Registration Number
- NCT04193189
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 638
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A, 2-CpG: HEPLISAV-B (two injections) HEPLISAV-B Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular (IM) injection at Weeks 0 and 4. Group A, 3-CpG: HEPLISAV-B (three injections) HEPLISAV-B Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by IM injection at Weeks 0, 4, and 24. Group A, 3-alum: ENGERIX-B (three injections) ENGERIX-B Participants were prescribed 1 mL of ENGERIX-B (conventional hepatitis B vaccine with an aluminum hydroxide adjuvant) by IM injection at Weeks 0, 4, and 24. Group B: HEPLISAV-B (three injections) HEPLISAV-B Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by IM injection at Weeks 0, 4, and 24.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Primary Seroprotection Response Week 12 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and in Group B 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).
Percentage of Participants With Adverse Events (AEs) From study entry to study discontinuation (Week 72 or premature discontinuation) 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Seroprotection Response Weeks 4, 8, 12, 24, 28, 32 (Group A 3-CpG and 3-alum and Group B), 48 (Group A 3-CpG and 3-alum and Group B), 52 (Group A 2-CpG) and 72. The visit schedule differed between the study arms. 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).
Count of Participants by Anti-HBs Titer Categories Weeks 4, 8, 12, 24, 28, 32 (Group A 3-CpG and 3-alum and Group B), 48 (Group A 3-CpG and 3-alum and Group B), 52 (Group A 2-CpG) and 72. The visit schedule differed between the study arms. Count of participants by antibody titer against hepatitis B surface antigen (anti-HBs), categorized using cutoffs at 5, 10, 100 and 1000 mIU/mL. The testing assay lower limit of quantitation was 5 mIU/mL and upper limit 1000 mIU/mL. Study visit weeks are according to protocol-specified visit windows; anti-HBs results outside visit windows were not included. Because high proportions of participants achieved anti-HBs above the assay upper limit of quantitation, the planned geometric mean analysis was not conducted. Instead, anti-HBs were summarized according to the categories shown in the Data Table below.
Percentage of Participants With Grade ≥2 AEs Post-vaccination Adverse Events From study vaccination initiation to 4 weeks after last study vaccination (Week 8 in Group A 2-CpG, Week 28 in Group A 3-CpG and 3-alum and Group B) 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. This outcome is limited to the Grade ≥2 AEs that occurred within 4 weeks after any study vaccination. 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.
Trial Locations
- Locations (41)
Vanderbilt Therapeutics (VT) CRS
🇺🇸Nashville, Tennessee, United States
De La Salle Health Science Institute Angelo King Medical Research Center
🇵🇭Silang, Philippines
Alabama CRS
🇺🇸Birmingham, Alabama, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
UCSD Antiviral Research Center
🇺🇸San Diego, California, United States
Ucsf Hiv/Aids Crs
🇺🇸San Francisco, California, United States
Harbor-UCLA CRS
🇺🇸Torrance, California, United States
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
Whitman-Walker Health CRS
🇺🇸Washington, District of Columbia, United States
The Ponce de Leon Center CRS
🇺🇸Atlanta, Georgia, United States
Scroll for more (31 remaining)Vanderbilt Therapeutics (VT) CRS🇺🇸Nashville, Tennessee, United States