Back to resultsTLR-9 Adjuvanted Vaccination for Chronic Hepatitis B (BOOST-9)
Primary Purpose
Hepatitis B
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hepatitis B Vaccine Recombinant, Adjuvanted Intramuscular Solution [HEPLISAV-B]
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B focused on measuring hepatitis B, Toll-like receptor, vaccine, hepatitis B surface antibody, HBsAb, anti-HBsAg, hepatitis B surface antigen, HBsAg, TLR9, CpG
Eligibility Criteria
Inclusion Criteria:
In order to participate in this study, an individual must meet all the following criteria:
- >18 years old
- Diagnosed with CHB infection, without HIV, hepatitis C nor hepatitis D co-infections
- Currently receiving OAV with HBV VL <100 IU/ml for ≥ 12 months
- Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, and other study procedures.
- Determined by medical history, targeted physical examination, and clinical judgement of the investigator to be in good health.
CHB infection is defined as any individual with documentation of the following in the past:
• Positive HBsAg and/or detectable HBV DNA test
Exclusion Criteria:
A participant will be ineligible to participate on this study if any of the following criteria are met:
- Pregnancy or breast feeding.
- Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥ 20 mg/day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to Day 1.
- Received or plans to receive live virus vaccines within 4 weeks, and inactivated vaccine within 2 weeks prior to randomization; or plans to receive a non-study vaccine within 28 days after any dose of study vaccine (with exception for seasonal influenza vaccine within 14 days of study vaccine).
- Administration of any blood products within 3 months prior to randomization.
- Participation in a study with an investigational study product or device within 30 days of randomization.
- Has allergies to any hepatitis B and/or yeast-based vaccines.
Subjects meeting any of the following laboratory parameters at screening:
- ALT greater than 3 times the upper limit of normal
- Elevated total bilirubin WITH direct bilirubin greater than 2 times upper limit of normal
- Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as ≥ 38.0°C/100.4°F). Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
- Have any chronic or acute or unstable conditions that the investigator considers a contraindication to study participation.
Sites / Locations
- Institute of Human Virology, University of Maryland School of Medicine
- Dr Sang V Tran Internal Medicine Practice
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Intervention - vaccination
No vaccination
Arm Description
HEPLISAV-B is available in pre-filled, single-dose 0.5 mL vials. Each dose contains 20 μg of HBsAg and 3,000 μg of 1018 adjuvant. HEPLISAV-B is administered as an intramuscular injection in the deltoid region. Study subjects randomized to the vaccine group will receive a total of 2 injections, each administered at least 4 weeks apart - the same dosing schedule recommended for hepatitis B prevention. Once enrolled, participants will have study visits on days 0 (first injection), 14, 28, 56, and 196 with phone call follow ups on days 7, 35, and 393. Research blood samples will be collected at days 0, 14, 28, 56, 196.
Participants randomized to the control group will have study visits on days 0, 14, 28, 56, and 196 with phone call follow ups on days 7, 35, and 393. Research blood samples will be collected at days 0, 14, 28, 56, 196.
Outcomes
Primary Outcome Measures
Safety and reactogenicity of the Hepatitis B Virus Surface Antigen, Recombinant (HEPLISAV-B; Dynavax Technologies Corporation) Vaccine in patients with chronic hepatitis B
Occurrence of local and systemic solicited adverse events
Occurrence of unsolicited adverse events
Unsolicited adverse events
Medically Attended Adverse Events
Occurrence of Medically Attended Adverse Events (MAAEs)
Secondary Outcome Measures
Full Information
NCT ID
NCT04843852
First Posted
April 6, 2021
Last Updated
July 19, 2022
Sponsor
University of Maryland, Baltimore
1. Study Identification
Unique Protocol Identification Number
NCT04843852
Brief Title
TLR-9 Adjuvanted Vaccination for Chronic Hepatitis B
Acronym
BOOST-9
Official Title
Augmentation of Humoral Immunity Using Toll-Like Receptor (TLR) 9 Adjuvanted HBV Surface Antigen to Enhance Anti-HBSAg Response
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Study not implemented
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Unmethylated cystine-guanosine dinucleotide (CpG) motifs are pathogen-associated molecular patterns (PAMPs) associated with bacterial and viral-derived DNA that activate the innate and humoral immunity via toll-like receptor 9. This is a randomized controlled pilot study evaluating the clinical and immune correlates of a seroprotective immune response against a CpG-adjuvanted vaccine for hepatitis B.
Detailed Description
This is an open-label, randomized, pilot study to assess the effect of CpG-adjuvanted vaccination among people with chronic hepatitis B. This study will evaluate the effect of CpG-adjuvanted vaccination on B-cells that produce anti-HBsAg antibody.
The primary hypothesis is that TLR9 agonism with CpG-adjuvanted hepatitis B vaccine will increase the number of anti-HBsAg producing B-cells in people with chronic hepatitis B infection who are virally suppressed on nucleos(t)ide analogue (NUC) therapy.
In this study, 40 people with chronic hepatitis B virally suppressed on NUC therapy will be randomized in a 1:1 fashion to receive an 0.5ml intramuscular injection of HEPLISAV-B vaccine - an FDA approved vaccine for preventing hepatitis B infection. Participants randomized to receive the vaccine will receive a total of 2 injections, at day 0 and week 4. Participants will be evaluated at days 7, 14, 28, 35, 56, 96, 393 for adverse events, with and blood sample collections on days 0, 14, 28, 56, 196.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
hepatitis B, Toll-like receptor, vaccine, hepatitis B surface antibody, HBsAb, anti-HBsAg, hepatitis B surface antigen, HBsAg, TLR9, CpG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Randomized clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intervention - vaccination
Arm Type
Experimental
Arm Description
HEPLISAV-B is available in pre-filled, single-dose 0.5 mL vials. Each dose contains 20 μg of HBsAg and 3,000 μg of 1018 adjuvant. HEPLISAV-B is administered as an intramuscular injection in the deltoid region.
Study subjects randomized to the vaccine group will receive a total of 2 injections, each administered at least 4 weeks apart - the same dosing schedule recommended for hepatitis B prevention.
Once enrolled, participants will have study visits on days 0 (first injection), 14, 28, 56, and 196 with phone call follow ups on days 7, 35, and 393. Research blood samples will be collected at days 0, 14, 28, 56, 196.
Arm Title
No vaccination
Arm Type
No Intervention
Arm Description
Participants randomized to the control group will have study visits on days 0, 14, 28, 56, and 196 with phone call follow ups on days 7, 35, and 393. Research blood samples will be collected at days 0, 14, 28, 56, 196.
Intervention Type
Drug
Intervention Name(s)
Hepatitis B Vaccine Recombinant, Adjuvanted Intramuscular Solution [HEPLISAV-B]
Intervention Description
one 0.5ml intramuscular injection on day 0 and week 4.
Primary Outcome Measure Information:
Title
Safety and reactogenicity of the Hepatitis B Virus Surface Antigen, Recombinant (HEPLISAV-B; Dynavax Technologies Corporation) Vaccine in patients with chronic hepatitis B
Description
Occurrence of local and systemic solicited adverse events
Time Frame
Baseline to 7 days following each vaccine dose
Title
Occurrence of unsolicited adverse events
Description
Unsolicited adverse events
Time Frame
from dose 1 to 28 days following each vaccine dose
Title
Medically Attended Adverse Events
Description
Occurrence of Medically Attended Adverse Events (MAAEs)
Time Frame
From first vaccine to 12 months after last vaccine on study.
Other Pre-specified Outcome Measures:
Title
Hepatitis B surface antigen-specific antibodies
Description
Change in hepatitis B surface antigen-specific antibody (anti-HBsAg)-producing B-cells
Time Frame
baseline to day 56
Title
Anti-HBsAg Seroconversion
Description
Number of patients with anti-HBsAg seroconversion
Time Frame
Day 0 through 12 months post vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
In order to participate in this study, an individual must meet all the following criteria:
>18 years old
Diagnosed with CHB infection, without HIV, hepatitis C nor hepatitis D co-infections
Currently receiving OAV with HBV VL <100 IU/ml for ≥ 12 months
Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, and other study procedures.
Determined by medical history, targeted physical examination, and clinical judgement of the investigator to be in good health.
CHB infection is defined as any individual with documentation of the following in the past:
• Positive HBsAg and/or detectable HBV DNA test
Exclusion Criteria:
A participant will be ineligible to participate on this study if any of the following criteria are met:
Pregnancy or breast feeding.
Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥ 20 mg/day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to Day 1.
Received or plans to receive live virus vaccines within 4 weeks, and inactivated vaccine within 2 weeks prior to randomization; or plans to receive a non-study vaccine within 28 days after any dose of study vaccine (with exception for seasonal influenza vaccine within 14 days of study vaccine).
Administration of any blood products within 3 months prior to randomization.
Participation in a study with an investigational study product or device within 30 days of randomization.
Has allergies to any hepatitis B and/or yeast-based vaccines.
Subjects meeting any of the following laboratory parameters at screening:
ALT greater than 3 times the upper limit of normal
Elevated total bilirubin WITH direct bilirubin greater than 2 times upper limit of normal
Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as ≥ 38.0°C/100.4°F). Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
Have any chronic or acute or unstable conditions that the investigator considers a contraindication to study participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lydia Tang, MBChB
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Human Virology, University of Maryland School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Dr Sang V Tran Internal Medicine Practice
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22044
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
TLR-9 Adjuvanted Vaccination for Chronic Hepatitis B
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