A Pilot Study Comparing the Immunogenicity of Fendrix vs. Double-dose Engerix B in HIV-infected Non-responders to Standard Hepatitis B Vaccination Courses

September 28, 2022 updated by: Sheffield Teaching Hospitals NHS Foundation Trust

Hepatitis B virus (HBV) infection can result in a greater risk of adverse outcomes in HIV-infected individuals, including more rapid progression to cirrhosis and associated complications such as hepatocellular carcinoma. For this reason, as well as the shared routes of transmission between the two viruses, UK and International guidance recommends that all HBV-negative HIV-infected individuals be offered vaccination against HBV. Unfortunately, response rates in this population can be as low as 17.5 - 40% to standard vaccination courses. To improve this response, strategies such as the use of double dose of standard vaccines (e.g. Engerix B) is recommended in several guidelines for previous non-responders, although there is currently limited evidence for this approach. An alternative strategy is to use vaccines with novel adjuvants such as Fendrix and observational clinical data in the Investigators HIV cohort suggests that response rates can be as high as 81% of individuals achieving HBV surface antibody (HBsAb) levels >100 in a group that did not respond to previous standard HBV vaccine courses. However, the cost of Fendrix is considerably higher than Engerix B and controlled trials are required to confirm whether this approach is warranted. Furthermore, insights into the potential mechanisms by which Fendrix may elicit better responses would be valuable in optimising future vaccine strategies in this population.

The Investigators propose to conduct a randomised, open label, active-controlled pilot study comparing double dose Engerix B and Fendrix in HIV-infected non-responders to standard HBV vaccine courses, which will provide the necessary data to design and power a larger multicentre randomised controlled trial. Outcome measures will include the proportion of individuals seroconverting with HBsAb levels >100 following each vaccination course, the magnitude and quality of the HBV-specific CD4+ T-cell responses elicited by each vaccine and the durability of the HBsAb response at 1 year following the end of vaccination.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To compare the immunological responses in HIV-infected non-responders to standard hepatitis B vaccination courses to immunization with either double-dose Engerix B or Fendrix:

  1. Investigators will measure the proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml at 8 weeks after the immunisation course, as well as the durability of this response at 1 year following the completion of the course. The primary aim will be to provide some preliminary data from a head to head study of these two approaches with which to power a larger multi-centre randomized controlled trial.
  2. Investigators will define the magnitude and quality of the Hepatitis B-specific CD4+ T-cell response following vaccination, thus obtaining key immunological data to fill the knowledge gap in T-cell responses to Hepatitis B vaccination, required to support the rationale design of future multi-centre, randomized study comparing vaccination strategies in HIV-infected non-responders to standard Hepatitis B vaccine courses.

The research is original. There is only one published study to date looking at the efficacy of double-dose Engerix B in HIV-infected non-responders to standard courses1. There is currently anecdotal experience of the use of Fendrix in this group from the Investigators cohort and others. There are no head-to-head comparisons of these two strategies.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18
  • HIV-1 infected
  • On antiretroviral therapy
  • Viral load undetectable (for at least 6 months, last available measurement within 3 months)
  • History of having received at least one complete course of non-Fendrix-based hepatitis B vaccination in the past. Patients who have already received a double-dose Engerix B course in the past will still be eligible.
  • HBsAb levels persistently <10IU/L despite vaccination

Exclusion Criteria:

  • A history of hypersensitivity to any previous hepatitis B vaccination
  • A history of hypersensitivity to any components of either Engerix B or Fendrix (see Summary of Product Characteristics).
  • Currently undergoing an incomplete course of any hepatitis B vaccination
  • Having received at least one vaccination with Fendrix in the past
  • Recipient of any other vaccination within the last 2 weeks
  • Any previously detectable HBsAb level (≥10)
  • Pregnant or breastfeeding
  • Individuals who have a current severe febrile illness
  • Individuals with a known and current history of anaemia or any symptoms (shortness of breath, chronic fatigue, chest pain or pallor) suggestive of possible anaemia or haemoglobin below the lower limit of sex adjusted normal range on a full blood count taken within the last 3 months.
  • Current (active) participation in any clinical trial
  • Inability to communicate in English or convey willingness to participate
  • End Stage Renal Disease undergoing renal replacement therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Engerix B
15 subjects per group (n = 30 in total)
Drug: Engerix B

Engerix B 20 micrograms/1ml Licensee: GlaxoSmithKline UK Intra-muscular

Prescription and administration:

The vaccine will be stored in the Investigators pharmacy as clinical trial stock and dispensed on a subject by subject basis.

Shelf life and storage The product must be kept refrigerated (2°C - 8°C). Prescriptions will be written and dispensed from pharmacy on the day of consent, screening and vaccination. The shelf life is 3 years.
Active Comparator: Fendrix
15 subjects per group (n = 30 in total)
Drug: Fendrix

Fendrix suspension for injection GlaxoSmithKline UK

Route of Administration, dose regimen:

Intra-muscular Dose: 0.5ml (20mcg of Hepatitis B Surface Antigen) per vaccination at baseline and weeks 4, 8 and 24.

Prescription and administration:

The vaccine will be stored in the Investigators pharmacy as clinical trial stock and dispensed on a subject by subject basis.

Packaging and labeling The vaccine will have clinical trial labeling. Shelf-life and storage The product must be kept refrigerated (2°C - 8°C).

The shelf life is 3 years.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Hepatitis B-specific CD4+ T-cell response at 2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
Time Frame: 2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sheffield Teaching Hospitals NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 23, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 10, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 10, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 30, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 5, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STH17302

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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