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

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

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

Interventional

Enrollment (Actual)

13

Phase

  • 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

    • 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

Ages Eligible for Study

16 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
Intervention / Treatment
Active Comparator: Engerix B
15 subjects per group (n = 30 in total)

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)

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

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

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.

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)

July 23, 2015

Primary Completion (Actual)

June 10, 2022

Study Completion (Actual)

June 10, 2022

Study Registration Dates

First Submitted

April 30, 2015

First Submitted That Met QC Criteria

May 4, 2015

First Posted (Estimate)

May 5, 2015

Study Record Updates

Last Update Posted (Actual)

September 29, 2022

Last Update Submitted That Met QC Criteria

September 28, 2022

Last Verified

September 1, 2022

More Information

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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