NCT02434848

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

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• HIV
• Communicable Diseases
• Hepatitis B
• HBV
• Infectious Diseases

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2015-07-23
• Primary completion: 2022-06-10
• Completion: 2022-06-10
• First posted: 2015-05-05
• Last updated: 2022-09-29

Locations

1 site across 1 country: United Kingdom