A Study to Characterise Immune Responses Following Immunisations With "Fendrix" or "Engerix B" Hepatitis B Vaccines

NCT ID: NCT02032160

Last Updated: 2016-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-02-29

Brief Summary

The purpose of this study is to generate an exploratory training set of data and to identify predictive biomarkers (a measurable biological response that predicts something) of innate and adaptive responses to immunisation of two vaccines utilizing different adjuvant technology given according to approved schedules to healthy adult volunteers. The vaccines are model agents selected as they match antigens but have discordant adjuvants, have a known immunogenicity profile, assays are freely available to measure responses, and they are safe to administer to healthy adults at the doses and schedules proposed. This study will strive to correlate biomarker activity with observed immunological responses to vaccination and if successful, these biomarkers could be used in early stage clinical trials to optimize selection of vaccine candidates with a profile that will be most likely to be effective once they are in generalized use.

Detailed Description

The purpose of this study is to generate an exploratory training set of data and to identify predictive biomarkers (a measurable biological response that predicts something) of innate and adaptive responses to immunisation of two vaccines utilizing different adjuvant technology given according to approved schedules to healthy adult volunteers. The vaccines are model agents selected as they match antigens but have discordant adjuvants, have a known immunogenicity profile, assays are freely available to measure responses, and they are safe to administer to healthy adults at the doses and schedules proposed. This study will strive to correlate biomarker activity with observed immunological responses to vaccination and if successful, these biomarkers could be used in early stage clinical trials to optimize selection of vaccine candidates with a profile that will be most likely to be effective once they are in generalized use.

In this study, 15 subjects per vaccine will be recruited to receive immunization with one of two hepatitis B vaccines, Engerix B or Fendrix, representing exactly matched antigens (hepatitis B surface antigen) but discordant adjuvant technologies. Following a screening visit, subjects will be randomly allocated to receive three doses of a vaccine at 0, 1 and 2 months. Innate immune responses (cytokine levels and whole blood gene expression) after doses #1 and #3 and adaptive immune responses (serum antibody and antigen specific cellular responses) will be measured at various timepoints after immunisation on an outpatient basis.

The study is funded by ADITEC, which is a collaborative research programme that aims to accelerate the development of novel and powerful immunisation technologies for the next generation of human vaccines.

Conditions

Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Engerix B

Engerix B IM injection - 20ug At 0, 1 and 6 months

Group Type: EXPERIMENTAL

Engerix B IM injection - 20ug

Intervention Type: BIOLOGICAL

Engerix B IM injection - 20ug At 0, 1 and 6 months

Fendrix

Fendrix IM injection - 20ug At 0, 1 and 6 months

Group Type: EXPERIMENTAL

Fendrix IM injection - 20ug

Intervention Type: BIOLOGICAL

Fendrix IM injection - 20ug At 0, 1 and 6 months

Interventions

Engerix B IM injection - 20ug

Engerix B IM injection - 20ug At 0, 1 and 6 months

Intervention Type: BIOLOGICAL

Fendrix IM injection - 20ug

Fendrix IM injection - 20ug At 0, 1 and 6 months

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Healthy male subjects aged 18-55 years inclusive

2. The subject is, in the opinion of the investigator, healthy on the basis of a physical examination, medical history, blood results, vital signs, with no active disease process that could interfere with the study endpoints.

3. The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.

4. The subject has signed the ICF.

5. The subject has not previously received a vaccine for Hepatitis B or contracted Hepatitis B infection.

6. The subject is seronegative to Hepatitis B as confirmed at screening by assessments of sAb, sAg, and cAb.

7. Seronegative for HIV 1 & 2 antibodies and hepatitis C antibodies at screening.

8. Available for follow-up for the duration of the study.

9. Agree to abstain from donating blood during and for three months after the end of their participation in the study, or longer if necessary.

10. Visa long enough allowing them to complete the study (if applicable).

11. The subject has venous access sufficient to allow blood sampling as per the protocol.

Exclusion Criteria

1. Known hypersensitivity to any component of the vaccines (excipients: sodium chloride, disodium phosphate dehydrate, sodium dihydrogen phosphate; adjuvants: aluminium phosphate, AS04C, aluminium hydroxide; Hepatitis B antigen produced in yeast cells) or subjects who have exhibited hypersensitivity to any other Hepatitis B vaccine, or a history of any allergy that in the opinion of the investigator would contraindicate subject participation.

2. Presence of primary or acquired immunodeficiency states with a total lymphocyte count less than 1,200 per mm3 or presenting other evidence of lack of cellular immune competence e.g. leukaemias, lymphomas, blood dyscrasias, or patients receiving immunosuppressive therapy (including regular use of oral, inhaled, topical or parenteral corticosteroids).

3. Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1 (screening).

4. Regular use of non-steroidal anti-inflammatory drugs (by any route of administration including topical) within 6 months of Visit 1 (screening) considered by the study physician as likely to interfere with immune responses.

5. Receipt of a vaccine within 30 days of visit 2. Other vaccines (e.g. for travel) may be administered between visit 13 and 14 only.

6. Currently participating in another clinical study with an investigational or non-investigational drug or device, or has participated in a clinical study within the 3 months preceding Visit 1.

7. Any condition that, in the investigator's opinion, compromises the subject's ability to meet protocol requirements or to complete the study.

8. Receipt of blood products or immunoglobin, or blood donation, within 3 months of screening.

9. Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Surrey

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David JM Lewis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Surrey

Locations

Surrey Clinical Research Centre

Guildford, Surrey, United Kingdom

Countries

United Kingdom

Other Identifiers

CRC306B

Identifier Type: -

Identifier Source: org_study_id