Training Study to Characterise Biomarkers to the Engerix B Vaccine

This study is currently recruiting participants.
Verified September 2013 by University of Surrey
Sponsor:
Collaborators:
Innovative Medicines Initiative.
GlaxoSmithKline
Information provided by (Responsible Party):
University of Surrey
ClinicalTrials.gov Identifier:
NCT01771354
First received: November 15, 2012
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

It is thought that vaccines trigger innate inflammatory responses to induce antigenspecific adaptive immunity (the desired effect), but excessive inflammation may lead to serious inflammatory complications or unwanted side effects. Currently there is a lack of reliable biomarkers (a measurable biological response that predicts something) able to predict severe inflammation and this has resulted in the development of several vaccines being terminated and the withdrawal of some licensed vaccines which were associated with inflammatory complications.

This study is part of the BIOVACSAFE project which is a 5year €30M project funded by the Innovative Medicine Initiative. The project involves a series of clinical studies using licensed vaccines as benchmarks to generate clinical data on inflammation and identify biomarkers that can be used to predict acceptable reactogenicity. The target is to identify biomarkers that can predict the occurrence of beneficial and detrimental effects in response to a vaccine. Such biomarkers could be used in future vaccine development programs to optimize selection of vaccine candidates with a profile that will be unlikely to generate worrisome safety signals once they are in generalized use.

This study is one in a series of "training" studies which will each use different licensed vaccines that are prototypical representatives of a class of vaccine used in a particular target population. Twenty four subjects will be randomised into two groups to receive: A) Engerix B vaccine (n = 20), B) Saline placebo (n = 4). Following a screening visit, participants will undergo two immunisations at month 0 and month 6. Each immunisation will occur during a seven day residential visit which will include immunization and intensive monitoring of physiological (e.g. heart rate, oral temperature, blood pressure) metabolic and immune (innate and adaptive) parameters. Both residential visits will be followed up by four outpatient visits with further monitoring and blood samples.


Condition Intervention Phase
Healthy
Biological: Engerix B Vaccine
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: A Clinical Study to Generate an Exploratory Training Set of Data Characterising Clinical Events, Physiological and Metabolic Responses, and Innate and Adaptive Immune Responses Following the First and Third of Three Intra-muscular Immunisations With "Engerix B" Hepatitis B Vaccine or Saline Placebo in Healthy Adults With no Pre-existing Immunity to Hepatitis B

Resource links provided by NLM:


Further study details as provided by University of Surrey:

Primary Outcome Measures:
  • Change from baseline values of global gene expression in whole blood. [ Time Frame: Visits 1 (Day -28 to -2), 2 (Day -1 to +5) , 3 (Day 7), 4 Day 14), 5 (Day 21), 6 (Day 28), 7 (Day 168 to 173), 8 (Day 175), 9 (Day 182), 10 (day 189), 11 (Day 196). ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Proportion of subjects experiencing vaccine-related clinical events following administration of vaccine. [ Time Frame: Visits 2 (Day -1 to +5) , 3 (Day 7), 4 Day 14), 5 (Day 21), 6 (Day 28), 7 (Day 168 to 173), 8 (Day 175), 9 (Day 182), 10 (day 189), 11 (Day 196). ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: February 2013
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Biological: Placebo
Active Comparator: Vaccine
Engerix B vaccine
Biological: Engerix B Vaccine

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy male or female subjects aged 18-45 years inclusive. Randomisation will ensure equal numbers of men and women.
  2. The subject is, in the opinion of the investigator, healthy on the basis of medical history, vital signs, and the results of routine laboratory tests with no active disease process that could interfere with the study endpoints.
  3. Body Mass Index ≥18.5 and <29.5
  4. The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
  5. The subject has signed the ICF.
  6. The subject has not previously received a vaccine for Hepatitis B or contracted hepatitis B infection.
  7. The subject is seronegative to Hepatitis B as confirmed at screening by assessments of sAb, sAg, and cAb.
  8. Available for followup 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. If heterosexually active female, willing to use an effective method of contraception with partner (any hormonal contraception e.g oral contraceptive pill, progesterone only pill; intrauterine device; injectable or implanted contraceptive; condoms incorporating spermicide if using these; physiological or anatomical sterility) from 30 days prior to, and 3 months after, vaccination. Willing to undergo urine pregnancy tests prior to vaccination and blood pregnancy test at screening and final follow up.
  11. The subject self-reports at screening that for the past month they have had regular sleep pattern with bedtime occurring between 22:00 and 01:00 h.
  12. The subject has venous access sufficient to allow blood sampling as per the protocol.

Exclusion Criteria:

  1. Significant dietary restrictions (e.g. vegan, lactose intolerant, but vegetarian acceptable) or life-threatening food allergies (e.g. anaphylaxis related nut allergies).
  2. Pregnant or lactating at any point during the study from screening to final follow up.
  3. Known hypersensitivity to any component of the vaccine (excipients: sodium chloride, disodium phosphate dehydrate, sodium dihydrogen phosphate; Hepatitis B antigen produced in yeast cells) or subjects who have exhibited hypersensitivity following previous Engerix B administration; or known hypersensitivity to any other hepatitis B vaccine.
  4. 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).
  5. Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1 (screening).
  6. Regular use of nonsteroidal antiinflammatory 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.
  7. Receipt of a vaccine within 30 days of visit 2, or requirement to receive another vaccine within the study period.
  8. Presence of an acute severe febrile illness at time of immunisation.
  9. History of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1.
  10. Currently participating in another clinical trial with an investigational or noninvestigational drug or device, or has participated in a clinical trial within the 3 months preceding Visit 1.
  11. Any condition that, in the investigator's opinion, compromises the subject's ability to meet protocol requirements or to complete the study.
  12. Receipt of blood products or immunoglobin, or blood donation, within 3 months of screening.
  13. Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
  14. An average weekly alcohol intake that exceeds 14 or 21 units per week for females and males, respectively (1 unit = 12 oz or 360ml of beer; 5oz or 150ml of wine; 1.5oz or 45ml of distilled spirits), or unwilling to stop alcohol consumption for each treatment period during the study.
  15. Currently smokes in excess of 5 cigarettes/day or use tobacco or nicotine substitutes (within the last 6 months of screening), or subjects unwilling to refrain from smoking or are unable to abide by Surrey CRC restrictions.
  16. Consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120mg caffeine) of coffee, tea, cola, or other caffeinated beverages/food per day.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01771354

Contacts
Contact: Julia Lawson +44 800 269 847 crc-recruitment@surrey.ac.uk
Contact: Jennifer Stuart +44 800 269 847 crc-recruitment@surrey.ac.uk

Locations
United Kingdom
University of Surrey, Surrey CRC Recruiting
Guildford, Surrey, United Kingdom, GU2 7XP
Principal Investigator: David J Lewis         
Sponsors and Collaborators
University of Surrey
Innovative Medicines Initiative.
GlaxoSmithKline
  More Information

Additional Information:
No publications provided

Responsible Party: University of Surrey
ClinicalTrials.gov Identifier: NCT01771354     History of Changes
Other Study ID Numbers: CRC305B
Study First Received: November 15, 2012
Last Updated: September 17, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Surrey:
Volunteers
Identify
Biomarkers
Vaccine Safety

ClinicalTrials.gov processed this record on April 22, 2014