Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Engerix™-B in Adults With or Without Type 2 Diabetes Mellitus

An Open-label Study to Assess the Immunogenicity and Safety of GSK Biologicals' Hepatitis B Vaccine, Engerix™-B in Adults With or Without Type 2 Diabetes Mellitus

This study will evaluate the immunogenicity and safety of Engerix™-B (hepatitis B vaccine) when administered as a primary vaccination course at 0, 1 and 6 months in adults with or without type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: Engerix™-B vaccine

• Study Type: Interventional
• Enrollment (Actual): 667
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • GSK Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • GSK Investigational Site
    • St Albans, Victoria, Australia, 3021
      • GSK Investigational Site
• Canada
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • GSK Investigational Site
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1E8
      • GSK Investigational Site
    • Sudbury, Ontario, Canada, P3E 1H5
      • GSK Investigational Site
  • Quebec
    • Quebec City, Quebec, Canada, G1E 7G9
      • GSK Investigational Site
    • Ste-Foy, Quebec, Canada, G1W 4R4
      • GSK Investigational Site
• New Zealand
  • Hamilton, New Zealand, 3240
    • GSK Investigational Site
  • Rotorua, New Zealand, 3010
    • GSK Investigational Site
  • Takapuna Auckland, New Zealand
    • GSK Investigational Site
  • Wellington, New Zealand, 6021
    • GSK Investigational Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • GSK Investigational Site
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • GSK Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83642
      • GSK Investigational Site
  • Indiana
    • Mishawaka, Indiana, United States, 46545
      • GSK Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67207
      • GSK Investigational Site
  • New York
    • Endwell, New York, United States, 13760
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • GSK Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • GSK Investigational Site
  • Washington
    • Wenatchee, Washington, United States, 98801
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• A male or female subject aged 20 years and above at the time of screening.
• Written informed consent obtained from the subject at screening.
• Subjects diagnosed with type 2 diabetes documented within the past five years, according to the criteria specified by the American Diabetes Association or currently taking any form of anti-diabetic intervention documented by the investigator; or control subjects with no diagnosis or documented history of diabetes, and HbA1c less than 6.5%, as determined by laboratory screening tests.
• Normal renal function defined as estimated glomerular filtration rate (GFR) ≥ 50 mL/min, estimated through the Modification of Diet in Renal Disease (MDRD) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, as determined by laboratory screening tests.
• Seronegative for hepatitis B surface antigen (HBsAg), anti-HBs antibodies and antibodies to hepatitis B core antigen (anti HBc), as determined by laboratory screening tests.

• Female subjects of non-childbearing potential may be enrolled in the study.

  • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

  • has practiced adequate contraception for 30 days prior to vaccination, and
  • has a negative pregnancy test on the day of screening and at Visit 1, and
  • has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Administration of long-acting immune-modifying drugs within 6 months of the study entry or planned administration at any time during the study period.
• Administration of a vaccine not foreseen by the study protocol starting from 30 days before each dose of vaccine and ending 30 days after each dose, with the exception of the inactivated influenza vaccine which is allowed at any time during the study if administered at a separate site.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a protocol-specified non-investigational product.
• Any previous complete or incomplete vaccination against hepatitis B since birth.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection, based on medical history and physical examination.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine, including latex.
• Advanced heart failure or any other severe clinical condition that significantly reduces the subject's life expectancy.
• Acute disease and/or fever at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
• Any history of alcohol or drug abuse in the past 5 years.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diabetes Group; Subjects diagnosed with type 2 diabetes within the five year period before study start who received 3 doses of Engerix™-B vaccine (HBV) at 0, 1 and 6 months. The vaccine was administered intramuscularly (IM) into the deltoid region of the non-dominant arm.	Biological: Engerix™-B vaccine; 3 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.; Other Names: HBV
Active Comparator: Control Group; Subjects with no diagnosis or documented history of diabetes who received 3 doses of Engerix™-B (HBV) vaccine at 0, 1 and 6 months. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: Engerix™-B vaccine; 3 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.; Other Names: HBV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroprotected for Anti- Hepatitis B Surface Antigen (Anti-HBs) Antibodies	A seroprotected subject was defined as a vaccinated subject with an anti-HBs antibody concentration greater than or equal to (≥) 10 milli-international units per milliliter (mIU/mL).	At one month after the third dose of primary vaccination (Month 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-HBs Antibody Concentration	Concentrations were given as geometric mean concentration (GMC) and expressed as mIU/mL	At one month after the third dose of primary vaccination (Month 7)
Number of Subjects Reporting Any Solicited Local Symptoms	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity grade.	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects Reporting Any Solicited General Symptoms	Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Any fever = oral temperature greater than or equal to (≥) 37.5 degrees Celsius (°C)	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs)	An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.	During the 31-day (Days 0-30) post-vaccination period
Number of Subjects Reporting Any Serious Adverse Events (SAEs)	A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination.	During the entire study period (Month 0 - Month 7)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Van Der Meeren O, Peterson JT, Dionne M, Beasley R, Ebeling PR, Ferguson M, Nissen MD, Rheault P, Simpson RW, De Ridder M, Crasta PD, Miller JM, Trofa AF. Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus. Hum Vaccin Immunother. 2016 Aug 2;12(8):2197-2203. doi: 10.1080/21645515.2016.1164362. Epub 2016 Apr 28.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: July 24, 2012
• Primary Completion (Actual): December 18, 2013
• Study Completion (Actual): December 18, 2013

Study Registration Dates

• First Submitted: June 21, 2012
• First Submitted That Met QC Criteria: June 21, 2012
• First Posted (Estimate): June 25, 2012

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; hepatitis B; adults; Engerix™-B
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Endocrine System Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: 115918

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 115918
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 115918
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 115918
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 115918
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 115918
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 115918
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register