Hepatitis B
Conditions
Keywords
Engerix™-B, hepatitis B, adults, Type 2 diabetes mellitus
Brief summary
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.
Interventions
BIOLOGICALEngerix™-B vaccine
3 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seroprotected for Anti- Hepatitis B Surface Antigen (Anti-HBs) Antibodies | At one month after the third dose of primary vaccination (Month 7) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HBs Antibody Concentration | At one month after the third dose of primary vaccination (Month 7) | Concentrations were given as geometric mean concentration (GMC) and expressed as mIU/mL |
| Number of Subjects Reporting Any Solicited Local Symptoms | During the 4-day (Days 0-3) post-vaccination period | 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. |
| Number of Subjects Reporting Any Solicited General Symptoms | During the 4-day (Days 0-3) post-vaccination period | 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) |
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) | During the 31-day (Days 0-30) post-vaccination period | 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. |
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | During the entire study period (Month 0 - Month 7) | 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. |
Countries
Australia, Canada, New Zealand, United States
Participant flow
Pre-assignment details
There was re-allocation of 7 subjects conducted due to certain discrepancies between subjects' attributes identified from two different sources and as a result of which, there was an increase in the number of subjects from the 667 subjects targeted initially.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 416 |
| 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. | 258 |
| Total | 674 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 4 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Diabetes Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 53.2 Years STANDARD_DEVIATION 12.32 | 49.6 Years STANDARD_DEVIATION 13.72 | 51.8 Years STANDARD_DEVIATION 12.98 |
| Sex: Female, Male Female | 182 Participants | 152 Participants | 334 Participants |
| Sex: Female, Male Male | 234 Participants | 106 Participants | 340 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 247 / 416 | 168 / 258 |
| serious Total, serious adverse events | 16 / 416 | 4 / 258 |
Outcome results
Primary
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).
Time frame: At one month after the third dose of primary vaccination (Month 7)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects who received all 3 doses of the EngerixTM-B vaccine, for whom post-vaccination immunogenicity results were available and for those in the Control Group, a suitable match was available in the Diabetic Group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diabetes Group | Number of Subjects Seroprotected for Anti- Hepatitis B Surface Antigen (Anti-HBs) Antibodies | 285 Participants |
| Control Group | Number of Subjects Seroprotected for Anti- Hepatitis B Surface Antigen (Anti-HBs) Antibodies | 155 Participants |
Secondary
Anti-HBs Antibody Concentration
Concentrations were given as geometric mean concentration (GMC) and expressed as mIU/mL
Time frame: At one month after the third dose of primary vaccination (Month 7)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects who received all 3 doses of the EngerixTM-B vaccine, for whom post-vaccination immunogenicity results were available and for those in the Control Group, a suitable match was available in the Diabetic Group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Diabetes Group | Anti-HBs Antibody Concentration | 147.6 mIU/mL |
| Control Group | Anti-HBs Antibody Concentration | 384.2 mIU/mL |
Secondary
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.
Time frame: During the entire study period (Month 0 - Month 7)
Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects who received at least one study vaccine administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diabetes Group | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | 16 Participants |
| Control Group | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | 4 Participants |
Secondary
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)
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: The analysis was performed on Total Vaccinated cohort, which included all subjects who received at least one study vaccine administration and had symptom sheet completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diabetes Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Fatigue | 118 Participants |
| Diabetes Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Gastrointestinal symptoms | 83 Participants |
| Diabetes Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Headache | 97 Participants |
| Diabetes Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Fever | 15 Participants |
| Control Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Fever | 8 Participants |
| Control Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Fatigue | 69 Participants |
| Control Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Headache | 71 Participants |
| Control Group | Number of Subjects Reporting Any Solicited General Symptoms | Any Gastrointestinal symptoms | 47 Participants |
Secondary
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.
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: The analysis was performed on Total Vaccinated cohort, which included all subjects who received at least one study vaccine administration and had symptom sheet completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diabetes Group | Number of Subjects Reporting Any Solicited Local Symptoms | Any Pain | 160 Participants |
| Diabetes Group | Number of Subjects Reporting Any Solicited Local Symptoms | Any Redness | 84 Participants |
| Diabetes Group | Number of Subjects Reporting Any Solicited Local Symptoms | Any Swelling | 49 Participants |
| Control Group | Number of Subjects Reporting Any Solicited Local Symptoms | Any Pain | 115 Participants |
| Control Group | Number of Subjects Reporting Any Solicited Local Symptoms | Any Redness | 51 Participants |
| Control Group | Number of Subjects Reporting Any Solicited Local Symptoms | Any Swelling | 19 Participants |
Secondary
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.
Time frame: During the 31-day (Days 0-30) post-vaccination period
Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects who received at least one study vaccine administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diabetes Group | Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) | 150 Participants |
| Control Group | Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) | 96 Participants |