Back to resultsEvaluation of Non-typable Haemophilus Influenzae and Pneumococcal Protein Vaccine Formulations in Young Adults
Primary Purpose
Streptococcus Pneumoniae, Haemophilus Influenzae
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
GSK2231395A
Engerix-B
Sponsored by
About this trial
This is an interventional prevention trial for Streptococcus Pneumoniae focused on measuring Non-typable Haemophilus influenzae, protein vaccine, Streptococcus pneumoniae, young adults
Eligibility Criteria
Inclusion Criteria:
- Subjects who the investigator believes will comply with the requirements of the protocol should be enrolled in the study.
- A male or female between, and including, 18 and 40 years of age at the time of the first vaccination.
- Written informed consent obtained from the subject.
- Subject without medical history, clinical finding or laboratory finding, which, in the opinion of the investigator, could pose a safety concern or interfere with the protocol.
- If the subject is female, and of childbearing potential, she agrees to use adequate contraception and not become pregnant for the duration of the study.
Exclusion Criteria:
- Pneumonia within 3 years prior to 1st vaccination.
- Invasive Pneumococcal Disease within 3 years prior to 1st vaccination.
- Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
- Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccines, with the exception of the influenza vaccine which can be administered >14 days prior to or >14 days following vaccine doses 1 and 2.
- Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
- History of reaction or hypersensitivity to any component of the vaccine.
- Any serious, uncontrolled disease likely to interfere with the study as determined by history, physical examination or laboratory screening, as per the judgment of the Investigator.
- Inflammatory processes such as known chronic infections.
- All past or current malignancies and lymphoproliferative disorders.
- Laboratory evidence of haematological and biochemical abnormalities.
- Acute disease at the time of enrolment/vaccination.
- Pregnant or lactating female.
- Female planning to become pregnant or planning to discontinue contraceptive precautions.
- History of chronic alcohol consumption and/or drug abuse.
- Other conditions that the principal investigator judges may interfere with study findings.
- Previous vaccination for hepatitis B. As a portion of the subjects will be randomized to receive Engerix-B comparator, it is important that all subjects meet Engerix-B eligibility criteria.
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
GSK2254233A Group
GSK2254232A Group
Engerix Group
Arm Description
Subjects received 2 doses of adjuvanted Non-Typable Haemophilus influenza and pneumococcal vaccine GSK2254233A at Months 0 and 2. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.
Subjects received 2 doses of non-adjuvanted Non-Typable Haemophilus influenza and pneumococcal vaccine GSK2254232A at Months 0 and 2. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.
Subjects received 3 doses of Engerix vaccine at Months 0, 2 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.
Outcomes
Primary Outcome Measures
Number of Subjects With Any Solicited Local and General Symptoms
Solicited local symptoms assessed were pain, redness and swelling. Any solicited local symptom was defined as occurrence of any solicited local symptom regardless of intensity grade.
Solicited general symptoms assessed were fatigue, gastrointestinal, headache, malaise, myalgia and temperature Any temperature was defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C). For other symptoms: Any = any general symptom reported irrespective of intensity grade and relationship to vaccination.
Number of Subjects With Any Unsolicited Adverse Events (AE)
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
Number of Subjects With Any Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are 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.
Number of Subjects With Any Biochemical Laboratory Abnormalities
Biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) and urea (URE).
Abnormalities reported include values outside the normal ranges. Time points were presented as before (Pre) or after (Post) Dose 1, 2 or 3.
Number of Subjects With Any Hematological Laboratory Abnormalities
Hematological parameters assessed in blood samples include red blood cells (RBC), white blood cells (WBC - including Basophils (BAS), neutrophils (NEU), lymphocytes (LYM), eosinophils (EOS) and monocytes (MON), blood platelets (PLA) and Hemoglobin (HEM). Abnormalities reported include values outside the normal ranges.
This outcome presents results for RBC, WBC High and Low, PLA and HEM. Time points were presented as before (pre) or after (post) doses 1, 2 or 3.
Number of Subjects With Any Hematological Laboratory Abnormalities
Hematological parameters assessed in blood samples include red blood cells (RBC), white blood cells (WBC - including Basophils (BAS), neutrophils (NEU), lymphocytes (LYM), eosinophils (EOS) and monocytes (MON)), blood platelets (PLA) and Hemoglobin (HEM). Abnormalities reported include values outside the normal ranges.
This outcome presents results for BAS, NEU, LYM, EOS and MON. Time points were presented as before (Pre) or after (Post) Dose 1, 2 or 3.
Secondary Outcome Measures
Concentrations of Antibodies Against Protein D (Anti-PD), Pneumolysin (Anti-Ply) and Pneumococcal Histidine Triad D (Anti-PhtD)
Concentrations were given as Geometric Mean Concentrations (GMCs). The cut-off values were 112 Luminex Units per milliliter (LU/mL) for Anti-PD, 391 LU/mL for Anti-PhtD and 591 LU/mL for Anti-Ply.
Mean Number of Influenza-specific Cluster of Differentiation (CD) 4 T-cells.
The mean number was calculated for CD4+ cells stimulated by protein D (PD), pneumococcal histidine triad D (PhtD) or pneumolysin toxoid (dPly), identified as producing T-lymphocyte Helper 1 cells (Th1) versus Th2 cytokines (interferon-gamma (IFN-g) and interleukin-13 (IL-13) respectively, as measured by intracellular staining (ICS) on Peripheral Blood Mononuclear Cells (PBMCs). The outcome presents results for cells producing the following combinations:
Th1=IFN-g, Th 2=IL13 and/or IL5 and Th17=IL17.
Mean Number of Influenza-specific Cluster of Differentiation (CD) 8 T-cells.
The mean number was calculated for CD8+ cells stimulated by protein D (PD), pneumococcal histidine triad D (PhtD) and pneumolysin toxoid (dPly) and expressing the following citokine combinations:
C1= at least interleukin 2 (IL2), tumor necrosis factor alpha (TNFa) and/or interferon-gamma (IFNg) and C2= at least interleukin 17 (IL17).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00814489
Brief Title
Evaluation of Non-typable Haemophilus Influenzae and Pneumococcal Protein Vaccine Formulations in Young Adults
Official Title
A Study to Evaluate GlaxoSmithKline (GSK) Biologicals' Investigational Vaccination Regimen in Healthy Young Adults
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
January 8, 2009 (undefined)
Primary Completion Date
May 4, 2009 (Actual)
Study Completion Date
June 10, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of 2 formulations of a non-typable Haemophilus influenzae and pneumococcal candidate vaccine in young adults. Subjects will be vaccinated 2 times in an observer-blind manner with an interval of 2 months. The subjects receiving Engerix-B will receive in an open-manner a third dose of the vaccine at Month 6. The protocol posting has been updated following a protocol amendment.
Detailed Description
This Protocol Posting has been updated following amendment of the Protocol, January 2010. The sections impacted are: study design and study endpoints.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Streptococcus Pneumoniae, Haemophilus Influenzae
Keywords
Non-typable Haemophilus influenzae, protein vaccine, Streptococcus pneumoniae, young adults
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK2254233A Group
Arm Type
Experimental
Arm Description
Subjects received 2 doses of adjuvanted Non-Typable Haemophilus influenza and pneumococcal vaccine GSK2254233A at Months 0 and 2. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.
Arm Title
GSK2254232A Group
Arm Type
Experimental
Arm Description
Subjects received 2 doses of non-adjuvanted Non-Typable Haemophilus influenza and pneumococcal vaccine GSK2254232A at Months 0 and 2. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.
Arm Title
Engerix Group
Arm Type
Active Comparator
Arm Description
Subjects received 3 doses of Engerix vaccine at Months 0, 2 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.
Intervention Type
Biological
Intervention Name(s)
GSK2231395A
Intervention Description
Two doses will be administered intramuscularly; one dose at Month 0 and the second dose a Month 2. Two different formulations of this vaccine will be tested.
Intervention Type
Biological
Intervention Name(s)
Engerix-B
Intervention Description
Two doses will be administered intramuscularly; one dose at Month 0 and the second dose a Month 2.
Primary Outcome Measure Information:
Title
Number of Subjects With Any Solicited Local and General Symptoms
Description
Solicited local symptoms assessed were pain, redness and swelling. Any solicited local symptom was defined as occurrence of any solicited local symptom regardless of intensity grade.
Solicited general symptoms assessed were fatigue, gastrointestinal, headache, malaise, myalgia and temperature Any temperature was defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C). For other symptoms: Any = any general symptom reported irrespective of intensity grade and relationship to vaccination.
Time Frame
During a 7-day follow up period after any vaccination
Title
Number of Subjects With Any Unsolicited Adverse Events (AE)
Description
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
Time Frame
During a 30-day (Days 0-29) follow up period after any vaccination
Title
Number of Subjects With Any Serious Adverse Events (SAEs)
Description
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are 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
From Day 0 to Day 420
Title
Number of Subjects With Any Biochemical Laboratory Abnormalities
Description
Biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) and urea (URE).
Abnormalities reported include values outside the normal ranges. Time points were presented as before (Pre) or after (Post) Dose 1, 2 or 3.
Time Frame
During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420
Title
Number of Subjects With Any Hematological Laboratory Abnormalities
Description
Hematological parameters assessed in blood samples include red blood cells (RBC), white blood cells (WBC - including Basophils (BAS), neutrophils (NEU), lymphocytes (LYM), eosinophils (EOS) and monocytes (MON), blood platelets (PLA) and Hemoglobin (HEM). Abnormalities reported include values outside the normal ranges.
This outcome presents results for RBC, WBC High and Low, PLA and HEM. Time points were presented as before (pre) or after (post) doses 1, 2 or 3.
Time Frame
During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420.
Title
Number of Subjects With Any Hematological Laboratory Abnormalities
Description
Hematological parameters assessed in blood samples include red blood cells (RBC), white blood cells (WBC - including Basophils (BAS), neutrophils (NEU), lymphocytes (LYM), eosinophils (EOS) and monocytes (MON)), blood platelets (PLA) and Hemoglobin (HEM). Abnormalities reported include values outside the normal ranges.
This outcome presents results for BAS, NEU, LYM, EOS and MON. Time points were presented as before (Pre) or after (Post) Dose 1, 2 or 3.
Time Frame
During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420.
Secondary Outcome Measure Information:
Title
Concentrations of Antibodies Against Protein D (Anti-PD), Pneumolysin (Anti-Ply) and Pneumococcal Histidine Triad D (Anti-PhtD)
Description
Concentrations were given as Geometric Mean Concentrations (GMCs). The cut-off values were 112 Luminex Units per milliliter (LU/mL) for Anti-PD, 391 LU/mL for Anti-PhtD and 591 LU/mL for Anti-Ply.
Time Frame
Days 0, 30, 60, 90, 180 and 420.
Title
Mean Number of Influenza-specific Cluster of Differentiation (CD) 4 T-cells.
Description
The mean number was calculated for CD4+ cells stimulated by protein D (PD), pneumococcal histidine triad D (PhtD) or pneumolysin toxoid (dPly), identified as producing T-lymphocyte Helper 1 cells (Th1) versus Th2 cytokines (interferon-gamma (IFN-g) and interleukin-13 (IL-13) respectively, as measured by intracellular staining (ICS) on Peripheral Blood Mononuclear Cells (PBMCs). The outcome presents results for cells producing the following combinations:
Th1=IFN-g, Th 2=IL13 and/or IL5 and Th17=IL17.
Time Frame
Prior to first vaccination (Day 0), at 14 days post vaccination 1 (Day 14) and 2 (Day 74) and at Day 480.
Title
Mean Number of Influenza-specific Cluster of Differentiation (CD) 8 T-cells.
Description
The mean number was calculated for CD8+ cells stimulated by protein D (PD), pneumococcal histidine triad D (PhtD) and pneumolysin toxoid (dPly) and expressing the following citokine combinations:
C1= at least interleukin 2 (IL2), tumor necrosis factor alpha (TNFa) and/or interferon-gamma (IFNg) and C2= at least interleukin 17 (IL17).
Time Frame
Prior to first vaccination (Day 0), at 14 days post vaccination 1 (Day 14) and 2 (Day 74) and at Day 480.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects who the investigator believes will comply with the requirements of the protocol should be enrolled in the study.
A male or female between, and including, 18 and 40 years of age at the time of the first vaccination.
Written informed consent obtained from the subject.
Subject without medical history, clinical finding or laboratory finding, which, in the opinion of the investigator, could pose a safety concern or interfere with the protocol.
If the subject is female, and of childbearing potential, she agrees to use adequate contraception and not become pregnant for the duration of the study.
Exclusion Criteria:
Pneumonia within 3 years prior to 1st vaccination.
Invasive Pneumococcal Disease within 3 years prior to 1st vaccination.
Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccines, with the exception of the influenza vaccine which can be administered >14 days prior to or >14 days following vaccine doses 1 and 2.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
History of reaction or hypersensitivity to any component of the vaccine.
Any serious, uncontrolled disease likely to interfere with the study as determined by history, physical examination or laboratory screening, as per the judgment of the Investigator.
Inflammatory processes such as known chronic infections.
All past or current malignancies and lymphoproliferative disorders.
Laboratory evidence of haematological and biochemical abnormalities.
Acute disease at the time of enrolment/vaccination.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.
History of chronic alcohol consumption and/or drug abuse.
Other conditions that the principal investigator judges may interfere with study findings.
Previous vaccination for hepatitis B. As a portion of the subjects will be randomized to receive Engerix-B comparator, it is important that all subjects meet Engerix-B eligibility criteria.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Karlskrona
ZIP/Postal Code
SE-371 41
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
24173029
Citation
Berglund J, Vink P, Tavares Da Silva F, Lestrate P, Boutriau D. Safety, immunogenicity, and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae triple-protein vaccine in a phase 1 randomized controlled study in healthy adults. Clin Vaccine Immunol. 2014 Jan;21(1):56-65. doi: 10.1128/CVI.00430-13. Epub 2013 Oct 30.
Results Reference
derived
Learn more about this trial
Evaluation of Non-typable Haemophilus Influenzae and Pneumococcal Protein Vaccine Formulations in Young Adults
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