Evaluation of Non-typable Haemophilus Influenzae and Pneumococcal Protein Vaccine Formulations in Young Adults

Study Overview
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Brief Summary
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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
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This Protocol Posting has been updated following amendment of the Protocol, January 2010. The sections impacted are: study design and study endpoints.

Official Title
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A Study to Evaluate GlaxoSmithKline (GSK) Biologicals' Investigational Vaccination Regimen in Healthy Young Adults

Conditions
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Streptococcus Pneumoniae, Haemophilus Influenzae

Intervention / Treatment
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* Biological: GSK2231395A
* Biological: Engerix-B


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2254233A Group<br>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. | Biological: GSK2231395A<br>* 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.<br>|
| Experimental: GSK2254232A Group<br>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. | Biological: GSK2231395A<br>* 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.<br>|
| Active Comparator: Engerix Group<br>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. | Biological: Engerix-B<br>* Two doses will be administered intramuscularly; one dose at Month 0 and the second dose a Month 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | During a 7-day follow up period after any 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. | During a 30-day (Days 0-29) follow up period after any vaccination | 
| 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. | From Day 0 to Day 420 | 
| 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. | During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420 | 
| 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. | During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420. | 
| 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. | During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 0, 30, 60, 90, 180 and 420. | 
| 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. | Prior to first vaccination (Day 0), at 14 days post vaccination 1 (Day 14) and 2 (Day 74) and at Day 480. | 
| 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). | Prior to first vaccination (Day 0), at 14 days post vaccination 1 (Day 14) and 2 (Day 74) and at Day 480. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-typable Haemophilus influenzae, protein vaccine, Streptococcus pneumoniae, young adults