Evaluation of a Booster Dose of Pneumococcal Vaccine Formulations in Young Adults

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of a booster dose of pneumococcal vaccines (GSK 2189242A) in young adults. This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT 00707798)

Official Title
-----------------
A Study to Evaluate Safety and Immunogenicity of a Booster Dose of Two Formulations of GSK Biologicals' Pneumococcal Candidate Vaccine in Healthy Young Adults

Conditions
-----------------
Infections, Streptococcal

Intervention / Treatment
-----------------
* Biological: Pneumococcal vaccine GSK2189242A (formulation 1)
* Biological: Pneumococcal vaccine GSK2189242A (formulation 2)


Participation Criteria
=================
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 41 years old at the time of vaccination. Subjects who previously participated in the study NCT00707798 and received one of the two investigational GSK2189242A vaccine formulations during the primary study. Written informed consent obtained from the subject. Free of obvious health problems as established by medical history, clinical examination and clinical laboratory assessment before entering into the study. Female subjects of non-childbearing potential (defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause) may be enrolled in the study. 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 vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after vaccination. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the vaccination, or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to the vaccination and ending one month (minimum 30 days) after vaccination. Administration of any pneumococcal vaccine other than the study vaccine during the period between end of study NCT00707798 and study vaccination. Bacterial pneumonia within the period between end of study NCT00707798 and study vaccination. Invasive pneumococcal disease (IPD) within the period between end of study NCT00707798 and study vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection (no laboratory testing required). History of thrombocytopenia or bleeding disorder. Anaphylactic reaction following the previous administration of the vaccine or history of reactions or allergic disease likely to be exacerbated by any component of the vaccine. Current serious neurologic or mental disorders. Inflammatory processes such as known chronic active infections (e.g. Hepatitis B, C). All past or current malignancies (excluding non-melanic skin cancer) and lymphoproliferative disorders. Acute disease at the time of enrolment/vaccination. Fever at the time of vaccination. Fever is defined as temperature >= 37.5°C on oral setting. Physical examination positive for acrocyanosis, jaundice, splenomegaly. Acute or chronic, clinically significant anaemia, pulmonary, cardiovascular, hematologic, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, at the discretion of the investigator Administration of immunoglobulins and/or any blood products within the three months preceding vaccination or planned administration during the study period. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Formulation 1<br> | Biological: Pneumococcal vaccine GSK2189242A (formulation 1)<br>* One dose will be administered intramuscularly at Study Day 0.<br>|
| Experimental: Formulation 2<br> | Biological: Pneumococcal vaccine GSK2189242A (formulation 2)<br>* One dose will be administered intramuscularly at Study Day 0.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 7-day (Days 0-6) post-booster vaccination period | 
| Number of Subjects With Grade 3 and Vaccine-related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, malaise, myalgia and fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = general symptom assessed by the investigator to be casually related to the study vaccination. | During the 7-day (Days 0-6) post-booster vaccination period | 
| Number of Subjects With Grade 3 and Vaccine-related Unsolicited Adverse Events (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During the 31-day (Days 0-30) post-booster vaccination period | 
| Number of Subjects With Any Vaccine-related Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (from Day 0 to Day 30) | 
| Number of Subjects With Grade 3 Haematological or Biochemical Abnormalities | Among haematological or biochemical abnormalities assessed were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Cholesterol, Creatine Phosphokinase (CRP), Hemoglobin decrease, Haemoglobin, Lactate dehydrogenase (LDH), Neutrophils, Red blood cells (RBC), Reticulocytes, White blood cells (WBC) and Overall parameters. Assessment of intensity: Grading of the haematological and biochemical parameters was performed using the standard Food and Drug Administration (FDA) Toxicity Grading Scale. Changes compared to normal reference ranges were graded: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening | At Days 1 and 6 post-booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Histidine Triad Protein D (PhtD) Proteins | Anti-dPly and anti-PhtD antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in LU/mL. The reference seropositivity cut-off values were equal to or above (≥) 599 LU/mL for anti-dPly and ≥ 391 LU/mL for anti-PhtD. | Prior to the booster vaccination (Day 0) and one month post-booster vaccination (Day 30) | 
| Titers for Antibodies Against Pneumolysin Haemolysis (Hem-dPly) Protein | Antibody titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 6. | Prior to the booster vaccination (Day 0) and one month post-booster vaccination (Day 30) | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During the 7-day (Days 0-6) post-booster vaccination period | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, malaise, myalgia and fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. | During the 7-day (Days 0-6) post-booster vaccination period | 
| Number of Subjects With Any Unsolicited AEs | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-day (Days 0-30) post-booster vaccination period | 
| Number of Subjects With Any SAEs | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (from Day 0 to Day 30) | 
| Number of Subjects With Grade 1, Grade 2 and Grade 4 Haematological or Biochemical Abnormalities | Among haematological or biochemical abnormalities assessed were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Cholesterol, Creatine Phosphokinase (CRP), Hemoglobin decrease, Haemoglobin, Lactate dehydrogenase (LDH), Neutrophils, Red blood cells (RBC), Reticulocytes, White blood cells (WBC) and Overall parameters. Assessment of intensity: Grading of the haematological and biochemical parameters was performed using the standard Food and Drug Administration (FDA) Toxicity Grading Scale. Changes compared to normal reference ranges were graded: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening | At 1 and 6 days post-booster vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pneumococcal vaccine, Streptococcus pneumoniae, Young adults