Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age.

Infections, Streptococcal Clinical Trial

Official title:

Primary and Booster Vaccination Course in Human Immunodeficiency Virus (HIV) Infected Infants, HIV Exposed Uninfected Infants and Unexposed Uninfected Infants Receiving the Pneumococcal Vaccine GSK 1024850A.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00829010
• Other study ID #: 111634
• Status: Completed
• Phase: Phase 3
• Start date: February 17, 2009
• Est. completion date: June 27, 2012

Study information

• Verified date: October 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purposes of this study:

• To evaluate the immunogenicity, safety and reactogenicity of pneumococcal vaccine GSK1024850A in HIV infected infants, HIV exposed uninfected infants and HIV unexposed uninfected infants following a 3-dose primary vaccination at 6, 10 and 14 weeks of age and following booster vaccination at 9-10 months of age.

• To evaluate the immunogenicity, safety and reactogenicity of pneumococcal vaccine GSK1024850A in HIV unexposed uninfected infants receiving either a 3-dose primary vaccination according to the EPI vaccination schedule at 6, 10 and 14 weeks of age with or without booster vaccination at 9-10 months of age or a 2-dose primary vaccination at 6 and 14 weeks of age followed by booster vaccination at 9-10 months of age.

• This study also aims to assess the impact of the pneumococcal vaccine GSK1024850A on nasopharyngeal carriage of S. pneumoniae and H. influenzae up to 24 months of age in all study participants.

Description:

This protocol posting has been updated according to Protocol amendment 1, December 08

Recruitment information / eligibility

• Status: Completed
• Enrollment: 489
• Est. completion date: June 27, 2012
• Est. primary completion date: June 13, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 10 Weeks

Eligibility

Inclusion Criteria:

• Male or female subjects between, and including 6-10 weeks of age at the time of the first vaccination.

• Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol.

• Written informed consent obtained from the parent(s)/guardian(s) of the child/ward.

• Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study).

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period.

• A family history of hereditary immunodeficiency other than HIV infection.

• Major congenital defects or serious chronic illness other than HIV infection.

• For HIV infected infants: Moderately and severely symptomatic: stages III and IV according to latest version of WHO classification.

• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

• Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and/or Streptococcus pneumoniae.

• History of, or intercurrent, diphtheria, tetanus, pertussis, and Haemophilus influenzae type b disease.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.

• History of any neurological disorders or seizures.

• Acute disease at the time of enrolment.

• Babies for which weight for age is < 3rd percentile at Visit 1, using standard growth charts, with the exception of HIV infected infants for which the decision of enrolment was left to the investigator's discretion.

• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal (GI) tract, intussusception (IS) or other medical condition determined to be serious by the investigator.

• Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of vaccination).

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• Pneumococcal vaccine GSK1024850A
Intramuscular injection, administered as 3 or 4 doses
• Tritanrix-HepB/Hib
Intramuscular injection, 4 doses
• measles
Intramuscular injection, 2 doses
• Rotarix
Oral, 2 doses
• Local OPV
Oral 4 doses. Given at any time during the study, routinely given concurrently with DTPw-HBV/Hib vaccine

Locations

Country	Name	City	State
South Africa	GSK Investigational Site	Soweto	Gauteng

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL).	Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.	1 month following primary immunization (post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, HIV- (3+0) Group and post-Dose 2 at Month 3 for the HIV- (2+1) Group)
Secondary	Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.	Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups, post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. The cut-off of the assay is 0.05 µg/mL.	At Month 3 and Month 9
Secondary	Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.	Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.	up to study end at Month 23 (24-27 months of age)
Secondary	Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.	Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.	At Month 3 and at Month 9
Secondary	Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.	Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.	up to study end at Month 23 (24-27 months of age)
Secondary	Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.	Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. The cut-off of the assay is 0.05 µg/mL.	At Month 3 and Month 9
Secondary	Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.	Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.	up to study end at Month 23 (24-27 months of age)
Secondary	Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.	Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.	At Month 3 and at Month 9
Secondary	Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.	Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.	up to study end at Month 23 (24-27 months of age)
Secondary	Concentrations of Antibodies Against Protein D (PD) by ELISA	Concentrations of antibodies are presented as GMCs expressed as ELISA units per milliliter (EL.U/mL). The cut-off of the assay was 100 EL.U/mL. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group.	At Month 3 and at Month 9
Secondary	Concentrations of Antibodies Against Protein D (PD) by ELISA.	Concentrations of antibodies are presented as GMCs expressed as ELISA units per milliliter (EL.U/mL). The cut-off of the assay was 100 EL.U/mL. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups.	up to study end at Month 23 (24-27 months of age)
Secondary	Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).	Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL) The cut-off of the assay is 0.1IU/mL.	1 month following primary immunization (at Month 3)
Secondary	Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).	Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL). The cut-off of the assay is 0.1IU/mL.	1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)
Secondary	Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA.	Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.	1 month following primary immunization (at Month 3)
Secondary	Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA .	Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.	1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)
Secondary	Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)	Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.	1 month following primary immunization (at Month 3)
Secondary	Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)	Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.	1 month after the booster vaccination (at Month 15)
Secondary	Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA	Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL). The cut-off of the assay is 10 mIU/mL.; As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table showed results following partial or complete retesting/reanalysis	1 month following primary immunization (at Month 3)
Secondary	Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA.	Concentrations of antibodies were presented as GMCs expressed as milli-International units per milliliter (mIU/mL). The cut-off of the assay was 10 mIU/mL.; As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table showed results following partial or complete retesting/reanalysis	1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)
Secondary	Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.	Concentrations of antibodies are presented as GMCs expressed as units per millilitre (U/mL). The cut-off of the assay is 20 U/mL. Data were collected for subjects who received 1, 2 doses or no Rotarix dose during the study.	1 month after the administration of the second vaccine dose (at Month 3)
Secondary	Concentrations of Antibodies Against Measles	Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL).The cut-off of the assay is 150 mIU/mL.	1 month following administration of the 1st and 2nd vaccine dose (at Months 9 and 15)
Secondary	Anti-LytC IgA and Anti-PhtD IgA Antibodies Concentrations in Salivary Samples	Salivary antibodies against selected common bacterial protein antigens. Salivary samples (1.0 mL) were collected by using an Oracol™ device consisting of a sponge (2 cm3) placed on a stick that was used to brush the teeth and gums to absorb the saliva. Salivary samples were sent to RMPRU (or GSK Biologicals' designated validated laboratory) where the sponge was centrifuged to extract the saliva and that was immediately stored at -70°C. The cut-off of the assay was 2.3 U/mL for anti-LytC IgA and 2.2 U/mL for anti PhtD IgA.	up to study end at Month 23 (24-27 months of age)
Secondary	Number of Swabs With Positive Cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae (Vaccine Serotypes, Cross-reactive or Other Serotypes) and Other Bacterial Pathogens in the Nasopharynx.	Positive cultures of H. influenza* (HI) and S. pneumonia(SP) and other bacterial pathogens such as Moraxella catarrhalis(MC), Group A streptococci and Staphylococcus aureus (SA), identified in the nasopharynx at each swab time point: Month (Mth) 0 (Pre-vaccination time point at 6-12 weeks of age), Mth 3 (18 weeks of age), Mth 8 (9-10 Months of age), Mth 9 (10-11 Months of age), Mth 11 (12-13 Months of age), Mth 14 (15-18 Months of age), Mth 15 (16-19 Months of age) and Mth 23 (24-27 Months of age). *Data presented included only results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay	up to study end at Month 23 (24-27 months of age)
Secondary	Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs	Acquisition of new H. influenza* (HI) and S. pneumonia(SP) strains, identified in the nasopharynx at each swab time point: Month (Mth) 3 (18 weeks of age), Mth 8 (9-10 Months of age), Mth 9 (10-11 Months of age), Mth 11 (12-13 Months of age), Mth 14 (15-18 Months of age), Mth 15 (16-19 Months of age) and Mth 23 (24-27 Months of age). *Data presented included only results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by PCR assay	up to study end at Month 23 (24-27 months of age)
Secondary	Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).	Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.	During the 4-day (Days 0-3) post-primary vaccination period across doses
Secondary	Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).	General AEs = diarrhoea, drowsiness, irritability, loss of appetite, vomiting and fever (axillary = 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. diarrhoea: = 6 looser than normal stools/day. vomiting: = 3 episodes of vomiting/day. Fever = > 39.5°C Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Days 0-3) post-primary vaccination period across doses
Secondary	Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).	Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.	During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine
Secondary	Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).	Solicited general AEs = drowsiness, irritability, loss of appetite and fever (axillary = 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. Fever = temperature > 39.5°C Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine
Secondary	Number of Subjects With Unsolicited AEs.	An unsolicited adverse event is any adverse event (i.e. any 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) 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.	Within the 31-day (Days 0-30) post-primary vaccination period
Secondary	Number of Subjects With Unsolicited AEs.	An unsolicited adverse event is any adverse event (i.e. any 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) 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.	Within the 31-day (Days 0-30) post Synflorix booster vaccination period
Secondary	Number of Subjects With Serious Adverse Events (SAEs).	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.	From study start at Month 0 (6 weeks of age and above) up to study end at Month 23 (24-27 months of age)

External 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.