Clinical trial NCT00829010: 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.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Human Immunodeficiency Virus
Booster vaccination
Safety
Primary vaccination
Pneumococcal vaccine
Immunogenicity
Pneumococcal disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-01-26
Enrollment: 489
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL).
timeFrame: 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 outcomes:
measure: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.
timeFrame: At Month 3 and Month 9
measure: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.
timeFrame: At Month 3 and at Month 9
measure: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.
timeFrame: At Month 3 and Month 9
measure: Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.
timeFrame: At Month 3 and at Month 9
measure: Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Concentrations of Antibodies Against Protein D (PD) by ELISA
timeFrame: At Month 3 and at Month 9
measure: Concentrations of Antibodies Against Protein D (PD) by ELISA.
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).
timeFrame: 1 month following primary immunization (at Month 3)
measure: Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).
timeFrame: 1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)
measure: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA.
timeFrame: 1 month following primary immunization (at Month 3)
measure: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA .
timeFrame: 1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)
measure: Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)
timeFrame: 1 month following primary immunization (at Month 3)
measure: Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)
timeFrame: 1 month after the booster vaccination (at Month 15)
measure: Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA
timeFrame: 1 month following primary immunization (at Month 3)
measure: Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA.
timeFrame: 1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)
measure: Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.
timeFrame: 1 month after the administration of the second vaccine dose (at Month 3)
measure: Concentrations of Antibodies Against Measles
timeFrame: 1 month following administration of the 1st and 2nd vaccine dose (at Months 9 and 15)
measure: Anti-LytC IgA and Anti-PhtD IgA Antibodies Concentrations in Salivary Samples
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: 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.
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs
timeFrame: up to study end at Month 23 (24-27 months of age)
measure: Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).
timeFrame: During the 4-day (Days 0-3) post-primary vaccination period across doses
measure: Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).
timeFrame: During the 4-day (Days 0-3) post-primary vaccination period across doses
measure: Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).
timeFrame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine
measure: Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).
timeFrame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine
measure: Number of Subjects With Unsolicited AEs.
timeFrame: Within the 31-day (Days 0-30) post-primary vaccination period
measure: Number of Subjects With Unsolicited AEs.
timeFrame: Within the 31-day (Days 0-30) post Synflorix booster vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From study start at Month 0 (6 weeks of age and above) up to study end at Month 23 (24-27 months of age)
Other outcomes:
Locations:
city: Soweto
country: South Africa
facility: GSK Investigational Site
state: Gauteng
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Nunes MC, Moreira M, Koen A, van Niekerk N, Jose L, Cutland CL, Francois N, Schoonbroodt S, Ruiz-Guinazu J, Yarzabal JP, Borys D, Schuerman L, Madhi SA. Bacterial nasopharyngeal carriage following infant immunization with pneumococcal conjugate vaccines according to a 2+1 schedule in children in South Africa: an exploratory analysis of two clinical trials. Expert Rev Vaccines. 2020 Dec;19(12):1177-1189. doi: 10.1080/14760584.2020.1853533. Epub 2020 Dec 21.
citation: Madhi SA, Moreira M, Koen A, van Niekerk N, de Gouveia L, Jose L, Cutland CL, Francois N, Schoonbroodt S, Ruiz-Guinazu J, Yarzabal JP, Borys D, Schuerman L. Impact of HIV status and vaccination schedule on bacterial nasopharyngeal carriage following infant immunisation with the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in South Africa. Vaccine. 2020 Feb 28;38(10):2350-2360. doi: 10.1016/j.vaccine.2020.01.062. Epub 2020 Feb 5.
citation: Madhi SA, Koen A, Jose L, Moreira M, van Niekerk N, Cutland C, Francois N, Ruiz-Guinazu J, Yarzabal JP, Borys D, Schuerman L. Immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) according to different schedules in infants in South Africa: a phase III trial. Expert Rev Vaccines. 2017 Jun;16(6):641-656. doi: 10.1080/14760584.2017.1321990.
citation: Madhi SA, Koen A, Jose L, van Niekerk N, Adrian PV, Cutland C, Francois N, Ruiz-Guinazu J, Yarzabal JP, Moreira M, Borys D, Schuerman L. Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status. Medicine (Baltimore). 2017 Jan;96(2):e5881. doi: 10.1097/MD.0000000000005881.