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.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00829010
First received: January 22, 2009
Last updated: March 13, 2014
Last verified: February 2014
Results First Received: May 8, 2012  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Infections, Streptococcal
Interventions: Biological: Pneumococcal vaccine GSK1024850A
Biological: Tritanrix-HepB/Hib
Biological: measles
Biological: Rotarix
Biological: Local OPV

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The oral poliovirus vaccine could be given at any time during the study (routinely given concurrently with Tritanrix™-HepB/Hib vaccine) but was not considered as study vaccine.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

The study included 3 populations defined based on the human immunodeficiency virus status of the mother and the infant. Infant born from:

  • a HIV positive mother and HIV infected at Month 0 = HIV+/+.
  • a HIV positive mother and HIV exposed uninfected at screening = HIV+/-.
  • a HIV negative mother and HIV unexposed uninfected at Month 0 = HIV-

Reporting Groups
  Description
HIV+/+ Group Infants born from a HIV positive mother and confirmed as HIV infected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered intramuscularly in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid r
HIV+/- Group Infants born from a HIV positive mother and confirmed as HIV exposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (3+1) Group Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (EPI) Group Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 3 primary doses of Synflorix™ vaccine (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (2+1) Group Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 2 primary doses (at 6 & 14 weeks of age at study Months 0 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Participant Flow:   Overall Study
    HIV+/+ Group     HIV+/- Group     HIV- (3+1) Group     HIV- (EPI) Group     HIV- (2+1) Group  
STARTED     87     97     100     100     100  
COMPLETED     81     92     98     94     98  
NOT COMPLETED     6     5     2     6     2  
Adverse Event                 6                 3                 0                 3                 0  
Withdrawal by Subject                 0                 0                 1                 0                 2  
Lost to Follow-up                 0                 1                 1                 3                 0  
Unspecified                 0                 1                 0                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
HIV+/+ Group Infants born from a HIV positive mother and confirmed as HIV infected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered intramuscularly in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV+/- Group Infants born from a HIV positive mother and confirmed as HIV exposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (3+1) Group Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (EPI) Group Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 3 primary doses of Synflorix™ vaccine (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (2+1) Group Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 2 primary doses (at 6 & 14 weeks of age at study Months 0 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
Total Total of all reporting groups

Baseline Measures
    HIV+/+ Group     HIV+/- Group     HIV- (3+1) Group     HIV- (EPI) Group     HIV- (2+1) Group     Total  
Number of Participants  
[units: participants]
  87     97     100     100     100     484  
Age  
[units: Weeks]
Mean ± Standard Deviation
  6.6  ± 0.92     6.3  ± 0.64     6.1  ± 0.41     6.1  ± 0.35     6.1  ± 0.29     6.2  ± 0.52  
Gender  
[units: Subjects]
           
Female     50     46     58     50     47     251  
Male     37     51     42     50     53     233  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL).   [ Time Frame: 1 month following primary immunization (post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, HIV- (EPI) Group and post-Dose 2 at Month 3 for the HIV- (2+1) Group) ]

2.  Secondary:   Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

3.  Secondary:   Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

4.  Secondary:   Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

5.  Secondary:   Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

6.  Secondary:   Concentrations of Antibodies Against Protein D (PD) by Enzyme Linked ImmunoSorbent Assay (ELISA).   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

7.  Secondary:   Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).   [ Time Frame: 1 month following primary immunization (at Month 3) ]

8.  Secondary:   Concentrations of Antibodies Against Bordetella Pertussis (BP) by Enzyme Linked ImmunoSorbent Assay (ELISA).   [ Time Frame: 1 month following primary immunization (at Month 3) ]

9.  Secondary:   Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)   [ Time Frame: 1 month following primary immunization (at Month 3) ]

10.  Secondary:   Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA).   [ Time Frame: 1 month following primary immunization (at Month 3) ]

11.  Secondary:   Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.   [ Time Frame: 1 month after the administration of the second vaccine dose (at Month 3) ]

12.  Secondary:   Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) post-primary vaccination period ]

13.  Secondary:   Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) post-primary vaccination period ]

14.  Secondary:   Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine ]

15.  Secondary:   Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine ]

16.  Secondary:   Number of Subjects With Unsolicited AEs.   [ Time Frame: Within the 31-day (Days 0-30) post-primary vaccination period ]

17.  Secondary:   Number of Subjects With Unsolicited AEs.   [ Time Frame: Within the 31-day (Days 0-30) post Synflorix booster vaccination period ]

18.  Secondary:   Number of Subjects With Serious Adverse Events (SAEs).   [ Time Frame: From study start (at Month 0) up to 1 month after Synflorix booster vaccination (up to Month 9) ]

19.  Secondary:   Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

20.  Secondary:   Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

21.  Secondary:   Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

22.  Secondary:   Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

23.  Secondary:   Concentrations of Antibodies Against Protein D (PD) by Enzyme-Linked ImmunoSorbent Assay (ELISA).   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

24.  Secondary:   Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

25.  Secondary:   Concentrations of Antibodies Against Bordetella Pertussis (BP) by Enzyme-Linked ImmunoSorbent Assay (ELISA).   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

26.  Secondary:   Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

27.  Secondary:   Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs)by Enzyme-Linked ImmunoSorbent Assay (ELISA).   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

28.  Secondary:   Titers of Antibodies Against Measles   [ Time Frame: 1 month following administration of the 1st and 2nd vaccine dose (at Months 9 and 15) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

29.  Secondary:   Salivary Antibodies Against Selected Common Bacterial Protein Antigens.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

30.  Secondary:   Prevalence of Haemophilus Influenzae and/or Streptococcus Pneumoniae (Vaccine Serotypes, Cross-reactive or Other Serotypes) and Other Bacterial Pathogens in the Nasopharynx.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

31.  Secondary:   Acquisition of New S. Pneumoniae and/or H. Influenzae Strains.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No

32.  Secondary:   Number of Subjects With Serious Adverse Events (SAEs).   [ Time Frame: From study start at Month 0 (6 weeks of age and above) up to study end at Month 23 (24-27 months of age) ]
Results not yet posted.   Anticipated Posting Date:   08/2014   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study aimed to enrol 100 HIV +/+ subjects but only succeed to enrol 87 mainly due to the decrease of vertical HIV transmission in South Africa


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Koen A et al. Immunogenicity of oral live attenuated human rotavirus vaccine given as two doses (10 and 14 weeks) in HIV‐infected, HIV‐exposed‐uninfected and HIV‐unexposed‐uninfected infants in South Africa. Abstract presented at the 19th International AIDS Conference (IAC), Washington DC, USA, 22‐27 July 2012.
Mahdi S et al. Vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine [PHiD-CV] according to different schedules in healthy South African children. Abstract presented at the 30th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), Thessaloniki, Greece, 8-12 May 2012.


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00829010     History of Changes
Other Study ID Numbers: 111634
Study First Received: January 22, 2009
Results First Received: May 8, 2012
Last Updated: March 13, 2014
Health Authority: South Africa: Medicines Control Council