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Reduced PCV Dosing Schedules in South African Infants (PCV1+1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02943902
Recruitment Status : Completed
First Posted : October 25, 2016
Last Update Posted : December 9, 2019
Sponsor:
Collaborator:
University College, London
Information provided by (Responsible Party):
Shabir Madhi, University of Witwatersrand, South Africa

Brief Summary:
This study will evaluate the immunogenicity of a reduced dosing schedule of Pneumococcal Conjugate vaccine (PCV) PCV10 and PCV13, in which children will receive a primary dose at either 6 or 14 weeks of age, followed by a booster dose at 9 months of age (1+1 schedule), and compare this immune response to those who receive a two dose primary series (at 6 and 14 weeks of age) and booster dose at 9-months (2+1 schedule).

Condition or disease Intervention/treatment Phase
Pneumonia Meningitis Biological: Pneumococcal conjugate vaccine (PCV10 ) 1+1, 6 weeks Biological: Pneumococcal conjugate vaccine (PCV10 ) 1+1, 14 weeks Biological: Pneumococcal conjugate vaccine (PCV10 ) 2+1 Biological: Pneumococcal conjugate vaccine (PCV13 ) 1+1, 6 weeks Biological: Pneumococcal conjugate vaccine (PCV13 ) 1+1, 14 weeks Biological: Pneumococcal conjugate vaccine (PCV13 ) 2+1 Phase 3

Detailed Description:

Pneumonia is the leading global cause of childhood death outside of the neonatal period, and contributes to 19% of the 10 million childhood deaths occurring annually, the majority of which occurs in industrialising countries. Despite the successes in improving primary healthcare in South Africa since 1994, pneumonia nevertheless remains a leading cause of childhood death in South Africa, aggravated by the HIV/AIDS epidemic. Streptococcus pneumoniae is recognised as the leading bacterial cause of pneumonia in children as well as having been identified as a common cause of super-imposed bacterial infection in individuals with respiratory virus-associated pneumonia.

In South Africa, the cost of procurement of PCV ($20 per dose) totals almost 50% of the total cost of all vaccines purchased for the national immunisation program. Similarly, PCV is the most expensive vaccine purchased by the Global Alliance for Vaccines and Immunisation (GAVI), which heavily funds vaccine procurement for low income countries. The sustainability of continued procurement of this vaccine at the current pricing in low-middle income countries remains uncertain.

This will be a randomized, open-label study (laboratory personnel will however be blinded) in which subjects are randomized to one of two (primary dose at either 6 or 14 weeks of age) 1+1 dosing schedules of PCV10 or PCV13, or to a 2+1 schedule of these vaccines. A total of 600 subjects will be randomized in a 1:1:1:1:1:1 ratio to one of the six groups. The study will be undertaken at an experienced research site in Johannesburg, South Africa, where the 600 children born to HIV-uninfected women are expected to be enrolled over a 12- month period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: An Open-labeled, Randomized Controlled Trial Evaluating for Non-inferiority of 1+1 Compared to 2+1 Dosing Schedules of 10-valent and 13-valent Pneumococcal Conjugate Vaccine (PCV) in South African Children
Actual Study Start Date : January 9, 2017
Actual Primary Completion Date : February 26, 2019
Actual Study Completion Date : February 26, 2019


Arm Intervention/treatment
Experimental: Group 1a (1+1, 6 weeks)
PCV10 (Synflorix 0.5ml injection) will be administered at 6 weeks and 9 months of age
Biological: Pneumococcal conjugate vaccine (PCV10 ) 1+1, 6 weeks
PCV10 1+1, 6 weeks & 9 months
Other Name: Synflorix (PCV10)

Experimental: Group 1b (1+1, 6 weeks)
PCV13 (Prevenar 13, 0.5ml injection) will be administered at 6 weeks and 9 months of age
Biological: Pneumococcal conjugate vaccine (PCV13 ) 1+1, 6 weeks
PCV13 1+1, 6 weeks & 9 months
Other Name: Prevenar 13

Experimental: Group 2a (1+1, 14 weeks)
PCV10 (Synflorix 0.5ml injection) will be administered at 14 weeks and 9 months of age
Biological: Pneumococcal conjugate vaccine (PCV10 ) 1+1, 14 weeks
PCV10 1+1, 14 weeks & 9 months
Other Name: Synflorix (PCV10)

Experimental: Group 2b (1+1, 14 weeks)
PCV13 (Prevenar 13, 0.5ml injection) will be administered at 14 weeks and 9 months of age
Biological: Pneumococcal conjugate vaccine (PCV13 ) 1+1, 14 weeks
PCV13 1+1, 14 weeks & 9 months
Other Name: Prevenar 13

Active Comparator: Group 3a (2+1)
PCV10 (Synflorix 0.5ml injection) will be administered at 6 weeks, 14 weeks and 9 months of age, as per EPI schedule in South Africa
Biological: Pneumococcal conjugate vaccine (PCV10 ) 2+1
PCV10 2+1, 6&14 weeks & 9 months
Other Name: Synflorix (PCV10)

Active Comparator: Group 3b (2+1)
PCV13 (Prevenar 13, 0.5ml injection) will be administered at 6 weeks, 14 weeks and 9 months of age, as per EPI schedule in South Africa
Biological: Pneumococcal conjugate vaccine (PCV13 ) 2+1
PCV13 2+1, 6&14 weeks & 9 months
Other Name: Prevenar 13




Primary Outcome Measures :
  1. serotype specific geometric mean antibody concentrations (GMC) one month following the booster dose [ Time Frame: 1 month post booster vaccine ]
    The serotype-specific GMC measured 1 month after the 9-month booster dose for each 1+1 vaccine group and comparing it to the 2+1 group of the same vaccine


Secondary Outcome Measures :
  1. Immunogenicity: percentage of children with vaccine-serotype specific serum IgG antibody concentration above the WHO-defined putative threshold for protection (≥0.35 µg/mL) at 9 months of age, prior to the booster dose of differing 1+1 dosing schedules [ Time Frame: 9 months of age ]
    1. To evaluate the percentage of children with vaccine-serotype specific serum IgG antibody concentration above the WHO-defined putative threshold for protection (≥0.35 µg/mL) at 9 months of age, prior to the booster dose of differing 1+1 dosing schedules (i.e. primary dose given at either 6 or 14 weeks of age) compared to that of children who received a 2 dose primary series (i.e. 2+1 dosing schedule group)..



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Weeks to 18 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Signed informed consent by the parent/guardian of the child;
  2. Born to an HIV-uninfected women, based on testing undertaken as part of standard of care during the last trimester of pregnancy;
  3. Had not received any vaccine other than BCG and OPV (routinely given at birth) prior to enrolment;
  4. Birth weight >2499g AND weight of child >3.5 kg at time of proposed randomization;
  5. Aged 42-56 days of age at time of enrolment;
  6. Available for the duration of the study;
  7. Child is healthy based on medical history and physical examination of the study-staff.

Exclusion Criteria:

  1. Any clinically significant major congenital abnormalities;
  2. Previous hospitalization for a respiratory illness following discharge from hospital after birth;
  3. Receipt of any other investigational drug/vaccine. Co-enrollment into non-investigational studies, including epidemiology studies, is allowed;
  4. Any previous PCV vaccination;
  5. Known allergy to any of the vaccine components;
  6. Febrile illness (axillary temperature ≥37.8°C) at time of enrolment. These participants are eligible if the temperature resolves for at least 48 hours and they remain within the study defined window periods;
  7. Planned relocation to outside of the study area during up until age of 2 years;
  8. Receipt of blood transfusion or any other blood products (including immunoglobulins) since birth. Receipt of such products during the course of the study, will require withdrawal of the child from the study;
  9. History of confirmed pneumococcal disease since birth;
  10. Any known or suspected immunodeficiency condition which could affect immune response to vaccination.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02943902


Locations
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South Africa
Chris Hani Baragwanath Academic Hospital
Johannesburg, Gauteng, South Africa
Nrf/Dst Vpd Rmpru
Soweto, GP, South Africa, 2055
Sponsors and Collaborators
University of Witwatersrand, South Africa
University College, London
Investigators
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Principal Investigator: Shabir A Madhi, MD, PhD University of Witwatersrand, South Africa
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Shabir Madhi, Investigator, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT02943902    
Other Study ID Numbers: PCV1+1
First Posted: October 25, 2016    Key Record Dates
Last Update Posted: December 9, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data will be made publically available, within one year of completion of the study to any investigators or BMGF nominated partners, who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to
Keywords provided by Shabir Madhi, University of Witwatersrand, South Africa:
immunogenicity
Additional relevant MeSH terms:
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Pneumonia
Meningitis
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Central Nervous System Diseases
Nervous System Diseases
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs