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

December 6, 2019 updated by: Shabir Madhi, University of Witwatersrand, South Africa

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • GP
      • Soweto, GP, South Africa, 2055
        • Nrf/Dst Vpd Rmpru
    • Gauteng
      • Johannesburg, Gauteng, South Africa
        • Chris Hani Baragwanath Academic hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 2 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Prevenar 13

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 month post booster vaccine

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)..
9 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Witwatersrand, South Africa

Collaborators

University College, London

Investigators

  • Principal Investigator: Shabir A Madhi, MD, PhD, University of Witwatersrand, South Africa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 9, 2017

Primary Completion (Actual)

February 26, 2019

Study Completion (Actual)

February 26, 2019

Study Registration Dates

First Submitted

October 21, 2016

First Submitted That Met QC Criteria

October 21, 2016

First Posted (Estimate)

October 25, 2016

Study Record Updates

Last Update Posted (Actual)

December 9, 2019

Last Update Submitted That Met QC Criteria

December 6, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCV1+1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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