Reduced PCV Dosing Schedules in South African Infants

NCT ID: NCT02943902

Last Updated: 2019-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-09
• Study Completion Date: 2019-02-26

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).

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.

Conditions

Pneumonia; Meningitis

Keywords

immunogenicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1a (1+1, 6 weeks)

PCV10 (Synflorix 0.5ml injection) will be administered at 6 weeks and 9 months of age

Group Type: EXPERIMENTAL

Pneumococcal conjugate vaccine (PCV10 ) 1+1, 6 weeks

Intervention Type: BIOLOGICAL

PCV10 1+1, 6 weeks \& 9 months

Group 1b (1+1, 6 weeks)

PCV13 (Prevenar 13, 0.5ml injection) will be administered at 6 weeks and 9 months of age

Group Type: EXPERIMENTAL

Pneumococcal conjugate vaccine (PCV13 ) 1+1, 6 weeks

Intervention Type: BIOLOGICAL

PCV13 1+1, 6 weeks \& 9 months

Group 2a (1+1, 14 weeks)

PCV10 (Synflorix 0.5ml injection) will be administered at 14 weeks and 9 months of age

Group Type: EXPERIMENTAL

Pneumococcal conjugate vaccine (PCV10 ) 1+1, 14 weeks

Intervention Type: BIOLOGICAL

PCV10 1+1, 14 weeks \& 9 months

Group 2b (1+1, 14 weeks)

PCV13 (Prevenar 13, 0.5ml injection) will be administered at 14 weeks and 9 months of age

Group Type: EXPERIMENTAL

Pneumococcal conjugate vaccine (PCV13 ) 1+1, 14 weeks

Intervention Type: BIOLOGICAL

PCV13 1+1, 14 weeks \& 9 months

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

Group Type: ACTIVE_COMPARATOR

Pneumococcal conjugate vaccine (PCV10 ) 2+1

Intervention Type: BIOLOGICAL

PCV10 2+1, 6\&14 weeks \& 9 months

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

Group Type: ACTIVE_COMPARATOR

Pneumococcal conjugate vaccine (PCV13 ) 2+1

Intervention Type: BIOLOGICAL

PCV13 2+1, 6\&14 weeks \& 9 months

Interventions

Pneumococcal conjugate vaccine (PCV10 ) 1+1, 6 weeks

PCV10 1+1, 6 weeks \& 9 months

Intervention Type: BIOLOGICAL

Pneumococcal conjugate vaccine (PCV10 ) 1+1, 14 weeks

PCV10 1+1, 14 weeks \& 9 months

Intervention Type: BIOLOGICAL

Pneumococcal conjugate vaccine (PCV10 ) 2+1

PCV10 2+1, 6\&14 weeks \& 9 months

Intervention Type: BIOLOGICAL

Pneumococcal conjugate vaccine (PCV13 ) 1+1, 6 weeks

PCV13 1+1, 6 weeks \& 9 months

Intervention Type: BIOLOGICAL

Pneumococcal conjugate vaccine (PCV13 ) 1+1, 14 weeks

PCV13 1+1, 14 weeks \& 9 months

Intervention Type: BIOLOGICAL

Pneumococcal conjugate vaccine (PCV13 ) 2+1

PCV13 2+1, 6\&14 weeks \& 9 months

Intervention Type: BIOLOGICAL

Other Intervention Names

Synflorix (PCV10); Synflorix (PCV10); Synflorix (PCV10); Prevenar 13; Prevenar 13; Prevenar 13

Eligibility 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.

• Minimum Eligible Age: 5 Weeks
• Maximum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University College, London

OTHER

Sponsor Role: collaborator

University of Witwatersrand, South Africa

OTHER

Sponsor Role: lead

Responsible Party

Shabir Madhi

Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shabir A Madhi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Witwatersrand, South Africa

Locations

Chris Hani Baragwanath Academic Hospital

Johannesburg, Gauteng, South Africa

Nrf/Dst Vpd Rmpru

Soweto, GP, South Africa

Countries

South Africa

References

Izu A, Mutsaerts EA, Olwagen C, Jose L, Koen A, Nana AJ, Cutland CL, Madhi SA. Serotype-specific serum immunoglobulin G at 18 months of age following one or two doses of a primary series of 10-valent or 13-valent pneumococcal conjugate vaccine and a booster dose at nine months of age: a randomized controlled study. Expert Rev Vaccines. 2025 Dec;24(1):121-127. doi: 10.1080/14760584.2025.2458179. Epub 2025 Jan 27.

Reference Type: DERIVED

PMID: 39865559 (View on PubMed)

Mutsaerts EAML, van Cranenbroek B, Madhi SA, Simonetti E, Arns AJ, Jose L, Koen A, van Herwaarden AE, de Jonge MI, Verhagen LM. Impact of nutritional status on vaccine-induced immunity in children living in South Africa: Investigating the B-cell repertoire and metabolic hormones. Vaccine. 2024 May 22;42(14):3337-3345. doi: 10.1016/j.vaccine.2024.04.034. Epub 2024 Apr 17.

Reference Type: DERIVED

PMID: 38637212 (View on PubMed)

Olwagen CP, Izu A, Mutsaerts EAML, Jose L, Koen A, Downs SL, Van Der Merwe L, Laubscher M, Nana AJ, Moultrie A, Cutland CL, Dorfman JR, Madhi SA. Single priming and booster dose of ten-valent and 13-valent pneumococcal conjugate vaccines and Streptococcus pneumoniae colonisation in children in South Africa: a single-centre, open-label, randomised trial. Lancet Child Adolesc Health. 2023 May;7(5):326-335. doi: 10.1016/S2352-4642(23)00025-1. Epub 2023 Mar 16.

Reference Type: DERIVED

PMID: 36934731 (View on PubMed)

Madhi SA, Mutsaerts EA, Izu A, Boyce W, Bhikha S, Ikulinda BT, Jose L, Koen A, Nana AJ, Moultrie A, Roalfe L, Hunt A, Goldblatt D, Cutland CL, Dorfman JR. Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2020 Dec;20(12):1426-1436. doi: 10.1016/S1473-3099(20)30289-9. Epub 2020 Aug 25.

Reference Type: DERIVED

PMID: 32857992 (View on PubMed)

Other Identifiers

PCV1+1

Identifier Type: -

Identifier Source: org_study_id