Persistence of Immunogenicity Following Reduced PCV Dosing Schedules in South African Children

Completed

• Conditions: Meningitis; Pneumonia

• Registration Number: NCT04275284
• Lead Sponsor: University of Witwatersrand, South Africa

Brief Summary

This study will evaluate the persistence of immunogenicity following a reduced dosing schedule of 10- or 13-valent Pneumococcal Conjugate Vaccine (PCV10, PCV13). This is the follow-up of a randomized controlled trial in which children received a single priming dose of PCV10 or PCV13 (at 6 or 14 weeks of age) followed by booster dose at 9 months of age (1+1 schedule), compared to a 2+1 PCV schedule (6, 14 weeks of age and 9 months of age).

Detailed Description

Between 2017 and 2019, we conducted an open-labelled, randomized controlled trial to evaluate for non-inferiority in the post-booster serotype-specific geometric mean concentrations (GMC's) in children randomized to receive either PCV10 or PCV13 as a 1+1 schedule (with the first dose occurring either at 6 or 14 weeks of age) compared to infants who received a two dose primary series (6 and 14 weeks of age). All six study groups received a booster dose at 40 weeks of age, and serotype-specific IgG and opsonophagocytic activity was measured one-month post booster. Subjects were planned to be followed-up until 18 months of age as part of the initial study. In the present study, we propose to extent the follow-up of the cohort to include annual visit at 3, 4 and 5 years of age, to evaluate the sustainability of the humoral immune response of the different PCV dosing schedules.

Study Timeline

• Study Start: 2020-02-14
• Study First Submitted: 2020-02-14
• Study First Submitted QC: 2020-02-14
• Study First Posted: 2020-02-19
• Primary Completion: 2022-12-01
• Study Completion: 2022-12-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-20
• Last Update Posted: 2024-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Children between and including the ages of 36 - 38 months of age at the time of first blood sampling;
2. Subjects who previously participated in the PCV1+1 study and received the full study vaccination regime as per protocol;
3. The parent or legal guardian of the child must be able and willing to provide written informed consent for all 3 visits and comply with all study requirements;
4. The parent or legal guardian of the child must indicate the intention to remain in the study area for the duration of the trial - or be willing to bring the child for all visits.

Exclusion Criteria

1. Receipt of any additional pneumococcal vaccine since the end of participation in the PCV1+1 study;
2. Any known or suspected immunodeficiency condition which could affect immune response to vaccination, including living with HIV;
3. Receipt of any immunoglobulins and/or blood products less than 6 months prior to blood sampling;
4. Parent/legal guardian unable or unwilling to attend scheduled study visits.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Serotype specific geometric mean antibody concentrations (GMC)	3, 4 and 5 years of age	To evaluate persistence of vaccine-serotype specific GMCs at 3, 4 and 5 years of age between children receiving differing 1+1 dosing schedules compared to the 2+1 dosing schedule of the same vaccine formulation (i.e. PCV10 or PCV13).

Secondary Outcome Measures

Name	Time	Method
Comparison between 6-week and 14-week primary dose	3, 4 and 5 years of age	To evaluate persistence of vaccine-serotype specific serum IgG antibody concentration above the WHO-defined putative threshold for protection (≥0.35 µg/mL), the modified serotype-specific correlate of protection against IPD as proposed by Andrews et al. (17) and GMC's at 3, 4 and 5 years in children receiving the 1+1 dosing schedule at either 6 weeks of age compared to those who received it at 14 weeks of age, stratified for the individual vaccine formulation (PCV10 and PCV13).
Colonization outcome	3, 4 and 5 years of age	To compare the prevalence of vaccine-serotype (stratified by PCV10 and PCV13 serotypes)
Modified threshold of protection	3, 4 and 5 years of age	To evaluate persistence of vaccine-serotype specific serum IgG antibody concentration above the WHO-defined putative threshold for protection (≥0.35 µg/mL) and the modified serotype-specific correlate of protection against IPD as proposed by Andrews et al.(17) at 3, 4 and 5 years of between children with differing 1+1 dosing schedules compared to the 2+1 dosing schedule of the same vaccine formulation

Trial Locations

Locations (1)

Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU; 🇿🇦 Soweto, Gauteng, South Africa