Persistence of Immunogenicity Following Reduced PCV Dosing Schedules in South African Children (PCV1+1_FU)

Evaluation of Persistence of Immunogenicity Following an Open-labelled, Randomized Controlled Trial Evaluating Non-inferiority of 1+1 Compared to 2+1 Dosing Schedules of 10-valent and 13-valent Pneumococcal Conjugate Vaccine in South Africa

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).

Study Overview

• Status: Completed
• Conditions: Pneumonia; Meningitis
• Intervention / Treatment: Biological: PCV10; Biological: PCV13

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 Type: Observational
• Enrollment (Actual): 600

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All participants who completed the PCV1+1 study and received all vaccines as specified per study protocol will be contacted to participate.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PCV10 1+1, 6 weeks & 9 months; Follow-up of children who were previously randomized to PCV10 (Synflorix 0.5ml injection) administered at 6 weeks and 9 months of age.	Biological: PCV10; 0.5 ml injection; Other Names: Synflorix
PCV13 1+1, 6 weeks & 9 months; Follow-up of children who were previously randomized to PCV13 (Prevnar 13, 0.5ml injection) administered at 6 weeks and 9 months of age.	Biological: PCV13; 0.5 ml injection; Other Names: Prevnar13
PCV10 1+1, 14 weeks & 9 months; Follow-up of children who were previously randomized to PCV10 (Synflorix 0.5ml injection) administered at 14 weeks and 9 months of age.	Biological: PCV10; 0.5 ml injection; Other Names: Synflorix
PCV13 1+1, 14 weeks & 9 months; Follow-up of children who were previously randomized to PCV13 (Prevnar 13, 0.5ml injection) administered at 14 weeks and 9 months of age.	Biological: PCV13; 0.5 ml injection; Other Names: Prevnar13
PCV10 2+1, 6&14 weeks & 9 months; Follow-up of children who were previously randomized to PCV10 (Synflorix 0.5ml injection) administered at 6 weeks, 14 weeks and 9 months of age.	Biological: PCV10; 0.5 ml injection; Other Names: Synflorix
PCV13 2+1, 6&14 weeks & 9 months; Follow-up of children who were previously randomized to PCV13 (Prevnar 13, 0.5ml injection) administered at 6 weeks, 14 weeks and 9 months of age.	Biological: PCV13; 0.5 ml injection; Other Names: Prevnar13

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype specific geometric mean antibody concentrations (GMC)	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).	3, 4 and 5 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified threshold of protection	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	3, 4 and 5 years of age
Comparison between 6-week and 14-week primary dose	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).	3, 4 and 5 years of age
Colonization outcome	To compare the prevalence of vaccine-serotype (stratified by PCV10 and PCV13 serotypes)	3, 4 and 5 years of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonization outcome	To compare the prevalence of vaccine-serotype (stratified by PCV10 and PCV13 serotypes) and non-vaccine serotype nasopharyngeal colonization at 3, 4 and 5 years of age for the 1+1 dosing schedule groups compared to the 2+1 groups.	3, 4 and 5 years of age

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuroinflammatory Diseases; Meningitis; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: PCV1+1 follow-up

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No