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

Pneumonia Clinical Trial

— PCV1+1_FU  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04275284
• Other study ID #: PCV1+1 follow-up
• Status: Completed
• Start date: February 14, 2020
• Est. completion date: December 1, 2022

Study information

• Verified date: February 2020
• Source: University of Witwatersrand, South Africa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Gender: All
• Age group: 3 Years to 5 Years

Eligibility

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.

Related Conditions & MeSH terms

• Meningitis
• Pneumonia

Intervention

Biological:
• PCV10
0.5 ml injection
• PCV13
0.5 ml injection

Locations

Country	Name	City	State
South Africa	Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU	Soweto	Gauteng

Sponsors (1)

Lead Sponsor	Collaborator
University of Witwatersrand, South Africa

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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