Clinical trial NCT04275284: Persistence of Immunogenicity Following Reduced PCV Dosing Schedules in South African Children
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia
Meningitis
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
First posted: 2020-02-19
Enrollment: 600
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serotype specific geometric mean antibody concentrations (GMC)
timeFrame: 3, 4 and 5 years of age
Secondary outcomes:
measure: Modified threshold of protection
timeFrame: 3, 4 and 5 years of age
measure: Comparison between 6-week and 14-week primary dose
timeFrame: 3, 4 and 5 years of age
measure: Colonization outcome
timeFrame: 3, 4 and 5 years of age
Other outcomes:
Locations:
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU
state: Gauteng
Study officials:
affiliation: University of the Witwatersrand, South Africa
name: Shabir A Madhi, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: