Clinical trial NCT04102137: 3-year Follow-up After a Single Dose Acellular Pertussis Vaccination
Official title: Antibody Persistence at 3 Years After a Single Dose Vaccination of Acellular Pertussis Vaccines Containing Genetically-detoxified Pertussis Toxin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pertussis
Keywords: TDA202
acellular pertussis vaccine
antibody persistence at 3 years after vaccination
Pertagen
Boostagen
aP vaccine
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2019-09-25
Enrollment: 181
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population for this study is the group of subjects who had received one dose of acellular pertussis based vaccine in TDA202 trial at Vaccine Trial Centre (VTC), Faculty of Tropical Medicine, Mahidol University and who had completed the study follow-up at 1 year after vaccination.

Brief summary: In July 2015-November 2016, a phase II/III randomized, observer-blind,controlled study of two acellular Pertussis vaccines (aP standalone and TdaP combined vaccined) manufactured by BioNet-Asia Co., Ltd. (Bionet) and chemically-detoxified Adacel Tdap vaccine was conducted in Bangkok, Thailand in healthy subjects aged 12-17 years (Protocol No. TDA202; http://clinicaltrials.in.th;Study ID:TCTR20150703002). A total of 450 subjects were enrolled into the study at 2 study sites (Site No.1:Faculty of Medicine Siriraj Hospital; Site No.2:Vaccine Trial Centre (VTC), Faculty of Tropical Medicine, Mahidol University) with equal number of 225 subjects enrolled at each study site. During the study, the subjects had been randomized in a 1:1:1 ratio to received intramuscularly a booster dose (0.5 mL) of the study vaccines.

This is further follow-up from TDA202 clinical trial, which was completed on 29 November 2016. Target population for this study is the group of subjects who had received one dose of one of the three study vaccines in the TDA202 trial at site VTC and who had completed the study follow-up at 1-year after vaccination (223 subjects).

In this current study, the long-term persistence of pertussis antibodies induced by a booster dose of recombinant acellular Pertussis based vaccines (Pertagen and Boostagen) manufactured by Bionet will be evaluated and compared to the conventional chemically-detoxified Tdap vaccine (Adacel) at 3 years after previously immunized in the TDA202 study.

Detailed description: The study population will included all subjects who participated in the TDA202 study at the Vaccine Trial Centre (VTC), Faculty of Tropical Medicine, Mahidol University, Bangkok.

The subjects who had received a single dose of one of the 3 study vaccines and completed 1-year follow-up visit at Day 336±28 during the TDA202 study will be called in for consent process at 3 years after vaccination based on Vaccination Date in TDA202 study within ±1 month window period. Subjects aged ≥ 18 years who have signed the written informed consent form or subjects aged \< 18 years who have signed the assent form with their parent/legal guardian's given written informed consent will be screened for general health status and those who fulfill all inclusion and exclusion criteria will be enrolled into the study.

Once enrolled, blood sample (approximately 5 mL) will be taken from all subjects. After blood collection, vaccination with a licensed influenza vaccine will be offered to all subjects.Blood samples will be processed for serum separation and shipped to Bionet Human Serology Laboratory where immunogenicity testing (ELISA antibodies against tetanus (TT), diphtheria(DT), Pertussis Toxin (PT) and Filamentous hemagglutinin (FHA) and PT neutralizing antibody by Chinese Hamster Ovary (CHO cell assay) will be performed . ELISA testing to detect antibodies against tetanus, diphtheria, and pertussis antigens (PT and FHA) will be performed for all enrolled subjects while CHO cell assay to detect PT neutralizing antibody will be performed only in the same subset of 75 subjects (25 subjects in each vaccine group) who had been selected for PT neutralizing antibody assessment in the previous TDA202 study.

The knowledge from this long-term 3-year antibody persistence study will provide supportive data to identify the best alternative acellular pertussis vaccines to conventional chemically-detoxified vaccines for controlling the resurgence of pertussis disease.

Data management and statistical analysis will be performed by Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Bangkok, Thailand.

Eligibility criteria: Inclusion Criteria:

1. Having participated in TDA202 study, received a single dose of one of the 3 study vaccines, and completed 1 year follow-up visit.
2. Written informed consent is obtained for subjects aged ≥18 years, or written assent and written informed consent are obtained from subjects aged \<18 years and from their parent/legal guardian, respectively, prior to study entry.
3. Capable to comply with study procedures and willing to provide with a blood sample.

Exclusion Criteria:

No exclusion criteria for this study. Subjects will be eligible for participation if all inclusion criteria are met.

Primary outcomes:
measure: Comparison of anti-PT GMTs (IU/mL) between baseline and 3 years after vaccination
timeFrame: 3 years after vaccination ± 1 month
measure: Comparison of anti-FHA GMTs (IU/mL) between baseline and 3 years after vaccination
timeFrame: 3 years after vaccination ± 1 month
measure: Comparison of anti-Tetanus GMTs (IU/mL) between Day 336 and 3 years after vaccination
timeFrame: 3 years after vaccination ± 1 month
measure: Comparison of anti-Diphtheria GMTs (IU/mL) between Day 336 and 3 years after vaccination
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with anti-PT antibody titers at 3 years after vaccination compared to baseline in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with anti-FHA antibody titers at 3 years after vaccination compared to baseline in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with ≥ 2-fold increase in anti-PT antibody titers at 3 years after vaccination compared to baseline, Day 336 and 2 years after vaccination in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with ≥ 2-fold increase in anti-FHA antibody titers at 3 years after vaccination compared to baseline, Day 336 and 2 years after vaccination in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with ≥ 4-fold increase in anti-PT antibody titers at 3 years after vaccination compared to baseline, Day 336 and 2 years after vaccination in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with ≥ 4-fold increase in anti-FHA antibody titers at 3 years after vaccination compared to baseline, Day 336 and 2 years after vaccination in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with > 0.1 IU/mL of anti-Tetanus at baseline and 3 years after vaccination compared to baseline in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of subjects with > 0.1 IU/mL of anti-Diphtheria at baseline and 3 years after vaccination compared to baseline in all evaluable subjects by vaccine groups
timeFrame: 3 years after vaccination ± 1 month
measure: Comparison of PT neutralizing GMTs (IU/mL) between baseline and 3 year after vaccination
timeFrame: 3 years after vaccination ± 1 month
measure: Seroconversion rates of PT neutralizing antibody increase ≥ 4-fold at 3 years after vaccination compared to baseline, Day 336 and 2 years after vaccination
timeFrame: 3 years after vaccination ± 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Vaccine Trial Centre, Faculty of Tropical Medicine, Mhahidol University, 420/6 Ratchawithi Road, Ratchathewi,
Study officials:
affiliation: VTC, Faculty of Tropical Medicine, Mahidol University
name: Punnee Pitisuttithum, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pitisuttithum P, Chokephaibulkit K, Sirivichayakul C, Sricharoenchai S, Dhitavat J, Pitisuthitham A, Phongsamart W, Boonnak K, Lapphra K, Sabmee Y, Wittawatmongkol O, Chauhan M, Wijagkanalan W, Hommalai G, Fortuna L, Chinwangso P, Poredi IK, van den Biggelaar AHJ, Pham HT, Viviani S. Antibody persistence after vaccination of adolescents with monovalent and combined acellular pertussis vaccines containing genetically inactivated pertussis toxin: a phase 2/3 randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2018 Nov;18(11):1260-1268. doi: 10.1016/S1473-3099(18)30375-X. Epub 2018 Sep 25.