10-year Follow-up After a Single Dose Acellular Pertussis Vaccination

Antibody Persistence and Safety and Immunogenicity of a Second Booster Dose 10 Years After a First Booster Vaccination With a Single Dose Vaccination of aP Vaccine in Adults: A Phase IV, Open-label, Non-randomized, Follow-up Study

This is a phase IV, open-label, non-randomized study to demonstrate superior immunogenicity and safety of a second booster dose of Pertagen® as compared to Adacel® at 10 years after the first booster vaccination and to evaluate the long-term persistence of specific antibodies induced by BioNet's recombinant aP (Pertagen®) and TdaP (Boostagen®) vaccines and a chemically-detoxified Tdap vaccine (Adacel®) at 10 years after the first booster in participants who were vaccinated in the phase II/III trial (Protocol No. TDA202).

Study Overview

• Status: Recruiting
• Conditions: Pertussis
• Intervention / Treatment: Biological: Pertagen® vaccine; Biological: Adacel® vaccine

Detailed Description

This is a phase IV, open-label, non-randomized study to demonstrate superior immunogenicity and safety of a second booster dose of Pertagen® as compared to Adacel® at 10 years after the first booster vaccination and to evaluate the long-term persistence of specific antibodies induced by BioNet's recombinant aP (Pertagen®) and TdaP (Boostagen®) vaccines and a chemically-detoxified Tdap vaccine (Adacel®) at 10 years after the first booster in participants who were vaccinated in the phase II/III trial (Protocol No. TDA202) conducted from July 2015 to November 2016. Only those who were enrolled in the initial TDA202 study and had completed TDA202 1-year follow-up will be recruited for this 10-year follow-up study.

Participants from all 3 vaccine groups (i.e., participants who had received a single dose of one of the 3 study vaccines (Boostagen®, Pertagen®, or Adacel®) and completed 1-year follow-up visit at Day 336±28 days during the TDA202 study will be called in for informed consent process at Visit 0 (Screening) at approximately 10 years (range, 9.5-10 years) following vaccination.

At Visit 0, Screening visit, participants who have signed the written Informed Consent Forms will be screened for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination) and those who fulfill the pre-defined inclusion criteria without meeting any exclusion criteria will be enrolled into the study. The screening visit and Visit 1 (Day 0) can be completed on the same day. Once enrolled, a blood sample (approx. 5 mL) will be taken from all participants at Visit 1 (before second booster vaccination) and at Visit 2 (28 days after second booster vaccination) as shown in the diagram below (Figure 1).

At Visit 1, Day 0 (enrollment and second booster vaccination), a blood sample (approx. 5 mL) will be taken from all enrolled participants. After blood collection, the participants who received Pertagen® and Boostagen® in the initial TDA202 study will be administered a single intramuscular injection of a second booster dose of Pertagen®. The participants who have received Adacel® in the initial TDA202 study will be given a single intramuscular injection of a second booster dose of Adacel® (Table 1). Composition of booster vaccines are presented in Table 2. The vaccine preparation and administration will be performed by appropriately trained study team and study nurses, respectively, who are delegated by the Principal Investigator.

If a participant does not complete screening visit and Visit 1 (Day 0) on the same day, the screening process for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination), urine pregnancy test for female participants with childbearing potential and inclusion and exclusion criteria will be assessed again at Visit 1.

Brief description of the study design for TDA202 10-year follow-up study:

This is a phase IV, open-label, non-randomized study to demonstrate superior immunogenicity and safety of a second booster dose of Pertagen® as compared to Adacel® at 10 years after the first booster vaccination and to evaluate the long-term persistence of specific antibodies induced by BioNet's recombinant aP (Pertagen®) and TdaP (Boostagen®) vaccines and a chemically-detoxified Tdap vaccine (Adacel®) at 10 years after the first booster in participants who were vaccinated in the phase II/III trial (Protocol No. TDA202) conducted from July 2015 to November 2016. Only those who were enrolled in the initial TDA202 study and had completed TDA202 1-year follow-up will be recruited for this 10-year follow-up study.

Participants from all 3 vaccine groups (i.e., participants who had received a single dose of one of the 3 study vaccines (Boostagen®, Pertagen®, or Adacel®) and completed 1-year follow-up visit at Day 336±28 days during the TDA202 study will be called in for informed consent process at Visit 0 (Screening) at approximately 10 years (range, 9.5-10 years) following vaccination.

At Visit 0, Screening visit, participants who have signed the written Informed Consent Forms will be screened for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination) and those who fulfill the pre-defined inclusion criteria without meeting any exclusion criteria will be enrolled into the study. The screening visit and Visit 1 (Day 0) can be completed on the same day. Once enrolled, a blood sample (approx. 5 mL) will be taken from all participants at Visit 1 (before second booster vaccination) and at Visit 2 (28 days after second booster vaccination) as shown in the diagram below (Figure 1).

At Visit 1, Day 0 (enrollment and second booster vaccination), a blood sample (approx. 5 mL) will be taken from all enrolled participants. After blood collection, the participants who received Pertagen® and Boostagen® in the initial TDA202 study will be administered a single intramuscular injection of a second booster dose of Pertagen®. The participants who have received Adacel® in the initial TDA202 study will be given a single intramuscular injection of a second booster dose of Adacel® (Table 1). Composition of booster vaccines are presented in Table 2. The vaccine preparation and administration will be performed by appropriately trained study team and study nurses, respectively, who are delegated by the Principal Investigator.

If a participant does not complete screening visit and Visit 1 (Day 0) on the same day, the screening process for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination), urine pregnancy test for female participants with childbearing potential and inclusion and exclusion criteria will be assessed again at Visit 1.

Table 1: Vaccine groups and booster dose vaccination Vaccine group in Initial TDA202 study Second booster vaccination at Day 0 Total number of participants (N) per vaccine group Pertagen® and Boostagen® Pertagen® 84 Adacel® Adacel® 42 After the second booster vaccination, participants will be observed at the study site for at least 30 minutes to monitor for any immediate post-immunization reactions. Safety and reactogenicity in the participants will be assessed until end of study. The diary cards will be distributed to the participants to record post-immunization solicited local and systemic adverse events (AEs) until Day 7 and unsolicited AEs, serious adverse events (SAEs), and concomitant medications until Day 28 following vaccination. The study staff will contact the participants by phone on Day 7 (+4 days) to enquire on health status and to remind them to record any solicited local and systemic AEs, unsolicited AE, SAE and concomitant medications in the diary card.

At Visit 2, Day 28 (+7 days), participants will return to the study site for blood sample collection (approx. 5 mL), reconciliation of information in the diary card, and any reported AEs, SAEs and concomitant medications.

Safety and reactogenicity will be assessed until end of study. Solicited local and systemic AEs will be collected until Day 7 after the second booster vaccination. Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) will be collected until Visit 2 (Day 28) after the second booster vaccination. Visit 2 is considered the end of study.

Blood samples collected from all participants at Day 0 (Visit 1) and Day 28 (Visit 2) will be processed for serum preparation. Serum samples will be stored at the laboratory at the study site and will be further shipped to BioNet-Asia Human Serology Laboratory where immunogenicity testing will be performed. At Day 0 (Visit 1) and Day 28 (Visit 2), ELISA testing to detect antibodies against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and PT neutralizing assay in Chinese Hamster Ovary (CHO) cells will be performed for all enrolled participants. At Day 0 (Visit 1), ELISA testing to detect antibodies against tetanus toxoid (TT) and diphtheria toxoid (DT) will be performed for participants who received Boostagen® and Adacel® in TDA202 initial study.

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

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Punnee Pitisuttithum; Phone Number: 0818294906; Email: punnee.pit@mahidol.ac.th
• Study Contact Backup: Name: Jittima Dhitavat; Phone Number: 0875921777; Email: ่jittima_pu@yahoo.com

Study Locations

• Thailand
  • Bangkok Metropolis
    • Bangkok Noi, Bangkok Metropolis, Thailand, 10700
      • Recruiting
      • Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University
      • Contact: Prof. Kulkanya Chokephaibulkit, M.D.; Email: kulkanya.cho@mahidol.ac.th
    • Ratchathewi, Bangkok Metropolis, Thailand, 10400
      • Recruiting
      • Vaccine Trial Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

A participant will be eligible for inclusion if ALL of the following apply at the time of screening:

1. Having participated in the initial 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 prior to study entry;
3. Healthy, as established by pertinent medical history and physical examination;
4. Capable of complying with study procedures and willing to provide with a blood sample;
5. For women with childbearing potential (i.e., urine pregnancy test will not be performed in females who have undergone sterilisation, hysterectomy or who are post-menopausal), must have a negative urine pregnancy test at enrollment and willing to take reliable birth control measures for one month following vaccination.

Exclusion Criteria:

A participant with following criteria at screening will not be eligible for participation:

1. Having received any pertussis vaccine since completion of 1-year follow-up visit in the initial TDA202 study;
2. Having experienced physician-diagnosed pertussis since completion of 1-year follow-up visit in the initial TDA202 study prior to enrollment;
3. Pregnant or breast-feeding women or female participants who intend to become pregnant during study period;
4. History of any significant medical illness such as, but not limited to, immune deficiency, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or hepatic, renal, or endocrine disorder, splenic or thymic functional abnormality as determined by the investigator based on medical history and physical examination that may interfere with the participant's safety and evaluation of investigational vaccines in this study;
5. History of allergy or hypersensitivity to any vaccine (including its component);
6. History of any serious adverse event or neurological adverse event after vaccination;
7. History of receiving blood or blood component or immunoglobulin within 3 months prior to enrollment;
8. History of receiving immunosuppressive drugs or systemic corticosteroid (>0.5 mg/kg of prednisolone or equivalent for more than 14 days) within 3 months prior to enrollment;
9. Having received any other vaccines within 28 days prior to enrollment (3 months for live- attenuated vaccines);
10. Plan to receive any other vaccine or plan to participate in another clinical trial with intervention during the study period;
11. A known bleeding diathesis or any condition that may be associated with a prolonged bleeding time resulting in a problem with intramuscular injection;
12. Any progressive or severe neurological disorder such as seizure disorder or Guillain-Barré syndrome;
13. History of any illness or clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the volunteers due to participation in the study
14. Fever as defined by body temperature ≥ 38°C at the time of enrollment (This is a temporary exclusion criterion).

Remark: If fever occurs at screening visit, the participant may be rescreened and enrolled at a later date at the discretion of the investigator, or withdrawn at the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pertagen® vaccine; Pertagen® vaccine, manufactured by BioNet-Asia Co., Ltd., Bangkok, Thailand. The vaccine is presented in pre-filled syringe, each containing one human dose (0.5 mL) of aP vaccine.	Biological: Pertagen® vaccine; Pertagen® vaccine, manufactured by BioNet-Asia Co., Ltd., Bangkok, Thailand. The vaccine is presented in pre-filled syringe, each containing one human dose (0.5 mL) of aP vaccine.
Experimental: Adacel® vaccine; Adacel® vaccine, manufactured by Sanofi Pasteur, Ltd, Toronto, Ontario, Canada. The vaccine is presented in a single-dose vial, each containing one human dose (0.5 mL) of Tdap vaccine.	Biological: Adacel® vaccine; Adacel® vaccine, manufactured by Sanofi Pasteur, Ltd, Toronto, Ontario, Canada. The vaccine is presented in a single-dose vial, each containing one human dose (0.5 mL) of Tdap vaccine.
Experimental: Boostagen® vaccine; BIoNet Recombinant TdaP, each 0.5 mL dose of Boostagen (TdaP BioNet) contained 5 μg PTgen, 5 μg FHA, and 0.3 mg as aluminium cation.	Biological: Pertagen® vaccine; Pertagen® vaccine, manufactured by BioNet-Asia Co., Ltd., Bangkok, Thailand. The vaccine is presented in pre-filled syringe, each containing one human dose (0.5 mL) of aP vaccine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate superiority at 28 days post-booster vaccination with one dose of Pertagen® as compared to Adacel®.	Geometric mean concentration (GMC) of anti-PT and anti-FHA antibodies measured at baseline (before second booster vaccination) and 28 days following vaccination.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity endpoints at 28 days post-booster vaccination with one dose of Pertagen® as compared to Adacel®.	• GMC of PT neutralizing antibody (PTNA) measured at baseline (before second booster vaccination) and 28 days following vaccination.	Day 28
Immunogenicity endpoints at 28 days post-booster vaccination with one dose of Pertagen® as compared to Adacel®.	• Seroconversion rates as defined by proportion of participants with antibody concentrations ≥ 4-fold increase with respect to baseline (before first and second booster vaccination) of anti-PT and anti-FHA, and PT- neutralizing antibodies at 28 days after booster dose vaccination.	Day 28
Immunogenicity endpoints at 28 days post-booster vaccination with one dose of Pertagen® as compared to Adacel®.	• Seropositive rates as defined by proportion of participants with antibody concentrations > 5 IU/mL for anti-PT and anti-FHA, and PT-neutralizing antibodies at baseline (before first and second booster vaccination) and 28 days after booster dose vaccination.	Day 28
Immunogenicity endpoints at 28 days post-booster vaccination with one dose of Pertagen® as compared to Adacel®.	• Booster response rates as defined by proportion of participants with antibody concentrations >20 IU/mL for anti-PT and anti-FHA, and PT-neutralizing antibodies at baseline (before first and second booster vaccination) and 28 days after booster dose vaccination.	Day 28
Immunogenicity endpoints at 28 days post-booster vaccination with one dose of Pertagen® as compared to Adacel®.	• The proportion of participants with cut-off levels of anti-PT, anti-FHA and PT-neutralizing antibodies (i.e, ≥ 5, > 5, ≥ 10, ≥ 20, ≥ 30, ≥ 40, ≥ 50, ≥ 80, ≥ 100, ≥ 120 IU/mL) in Pertagen® and Adacel® at baseline (before first and second booster vaccination) and 28 days after booster dose vaccination.	Day 28
Immunogenicity endpoints for antibody response before second booster vaccination at 10 years after a single dose vaccination of Boostagen® and Pertagen® as compared to Adacel® from initial TDA202 study	• GMCs of anti-PT, anti-FHA and PT-neutralizing antibodies in all vaccine groups and GMCs of anti-TT and anti-DT antibodies in Boostagen® and Adacel® at 10 years after vaccination	10 years safter vaccination
Immunogenicity endpoints for antibody response before second booster vaccination at 10 years after a single dose vaccination of Boostagen® and Pertagen® as compared to Adacel® from initial TDA202 study	• Seropositive rates as defined by proportion of participants with antibody concentrations >5 IU/mL for anti-PT and anti-FHA, and PT-neutralizing antibodies at 10 years after vaccination	10 years safter vaccination
Immunogenicity endpoints for antibody response before second booster vaccination at 10 years after a single dose vaccination of Boostagen® and Pertagen® as compared to Adacel® from initial TDA202 study	• Booster response rates as defined by proportion of participants with antibody concentrations >20 IU/mL for anti-PT and anti-FHA, and PT neutralizing antibodies at 10 years after vaccination	10 years safter vaccination
Immunogenicity endpoints for antibody response before second booster vaccination at 10 years after a single dose vaccination of Boostagen® and Pertagen® as compared to Adacel® from initial TDA202 study	• Seroconversion rates as defined by proportion of participants with antibody concentrations ≥ 2-fold increase with respect to baseline of anti-PT and anti-FHA, and PT-neutralizing antibodies at 10 years after vaccination	10 years safter vaccination
Immunogenicity endpoints for antibody response before second booster vaccination at 10 years after a single dose vaccination of Boostagen® and Pertagen® as compared to Adacel® from initial TDA202 study	• Seroconversion rates as defined by proportion of participants with antibody concentrations ≥ 4-fold increase with respect to baseline, of anti-PT and anti-FHA, and PT-neutralizing antibodies at 10 years after vaccination	10 years safter vaccination
Immunogenicity endpoints for antibody response before second booster vaccination at 10 years after a single dose vaccination of Boostagen® and Pertagen® as compared to Adacel® from initial TDA202 study	• Seroprotection rate as defined by proportion of participants with antibody concentrations > 0.1 IU/mL of anti-TT and anti-DT antibodies in Boostagen® and Adacel® vaccine groups at 10 years after vaccination. The proportion of participants with cut-off levels of anti-PT, anti-FHA and PT-neutralizing antibodies (i.e, ≥ 5, > 5, ≥ 10, ≥ 20, ≥ 30, ≥ 40, ≥ 50, ≥ 80, ≥ 100, ≥ 120 IU/mL) in Pertagen®, Boostagen® and Adacel® at 10 years after vaccination	10 years safter vaccination
Safety endpoints at 28 days post-booster vaccination with one dose of Pertagen® and Adacel®	• Percentage of participants with solicited local and systemic AEs reported within 7 days after booster vaccination	From Day 0 to Day 7
Safety endpoints at 28 days post-booster vaccination with one dose of Pertagen® and Adacel®	• Percentage of participants with unsolicited AEs reported from the day of booster vaccination through 28 days following booster vaccination	From Day 0 to Day 28
Safety endpoints at 28 days post-booster vaccination with one dose of Pertagen® and Adacel®	• Percentage of participants with SAEs reported from the day of booster vaccination through 28 days following booster vaccination	From Day 0 to Day 28

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: BioNet-Asia Co., Ltd.
• Investigators: Principal Investigator: Punnee Pitisuttithum, Vaccine Trial Centre

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: January 27, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): January 31, 2025

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: TDA202; acellular pertussis vaccine; Pertagen; Boostagen; aP vaccine; a second booster dose of Pertagen® as compared to Adacel®; antibody persistence at 10 years after vaccination
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Bordetella Infections; Whooping Cough; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: TDA 202 10-year follow-up

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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