Immunogenicity of a Combined Diphtheria-Tetanus-recombinant Acellular Pertussis (DTaP) Vaccine in Healthy Toddlers

A Phase II/III Randomized, Observer-blind, Active-controlled Study to Compare Non-inferior Immunogenicity of a DTaPgen Vaccine to a Licensed DTaP-IPV, When Administered to Healthy Toddlers Aged of 15-36 Months Old.

Recombinant acellular pertussis vaccines containing genetically detoxified Pertussis Toxin (PTgen) have been used for booster immunisation in children, adolescents and adults including pregnant women in Thailand. Three vaccines have been licensed in Thailand, a monovalent (aPgen) and two vaccines combined with tetanus and reduced diphtheria dose vaccines (TdaPgen and Tdapgen). To address the need for improved vaccines in younger children, a new recombinant pediatric DTaP vaccine (DTaPgen) containing 5 µg genetically detoxified Pertussis Toxin (PTgen) and 10 µg Filamentous Hemagglutinin (FHA) was developed and found safe and immunogenic in a phase II trial in children aged 3 years onwards.

The purpose of this study is to assess the immunogenicity and safety of this new pediatric formulation DTaPgen given as the first booster dose in healthy toddlers aged 15 to 36 months compared to a commercially available vaccine in Thailand.

This is a phase II/III randomized, observer-blind, active-controlled study conducted in Thailand, children aged 15-36-month-old with a history of DTwP (n=240) or DTaP (n=50) priming were randomized 2:1 to receive a dose of recombinant DTaPgen or licensed DTaP-IPV. The aim of this study is to evaluate the safety and non-inferior immunogenicity of DTaPgen versus DTaP-IPV vaccine given as the first booster dose in toddlers.

Safety up to 1-year and vaccine antibody persistence will also be assessed for all children.

Inclusion Criteria: Participants will be eligible for inclusion if ALL of the following criteria are met at the time of screening:

1. 15 to 36 months of age at the time of vaccination.
2. Having completed the 3-dose DTwP or 3-dose DTaP vaccination (no interchange of DTwP and DTaP during primary immunization).
3. The parents or legal guardians of the participant are able to read and write.
4. The parents or legal guardians can provide written informed consent.
5. Healthy, as established by pertinent medical history and physical examination.

Exclusion Criteria: A participant with ANY of the following criteria at study entry will not be eligible for participation

1. History of any significant medical illness such as, but not limited to, immune deficiency, renal, hepatic, cardiovascular, or endocrine disorder as determined by the investigator based on medical history and physical examination.
2. History of allergy or hypersensitivity to any vaccine (including its component).
3. History of any serious adverse event or neurological adverse event after vaccination.
4. Having received only 1 or 2 doses of DTwP or DTaP (incomplete primary immunization) after birth until the study enrollment.
5. Having received the 4th dose DTwP or DTaP vaccination.
6. Having experienced a physician diagnosed diphtheria or tetanus or pertussis illness within 1 year prior to recruitment.
7. Receipt of any vaccine within 28 days prior to enrollment (3 months for live-attenuated vaccines).
8. Planning to receive tetanus, diphtheria, pertussis or planning to participate in another clinical trial during the study period (approximately 1 year).
9. Receipt of blood or blood component or immunoglobulin within 3 months prior to recruitment.
10. History of receiving any immunosuppressive drug or systemic corticosteroid (more than 0.5 mg/kg of prednisolone or equivalent for more than 14 days) within 3 months prior to recruitment.
11. Any bleeding disorder.
12. Any abnormality of splenic or thymic function.
13. Any progressive or severe neurological disorder such as seizure disorder or Guillain- Barre syndrome;
14. History of any illness including cognitive impairment and psychiatric disease that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the participants due to participation in the study.
15. Fever as defined by body temperature more than 38 degree celsius at the time of enrollment (temporary exclusion criterion).