Study to Evaluate the Immune Response After Booster Vaccination With Tdap-IPV Vaccine (Against Tetanus, Diphtheria, Pertussis and Poliomyelitis) in Children Who Received Different Pertussis Primary Vaccine Regimens in Republic of South Africa

Diphtheria Immunisation Clinical Trial

Official title:

Immune Response to Pertussis After Vaccination With a Tdap-IPV Booster Vaccine in Children in the Republic of South Africa: Effect of Homologous and Heterologous Pertussis Vaccination Priming Background

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04300192
• Other study ID #: TD500056
• Secondary ID: U1111-1223-5186
• Status: Completed
• Phase: Phase 4
• Start date: January 27, 2021
• Est. completion date: January 11, 2023

Study information

• Verified date: March 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objectives :

• To describe the long-term humoral immune responses to pertussis, diphtheria, and tetanus after homologous and heterologous pertussis vaccine priming regimens

• To determine the effects of the priming regimen on humoral responses to booster vaccination with Tdap-IPV vaccine

• To describe the long-term cell-mediated immune responses to pertussis after homologous and heterologous pertussis vaccine priming regimens

• To determine the effects of the priming regimen on cell-mediated immune response to booster vaccination with Tdap-IPV vaccine

Secondary Objective:

To describe the safety profile of Tdap-IPV vaccine in each group

Description:

Study duration per participant will be approximately 30 days including: 1 day of screening and vaccination, a phone call and a safety follow-up/end of study visit, at Day 8 and Day 30 after vaccine administration, respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: January 11, 2023
• Est. primary completion date: January 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 14 Years

Eligibility

Inclusion Criteria:

• Born in 2007 to 2011 in the RSA

• Received primary pertussis vaccination and the toddler booster in the RSA

• Assent form has been signed and dated by the participant, and informed consent form (ICF) has been signed and dated by the parent(s) or another legal guardian and by an independent witness, if required by local regulations

• Participants and parent/legal guardian are able to attend all scheduled visits and to comply with all trial procedures

• Valid clinical record of primary vaccination with DTaP/DTwP vaccines immunization history from 2007 through 2011, either by hand-held (Road-to-Health Card) or immunization clinical records

• For Groups 6 and 7: children infected with perinatally acquired HIV infection currently under care who received either an all wP or all aP priming regimen

• For Groups 6 and 7: be on highly active antiretroviral therapy (HAART) therapy and have known CD4 cell counts > 200 cells/µL

Exclusion Criteria:

• Participation in the 4 weeks preceding the vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure

• Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination except for influenza

• Receipt of additional pertussis vaccination doses inconsistent with pertussis vaccination schedule in the RSA

• Previous confirmed diagnosis of pertussis disease

• Receipt of immune globulins, blood or blood-derived products in the past 3 months

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances

• For Groups 1 to 5: known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

• Known thrombocytopenia, as reported by the parent/ legal guardian or suspected thrombocytopenia contraindicating intramuscular vaccination in the Investigator's opinion

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination

• Participants with progressive neurological disorder, uncontrolled epilepsy, or progressive encephalopathy except if a treatment regimen has been established and the condition has stabilized

• Encephalopathy within 7 days of a previous dose of pertussis-containing vaccine

• Had contraindication to receipt of Adacel Quadra vaccine at the time of vaccination as defined in the Adacel Quadra vaccine Republic of South Africa (RSA) label

• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature = 38.0°C [= 100.4°F]). A prospective participants should not be included in the study until the condition has resolved or the febrile event has subsided (temporary contraindication)

• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw Note: Potential participants receiving standard HIV treatments such as antiretrovirals and/or antibiotic prophylaxis can be enrolled in the study. Their routine medications should be documented in the CRB.

• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study

Related Conditions & MeSH terms

• Diphtheria
• Diphtheria Immunisation
• Pertussis Immunisation
• Poliomyelitis
• Tetanus
• Tetanus Immunisation
• Whooping Cough

Intervention

Biological:
• Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine
Pharmaceutical form:Suspension for injection Route of administration: Intramuscular

Locations

Country	Name	City	State
South Africa	Investigational Site Number :7100001	Cape Town
South Africa	Investigational Site Number :7100003	Johannesburg
South Africa	Investigational Site Number :7100002	Middelburg

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Concentrations (GMCs) of anti-pertussis total immunoglobulin G (IgG)	Total IgG anti-pertussis antibody concentrations against the following pertussis antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM)	Day 0 (pre-vaccination) and Day 30 (post-vaccination)
Primary	GMCs of anti-diphtheria IgG	Total IgG anti-diphtheria antibody concentrations	Day 0 (pre-vaccination) and Day 30 (post-vaccination)
Primary	GMCs of anti-tetanus toxoid IgG	Total IgG anti-tetanus antibody concentrations	Day 0 (pre-vaccination) and Day 30 (post-vaccination
Primary	GMCs of anti-pertussis total immunoglubulin A (IgA) and of anti-heat-killed B pertussis (HK Bp) IgA in cell-mediated immunity (CMI) subset only	Total IgA anti-pertussis antibody concentrations against the following pertussis antigens: PT, FHA, PRN, FIM types 2 and 3, and heat-killed B. pertussis (HK Bp)	Day 0 (pre-vaccination) and Day 30 (post-vaccination)
Primary	Geometric Mean (GM) of anti-pertussis IgG subclasses and of anti-HK Bp IgG subclasses.	Anti-pertussis IgG subclasses (ie, IgG1, IgG2, IgG3, and IgG4) distribution against PT, FHA, PRN, FIM types 2 and 3, and HK Bp	Day 0 (pre-vaccination) and Day 30 (post-vaccination)
Primary	GM of pertussis antigen-specific T cells	Absolute numbers (spot forming cells [SFC]/10e6 PBMCs) of pertussis antigen-specific (antigen pool and HK Bp) interferon (IFN)-?, interleukin (IL)-17, IL-4 secreting cells	Day 0 (pre-vaccination) and Day 30 (post-vaccination)
Secondary	Number of participants reporting immediate adverse events (AEs)	Medically relevant unsolicited systemic AEs, including those related to the product administered	Within 30 minutes post-vaccination
Secondary	Number of participants reporting solicited injection site reactions and systemic reactions	Adverse reactions prelisted in the (electronic) case report book (CRB) Injection site reactions: pain, erythema, swelling Systemic reactions: fever, headache, malaise, myalgia	Within 7 days post-vaccination
Secondary	Number of participants reporting unsolicited AEs	AEs other than solicited reactions	Within 30 days post-vaccination
Secondary	Number of participants reporting serious adverse events (SAEs)	SAEs, including adverse event of special interest (AESIs)	Up to 37 days post-vaccination