A Phase 4, Randomised Vaccination Study in Healthy Adults to Investigate the Effects of Acellular Pertussis Vaccine on Colonisation With Bordetella Pertussis Using Controlled Human Infection

NCT06903221 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 2023-508416-35-00
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate the effect of booster vaccination with acellular pertussis vaccine on colonization with Bordetella pertussis using a controlled human infection model in healthy volunteers. The main questions it aims to answer are:

• Whether booster vaccination with Tdap-IPV reduces Bp colonisation after intranasal challenge with the standard Bp inoculum dose compared to the Td-IPV control group
• Compare Bp colonisatation in participants vaccinated with Tdap-IPV after intranasal challenge with the standard and a 'high' Bp inoculum dose Research will compare Tdap-IPV vaccination - standard inoculum dose with Td-IPV vaccination - standard inoculum dose, and Tdap-IPV vaccination - standard inoculum dose with Tdap-IPV vaccination - high inoculum dose to see how Tdap-IPV vaccination and the high inoculum dose have an effect on colonisation rate. Participants will be vaccinated with Tdap-IPV or Td-IPV and 2-4 months later challenged with the standard or 'high' inoculum. After challenge there is a follow up visit for 28 days in which they fill in a daily symptom diary and have 6 visits to the hospital.

Conditions

Pertussis Infection; Pertussis Vaccines

Keywords

Controlled human infection model; Pertussis; Pertussis vaccine; Acellular pertussis vaccine; Tdap-IPV

Outcome Measures

Primary Outcomes (1)

• Bordetella pertussis (Bp) colonisation rate

  Bp colonisation rate in Tdap-IPV and Td-IPV vaccination groups, with Bp colonisation defined as any positive Bp culture from nasal wash samples at any time point between Day 3 and Day 28 after challenge

  Day 3-28 post challenge

Secondary Outcomes (5)

• Safety: solicited adverse events (AEs)

  Day 0-28 post challenge

• Safety: azithromycin treatment

  Day 0-28 post challenge

• Safety: unsolicited AEs

  Day 0-28 post challenge

• Colony forming unit (CFU) counts

  Day 3-28 post challenge

• Geometric mean concentration of Bp-specific antibodies

  5 months

Study Arms (3)

Tdap-IPV - standard inoculum dose

EXPERIMENTAL

Participants get vaccinated with Tdap-IPV and will be challenged with 10E5 CFU Bordetella pertussis

Drug: Tdap-IPV

Td-IPV - standard inoculum dose

PLACEBO COMPARATOR

Participants get vaccinated with Td-IPV and will be challenged with 10E5 CFU Bordetella pertussis

Drug: Td-IPV

Tdap-IPV - high inoculum dose

EXPERIMENTAL

Participants get vaccinated with Tdap-IPV and will be challenged with 10E6 CFU Bordetella pertussis

Drug: Tdap-IPV

Interventions

Tdap-IPV DRUG

intramuscular injection

Also known as: acellular pertussis vaccine

Tdap-IPV - high inoculum dose; Tdap-IPV - standard inoculum dose

Td-IPV DRUG

intramuscular injection

Td-IPV - standard inoculum dose

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant (male/female) is born before 1-9-2004 and \< 50 years old on the day of screening
• Participant has received all primary pertussis vaccines during childhood
• Participant is in good health as confirmed by review of medical history and physical examination
• Participant has adequate understanding of the procedures of the study and agrees to abide strictly thereby
• Participant is able to answer all questions of the pre-consent questionnaire correctly
• Participant is fully conversant in the Dutch language
• Participant is capable and willing to give personal signed informed consent.
• Participant is able to communicate by both mobile telephone and text messaging
• Participant is willing and available to attend all study visits
• Participant agrees to inform his/her general practitioner (GP) about participation in the study
• Participant agrees to provide access to information regarding their vaccination background
• Participant agrees to provide a treating physician access to all study-related information and data
• Participant is able to arrive within 1h at the Radboudumc from his/her home address. The participant must have a home address and live in the Netherlands
• Participant is able to arrive within 3h at the Radboudumc at any time between Bp inoculation until the day 28 post challenge visit
• Participant is willing to take an antibiotic regimen after inoculation with Bp according to the study protocol

You may not qualify if:

• Incapacitated subjects without decision-making capacity.
• A confirmed diagnosis of pertussis in the last two years and/or serum IgG anti-FHA \>56 IU/mL
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Individuals who are at risk of complications of a prolonged cough, such as individuals with stress urine incontinence, pelvic floor dysfunction or an inguinal hernia
• Chronic use of i) immunosuppressive drugs (e.g. systemic steroids, steroid nasal spray or isotretinoin), ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
• Drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset
• Diabetes mellitus
• Smoking: Any smoking event in the last month, including (e-)cigarette, joint, cigar and pipe
• Infection with Bp or any other Bordetella species at the baseline for challenge visit
• Individuals who have a history of receiving pertussis vaccination in the last 5 years
• Acute illness within 3 days prior to Bp inoculation (including mild upper respiratory tract infection, common cold, running nose)
• Any antibiotic treatment within 4 weeks before inoculation

Sponsors & Collaborators

• Dimitri Diavatopoulos: lead

Study Sites (1)

RadboudUMC

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Whooping Cough

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior researcher

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start: October 16, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Locations

NL (1)