Maternal Pertussis Wholecell Responses

NCT04589312 | Completed Phase 2 DMC

• 1 other identifier: 17.0019
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 1

Brief Summary

Pertussis is resurging worldwide. In Africa alone it is estimated that there are 2.1 million cases and 542,000 deaths from pertussis in infants under 1 year with the highest rates of morbidity and mortality in infants \<3 months old, before possible prevention via the infant immunization programme1. To protect these most vulnerable infants, the World Health Organisation (WHO) recommends Tdap vaccination as safe in pregnancy and recommends the use of wP vaccines within the EPI. Maternal antibody following aP vaccination can interfere with infant anti-pertussis antibody responses post infant EPI vaccination, which is of concern in high burden settings such as Uganda. There are therefore multiple factors in this population which may influence the effect of pertussis immunization in pregnancy, and which have not been studied, most notably HIV infection and interference with wP vaccines in infants. The immunogenicity of Tdap in HIV-infected pregnant women has not yet been examined. In addition, to date, the effect of maternal vaccination, placental transfer and infant antibody responses in HEU infants have not been studied at all. There are no studies examining the immune response to wP vaccine administered to infants (EPI recommendation) whose mothers received aP in pregnancy.

Conditions

Pertussis

Keywords

Whooping Cough; Pertussis; Vaccination; Pregnancy; Infant; Newborn; HIV

Outcome Measures

Primary Outcomes (10)

• Anti-pertussis toxin (PT) and anti-FHA IgG concentrations in cord blood of Tdap-vaccinated HIV-infected vs HIV-uninfected pregnant women.

  At delivery

• Anti-pertussis toxin (PT) and anti-FHA IgG concentrations in cord blood of Tdap -vaccinated vs Tdap -unvaccinated pregnant women and whether this differs by maternal HIV status.

  At delivery

• Anti-PT and anti-FHA IgG concentrations in infants born to Tdap vaccinated vs Tdap -unvaccinated pregnant women 4 weeks after the completion of a series of primary vaccination with 3 doses of wP vaccine, and whether this differs by maternal HIV status.

  18 weeks of pregnancy

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Pregnant Women

  Percentage of maternal Subjects With Solicited Local and Solicited Systemic AEs and percentage with any Unsolocited AEs; Percentage of Maternal Subjects With Serious Adverse Events (SAEs), Unsolicited Medically Attended AEs (MAEs) and Unsolicited AEs Leading to Study Withdrawal

  First vaccination visits

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Pregnant Women

  Percentage of maternal Subjects With Solicited Local and Solicited Systemic AEs and percentage with any Unsolocited AEs; Percentage of Maternal Subjects With Serious Adverse Events (SAEs), Unsolicited Medically Attended AEs (MAEs) and Unsolicited AEs Leading to Study Withdrawal

  At 12 months of age of infants

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Infants

  Percentage of Infants With SAEs, Unsolicited AEs and AEs Leading to Study Withdrawal by a clinical examination

  At birth

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Infants

  Percentage of Infants With SAEs, Unsolicited AEs and AEs Leading to Study Withdrawal by a clinical examination

  At 18 weeks of age

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Infants

  Percentage of Infants With SAEs, Unsolicited AEs and AEs Leading to Study Withdrawal by a clinical examination

  At 6 months of age to assess health of the infant (phone call)

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Infants

  Percentage of Infants With SAEs, Unsolicited AEs and AEs Leading to Study Withdrawal by a clinical examination

  At 9 months of age to assess health of the infant (phone call)

• Safety Outcome: Safety assessment of Tdap vaccine vs Td vaccine in HIV-infected vs HIV-uninfected pregnant women - Infants

  Percentage of Infants With SAEs, Unsolicited AEs and AEs Leading to Study Withdrawal by a clinical examination

  At 12 months of age to assess health of the infant (phone call)

Secondary Outcomes (5)

• Anti-PT and anti-FHA IgG concentrations in HIV-infected and HIV-uninfected pregnant women following Tdap vs Td vaccination during pregnancy (4 weeks post-vaccine & at delivery)

  4 weeks post-vaccine & at delivery

• Anti-PT IgG antibody avidity in HIV-infected and HIV-uninfected pregnant women following Tdap vs Td vaccination during pregnancy

  18 weeks of pregnancy, 4 weeks post-vaccine, at delivery

• Serum bactericidal activity in HIV-infected and HIV-uninfected pregnant women following Tdap vs Td vaccination during pregnancy

  18 weeks of pregnancy, 4 weeks post-vaccine, at delivery

• Anti-PT IgG and anti-FHA placental transfer ratios in HIV-infected and HIV-uninfected pregnant women following Tdap vs Td vaccination during pregnancy

  18 weeks of pregnancy, 4 weeks post-vaccine, at delivery

• Tetanus Toxoid antibody responses in HIV-infected and HIV-uninfected pregnant women following Tdap vs Td vaccination during pregnancy

  18 weeks of pregnancy, 4 weeks post-vaccine, at delivery

Study Arms (4)

Pregnant women not living with HIV, Td vaccine

ACTIVE COMPARATOR

Biological: Standard of care vaccines

Pregnant women not living with HIV, Tdap vaccine

EXPERIMENTAL

Biological: Boostagen, (BioNet-Asia)

Pregnant women living with HIV, Td vaccine

ACTIVE COMPARATOR

Biological: Standard of care vaccines

Pregnant women living with HIV, Tdap vaccine

EXPERIMENTAL

Biological: Boostagen, (BioNet-Asia)

Interventions

Standard of care vaccines BIOLOGICAL

Visit 1: Check tetanus immunisation status. Vaccination up to 25+ 6 weeks of pregnancy with Td; Visit 2: vaccination at least 4 weeks after visit 2 with either Tdap or Td (per randomisation and according to WHO guidance)

Pregnant women living with HIV, Td vaccine; Pregnant women not living with HIV, Td vaccine

Boostagen, (BioNet-Asia) BIOLOGICAL

Visit 1: Check tetanus immunisation status. Vaccination up to 25+ 6 weeks of pregnancy with Td; Visit 2: vaccination at least 4 weeks after visit 2 with either Tdap or Td (per randomisation and according to WHO guidance);

Pregnant women living with HIV, Tdap vaccine; Pregnant women not living with HIV, Tdap vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be a woman aged 18 years or older, inclusive at day of signing the ICF;
• Pregnant woman at \>16 and \<26 weeks gestation, verified by ultrasound scan;
• Documented HIV test during pregnancy taken by rapid test at the screening visit;
• Low risk, singleton pregnancy, as assessed by the study physician based on ultrasound scan and previous obstetric history; and
• The woman is willing to comply with the study procedures, including giving birth at Kawempe National Referral Hospital, remaining in the study area until the infant is 1 year old and is able to provide informed consent for herself and on behalf of the infant

You may not qualify if:

• Any of the following:
• Previous anaphylaxis to any component of Td or Tdap vaccines;
• vaccination is otherwise contraindicated (per product monographs);
• Documented to have received four or more previous tetanus toxoid vaccine doses (as this would prevent randomisation to Tdap group and receipt of two additional tetanus toxoid containing vaccines);
• History of pre-eclampsia or eclampsia in previous pregnancies;
• Gestational diabetes in current pregnancy;
• Rhesus negative mothers;
• Multigravida;
• Previous late stillbirth (defined as loss of pregnancy at any time after 28 weeks gestation);
• Previous low birth weight baby of less than 2.0 kilograms or premature delivery (defined as a delivery before 37 weeks gestation);
• Previous neonatal death (defined as death of an infant within the first 28 days of life);
• Previous delivery of an infant with a known or suspected genetic or chromosomal abnormality;
• History of other significant pregnancy related complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected;
• History of other significant neonatal complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected;
• Significant maternal chronic illness including but not limited to hypertension requiring treatment, heart disease, lung disease, neurological disorders including a history of epilepsy or recurrent afebrile seizures, kidney disease, liver disease, anaemia and other haematological disorders (including sickle cell), endocrine disorders including known diabetes mellitus, autoimmunity;

Sponsors & Collaborators

• St George's, University of London: lead
• Medical Research Council: collaborator
• University of British Columbia: collaborator
• Public Health England: collaborator
• MU-JHU CARE: collaborator
• BioNet-Asia: collaborator

Study Sites (1)

MUJHU Care Ltd

Kampala, Uganda

Location

Related Publications (1)

• Nakabembe E, Greenland M, Amaral K, Abu-Raya B, Amone A, Andrews N, Cantrell L, Lesne E, Gorringe A, Halkerston R, Mcstraw N, Dixon L, Hunter OF, Heath PT, Imede E, Kyohere M, Musoke P, Nakimuli A, Sekikubo M, Taylor S, Tusubira V, Sadarangani M, Le Doare K. Safety and immunogenicity of an acellular pertussis vaccine containing genetically detoxified pertussis toxin administered to pregnant women living with and without HIV and their newborns (WoMANPOWER): a randomised controlled trial in Uganda. Lancet Glob Health. 2025 Jan;13(1):e81-e97. doi: 10.1016/S2214-109X(24)00409-1.

  PMID: 39706666 DERIVED

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 Officials

• Kirsty Le Doare, MBBS, PhD

  St George's, University of London

  STUDY CHAIR

• Manish Sadarangani, MRCPCH, DPHIL, BM.BCh, MA

  BC Children's Hospital Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study nursing staff and participants will be blinded to the vaccine given and vaccine syringes will be covered with an opaque label, obscuring the vaccine. Only the preparing pharmacist will be aware of the vaccine used. A study nurse who is blinded to the vaccine given will observe for immediate reactions to the vaccine in a separate room from where the woman will receive her vaccination. This room will have an emergency trolley with appropriate drugs available should these be required. The laboratory-based research team conducting the assays will be blinded to subject allocation.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will take a 2x2 formation, with four groups: 1. HIV-uninfected women, standard of care vaccines in pregnancy; 2. HIV-uninfected women, Tdap vaccine in pregnancy; 3. HIV-infected women, standard of care vaccines in pregnancy; 4. HIV-infected women, Tdap vaccine in pregnancy.

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 19, 2020
• Study Start: October 21, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)