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Gambia Pertussis Study (GaPs) (GaPs)

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ClinicalTrials.gov Identifier: NCT03606096
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
University of Oxford
National Institute for Public Health and the Environment (RIVM)
Radboud University
Imperial College London
University of Turku
Leiden University Medical Center
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:

Currently, there are two types of vaccines available against pertussis (whooping cough), an infectious disease of the respiratory tract that can be extremely serious in very young children.

Both have advantages and disadvantages: The acellular form (aP, mainly used in resource-rich countries) does not appear to offer as long lasting protection, but the whole cell vaccine (wP, mainly used in LMIC) appears to be generally more reactogenic. There is consensus that a "better pertussis vaccine" ought to be designed.

The GaPs trial is part of a series of clinical trials performed by the PERtussIS COrrelates of Protection Europe (PERISCOPE) Consortium, an EU-funded group of investigators which aims to generate knowledge on immune responses to pertussis. A better understanding of human biomarkers of protective immune responses to B. pertussis and its waning immunity is needed to accelerate the design and testing of new pertussis vaccines with a longer duration of protection.

This proposal describes the design and objectives of the clinical trial to be conducted in the Gambia, which is the only site in Africa involved in the consortium and involves the recruitment of 600 mother/infant pairs. Pregnant women will be randomised to receive either the usually recommended tetanus vaccination or a combination vaccine against whooping cough, diptheria, tetanus and polio. Their infants will receive either aP or wP as part of their EPI vaccines, and resulting immune responses will be characterized in detail up to the age of 9 months. The investigators will use immunological assays to investigate the functional humoral and cellular responses to pertussis in infants born to mothers who are randomized to receiving pertussis vaccine in pregnancy or not, and their infants who will receive either aP or wP vaccine.

Our research questions are:

Does vaccination against pertussis in pregnancy have impact on subsequent immune responses to pertussis vaccine and other EPI vaccines in the infants Does vaccination of infants with wP vaccine induce different levels and functionality of antibody and/or T cell responses than vaccination with aP vaccine What is the difference in innate and acquired immunity- as measured with novel systems vaccinology tools- between being vaccinated with wP versus aP?


Condition or disease Intervention/treatment Phase
Pertussis Biological: Boostrix IPV infant acellular Pertussis Biological: Boostrix IPV infant whole Pertussis Biological: TT infant acellular Pertussis Biological: TT infant whole Pertussis Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Eligible pregnant women will be randomized in parallel into one of four groups: two groups will receive maternal Boostrix ® Polio (GSK) the other two groups Tetanus toxoid as per EPI schedule.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Neither the expectant mothers themselves nor members of the clinical trial team assessing the safety or laboratory-based endpoints (immunogenicity and exploratory immunology) will be aware which of these groups the expectant mother has been randomized into.
Primary Purpose: Prevention
Official Title: Randomised, Double-blinded, Open Label Study in Pregnant Women, Exploring the Impact of Acellular Pertussis Vaccination in Pregnancy on the Immunogenicity in Infants Randomized to Receive Either an Acellular (aP) or Whole Cell Pertussis (wP) Vaccine Subsequently
Actual Study Start Date : January 23, 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Whooping Cough

Arm Intervention/treatment
Experimental: Boostrix IPV - infant acellular Pertussis (TdaP-aP)
vaccination of the mother with Boostrix-IPV vaccine which includes the infant acellular pertussis
Biological: Boostrix IPV infant acellular Pertussis
mother is randomized to receive Boostrix ® Polio (GSK) and infant acellular pertussis

Experimental: Boostrix IPV - infant whole Pertussis (Tdap-wP )
vaccination of mother with Boostrix -IPV which includes infant whole cell pertussis
Biological: Boostrix IPV infant whole Pertussis
mother is randomized to receive Boostrix ® Polio (GSK) and infant whole Pertussis

Active Comparator: TT - infant acellular Pertussis (T-ap )
vaccination of mother with TT-which includes infant acellular pertussis
Biological: TT infant acellular Pertussis
mother is randomised to receive Tetanus Toxoid and infant acellular Pertussis

Active Comparator: TT - infant whole Pertussis (T-wP)
vaccination of mother with T which includes infant whole cell pertussis
Biological: TT infant whole Pertussis
mother is randomised to receive Tetanus Toxoid and infant whole Pertussis




Primary Outcome Measures :
  1. PT specific antibody GMC [ Time Frame: 20 weeks ]
    PT-specific antibody GMC at 20 weeks in infants vaccinated with aP versus wP

  2. PT specific antibody GMC [ Time Frame: 9 months ]
    PT-specific antibody GMC at 9 months in infants vaccinated with aP versus wP


Secondary Outcome Measures :
  1. PT specific antibody [ Time Frame: at 20 weeks and 9 months ]
    PT-specific antibody GMC at 20 weeks and 9 months in infants vaccinated with aP versus wP following maternal vaccination with Boostrix ® Polio (GSK) or Tetanus Toxoid.

  2. change in PT, FHA, and PRN antibody concentrations [ Time Frame: at 8 and 20 weeks and at 9 months of age ]
    Proportion with a 2-fold reduction in PT, FHA, and PRN antibody concentrations (measured in cord blood) from baseline at 8, 20 weeks and 9 months of age in aP versus wP primed infants following maternal immunisation with Boostrix ® Polio (GSK) or Tetanus Toxoid

  3. Pertussis antigen-specific memory B-cell [ Time Frame: at 8, 16 weeks and at 9 months of age ]
    Pertussis antigen-specific memory B-cell frequencies at 8,16 weeks and 9 months of age measured by ELISpot in the aP versus wP group following maternal immunisation with aP or Boostrix ® Polio (GSK) or Tetanus Toxoid

  4. Pertussis antigen-specific Th1, Th2 and Th17 responses [ Time Frame: at 16 weeks of age of the infant ]
    Pertussis antigen-specific Th1, Th2 and Th17 responses determined by flow-cytometry and cytokine analysis following antigen-specific culture (the 'Rapid T-cell assay').

  5. PT, FHA and PRN-specific antibody GMC and GMR [ Time Frame: at baseline (cord blood baseline) and at 8, 20 weeks and at 9 months ]
    PT, FHA and PRN-specific antibody GMC and GMR prior to immunisation (cord blood baseline) and at 8, 20 weeks and 9 months of age.

  6. Hib, diphtheria, tetanus, pneumococcal and polio-specific antibody [ Time Frame: at 8, 20 weeks and 9 months ]
    Hib, diphtheria, tetanus, pneumococcal and polio-specific antibody concentrations

  7. Serious adverse events (SAE) in expectant mothers [ Time Frame: at 28-34 weeks gestation up to eight weeks from the end of pregnancy. ]
    Serious adverse events (SAE) in expectant mothers from enrollment at 28-34 weeks gestation up to eight weeks from the end of pregnancy.

  8. local and systemic reactogenicity [ Time Frame: within first 3 days of aP administration ]
    Proportion of mothers 28-34 weeks gestation with local and systemic reactogenicity within the first three days of aP administration

  9. PT specific antibody [ Time Frame: at 9 months post delivery ]
    PT-specific antibody GMC 9 months post delivery



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The study will randomize 600 pregnant women at between 28-34 weeks gestation
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • signed /thumb-printed informed consent for trial participation obtained
  • Pregnant women between 18 and 40 years of age inclusive on day of consent
  • Singleton pregnancy
  • From 28 to 34 weeks gestation inclusive as determined by USS on day of randomization.
  • Resident within easy reach of the clinical trial site (no fixed boundaries will be set and such judgements will be made on a case by case basis by members of the field team in discussion with the potential participant, taking into account knowledge of the local transport links and geography)
  • Intention to deliver at the health centre related to the Sukuta clinical trial site
  • Willingness and capacity to comply with all the study procedures, including those relating to the newborn infant, in the opinion of the principal investigator or delegee.

Exclusion Criteria:

  • History of pre-eclampsia or eclampsia
  • Gestational diabetes in current pregnancy
  • Rhesus negative multigravida
  • Grandmultigravida (more than 5 previous pregnancies)
  • Previous late stillbirth (defined as loss of pregnancy at any time after 28 weeks gestation)
  • Previous low birth weight baby 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
  • Smoke cigarettes, alcohol consumption or use of illegal drugs during current pregnancy
  • 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
  • Severe anaemia (less than 7.0g/dL)
  • Known Human Immunodeficiency Virus (HIV) or hepatitis B (HBV) virus positive or found to be HIV or HBV positive during screening
  • Positive result for syphilis infection on laboratory testing
  • Receipt of any vaccine during the current pregnancy or plans to receive any non-study vaccines during the current pregnancy (tetanus toxoid vaccination is not an exclusion and vaccines given during national campaigns if applicable will not generally be exclusions)
  • Any other condition judged to significantly increase the risks to either the mother or the infant within the current pregnancy (including relevant history from previous pregnancies)
  • History of anaphylactic or severe allergic reactions to previous vaccines or history of anaphylactic or severe allergic reactions in previous offspring (if applicable)
  • Receipt of any blood product including human immunoglobulins at any stage during the current pregnancy or plan to receive any blood products during the period or trial participation (receipt or blood products in an emergency or for obstetric reasons will not represent a protocol deviation given such situations are unplanned)
  • Receipt of immunosuppressive or immuno-modulatory medication at any stage during the current pregnancy or plan to receive any such medication during the period or trial participation
  • Clinically suspected or confirmed congenital or acquired clotting or bleeding disorders or the current receipt of medications known to alter clotting or bleeding
  • Current malaria infection (on the day of randomization and vaccination)
  • Any clinically significant signs or symptoms of acute illness, significant abnormalities in vital signs, an axillary temperature of greater than 38.0°C or any recorded fever (greater than 38.0°C) in the preceding 24 hours.
  • Two or more symptoms (nausea/vomiting, diarrhoea, headaches, fatigue and myalgia) rated as grade 2 and clinically significant on the maternal systemic reactogenicity scale (2 Table 5) present at baseline on the day of vaccination
  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized
  • involuntarily
  • Participation in the 4 weeks preceding the trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03606096


Contacts
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Contact: Beate Kampmann, MD, PhD +220-4495442-6 bkampmann@mrc.gm
Contact: Michael E Okoye, MBBS +220-4495443-6 ext 3034 mokoye@mrc.gm

Locations
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Gambia
Sukuta Health Centre Recruiting
Sukuta, Banjul, Gambia
Contact: Michael E Okoye, MBBS    220-4405443-6 ext 3034    mokoye@mrc.gm   
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
University of Oxford
National Institute for Public Health and the Environment (RIVM)
Radboud University
Imperial College London
University of Turku
Leiden University Medical Center
Investigators
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Principal Investigator: Beate Kampmann, MD, PhD MRC Unit at LSHTM

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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03606096     History of Changes
Other Study ID Numbers: SCC 1600
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by London School of Hygiene and Tropical Medicine:
immune response
impact of acellular pertussis vaccination

Additional relevant MeSH terms:
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Whooping Cough
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs