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Maternal Immunization With MenAfriVac™

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ClinicalTrials.gov Identifier: NCT03746665
Recruitment Status : Recruiting
First Posted : November 20, 2018
Last Update Posted : December 24, 2018
Sponsor:
Collaborators:
Public Health England
Department of State for Health and Social Welfare, The Gambia
World Health Organization
University of Cambridge
Stanford University
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:

The World Health Organization (WHO) recommends that infants receive a single dose of the meningococcal serogroup A-tetanus toxoid conjugate vaccine, MenAfriVac, when they reach at least 9 months of age. However, this leaves a window of susceptibility in early life when the incidence of invasive serogroup A disease, and the case fatality rate for the condition is at its highest. This study will investigate the potential role of administering the vaccine to expectant mothers at the start of the third trimester of pregnancy in order to protect their subsequent borne infants. Antibody transfer to the newborn and subsequent antibody decay will be measured. The level of protection against neonatal tetanus provided by the tetanus toxoid component of the vaccine, when compared to the routine dose of tetanus administered in pregnancy will also be assessed.

As a separate exploratory study, the follow-up of the cohort planned will also be used to investigate the effects that the development of the gastrointestinal microbiome, and any perturbations in the microbiome caused by antibiotic use, have on immune development and vaccine immunogenicity over the first 10 months of life.


Condition or disease Intervention/treatment Phase
Meningitis Meningococcal Biological: meningococcal serogroup A conjugate vaccine Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 100 eligible mother-infant pairs randomized to the control group in the PROPEL trial (SCC1433, NCT02628886) who gave consent for their samples to be used for other ethically-approved research will be chosen at random and serve as controls for this study
Masking: Single (Outcomes Assessor)
Masking Description: Laboratory personnel assessing primary and secondary serological endpoints (Men A and Tetanus Toxoid) will be blinded to group allocation (i.e. MenAfriVac Group versus Control Group).
Primary Purpose: Prevention
Official Title: Maternal Immunization With MenAfriVac™
Actual Study Start Date : December 19, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: meningococcal serogroup A conjugate
mothers will be vaccinated with meningococcal serogroup A conjugate vaccine between 28 - 34 weeks gestation
Biological: meningococcal serogroup A conjugate vaccine
Once final eligibility has been confirmed by a study clinician on the day, expectant mothers will be administered a single intramuscular dose of MenAfriVac™.
Other Name: MenAfriVac™.

No Intervention: control
serological samples from 100 control mother-infant pairs already recruited as part of the PROPEL trial, (SCC1433), NCT02628886



Primary Outcome Measures :
  1. Meningococcal serogroup A (Men A) serum bactericidal activity (SBA) Geometric Mean Titre (GMT) [ Time Frame: Infants at birth ]
  2. Men A SBA GMT [ Time Frame: Infants at 8 weeks of age ]
  3. Men A SBA GMT [ Time Frame: Infants at 20 weeks of age ]
  4. Men A SBA GMT [ Time Frame: Infants at 9 months of age ]
  5. Percentage tetanus toxoid seroprotection [ Time Frame: Infants at birth ]
  6. Number of serious adverse events (SAE) in expectant mothers [ Time Frame: Between 28 to 34 weeks gestation until 8 weeks from the end of pregnancy ]
  7. Number of SAE in infants [ Time Frame: From birth until 9 months of age ]
  8. Injection site pain in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  9. Injection site pain in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  10. Injection site tenderness in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  11. Injection site tenderness in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  12. Injection site erythema in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Diameter of erythema in millimetres

  13. Injection site erythema in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Diameter of erythema in millimetres

  14. Injection site induration in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Diameter of induration in millimetres

  15. Injection site induration in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Diameter of induration in millimetres

  16. Axillary temperature in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Degrees Centigrade

  17. Axillary temperature in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Degrees Centigrade

  18. Vomiting in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  19. Vomiting in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  20. Diarrhoea in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  21. Diarrhoea in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  22. Headaches in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  23. Reduced feeding in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  24. Fatigue in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  25. Drowsiness in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  26. Myalgia in mothers [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  27. Irritability in infants [ Time Frame: Day 1 to day 7 following vaccine administration ]
    Grade 0 to 5 severity

  28. Pregnancy outcome [ Time Frame: At delivery (approximately 40 weeks gestation) ]
    Late pregnancy loss, early stillbirth, late stillbirth, livebirth


Secondary Outcome Measures :
  1. Men A immunoglobulin G (IgG) Geometric Mean Concentrations (GMC) [ Time Frame: Infants at birth ]
    International units/millilitre

  2. Men A GMC [ Time Frame: Infants at 8 weeks of age ]
    International units/millilitre

  3. Men A GMC [ Time Frame: Infants at 20 weeks of age ]
    International units/millilitre

  4. Men A GMC [ Time Frame: Infants at 9 months of age ]
    International units/millilitre

  5. Men A SBA GMT [ Time Frame: Mothers at 28 to 34 weeks gestation ]
  6. Men A SBA GMT [ Time Frame: At delivery (approximately 40 weeks gestation) ]
  7. Tetanus Toxoid IgG GMC [ Time Frame: Infants at birth ]
    International units/millilitre

  8. Tetanus Toxoid IgG GMC [ Time Frame: Infants at 8 weeks ]
    International units/millilitre

  9. Tetanus Toxoid IgG GMC [ Time Frame: Infants at 20 weeks ]
    International units/millilitre

  10. Tetanus Toxoid IgG GMC [ Time Frame: Infants at 9 months ]
    International units/millilitre

  11. Tetanus Toxoid IgG GMC [ Time Frame: At delivery (approximately 40 weeks gestation) ]
    International units/millilitre

  12. Men A immunoglobulin A levels in breast milk [ Time Frame: 8 weeks from the end of pregnancy ]
    Units/millilitre

  13. Men A immunoglobulin G levels in breast milk [ Time Frame: 8 weeks from the end of pregnancy ]
    Unit/millilitre

  14. Number of adverse events (AE) in expectant mothers [ Time Frame: 28 to 34 weeks gestation until 8 weeks from the end of pregnancy ]
  15. Number of AE in infants [ Time Frame: From birth until 9 months of age ]


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:   pregnant women
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed/thumb-printed informed consent for trial participation obtained*
  • Pregnant woman aged between 18 and 40 years of age inclusive* (note that those over 33 years of age would not be expected to have been vaccinated in the national MenAfriVac™ campaign targeting 1 to 29 years olds in Nov/Dec 2013)7
  • Singleton pregnancy*
  • From 28 to 34 weeks gestation as determined by ultrasound scan
  • 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 clinical trial site (i.e. Faji Kunda health centres) *
  • 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*
  • History of gestational diabetes*
  • Rhesus negative multigravida who did not receive anti-D in previous pregnancies
  • Five or more previous pregnancies (grand-multigravida)
  • Previous late stillbirth (defined as loss of pregnancy at any time after 28 weeks gestation) *
  • Previous premature delivery (defined as delivery before 37 weeks gestation) *

    • Previous neonatal death (defined as death of an infant within the first 28 days of life) *

  • Previous Caesarean section*
  • Previous delivery of an infant with major congenital anomalies (see Table 7 for definition) *
  • Previous delivery of an infant with a known or suspected genetic9 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 complications in current pregnancy
  • Significant alcohol consumption 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, endocrine disorders including known diabetes mellitus, autoimmunity
  • Severe anaemia (<7.0g/dL) [35] *
  • 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 of 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 vaccination)
  • Any clinically significant signs or symptoms of acute illness, significant abnormalities in vital signs, an axillary temperature of > 37.5°C or any recorded fever (> 37.5°C) in the preceding 24 hours.
  • 2 or more symptoms (nausea/vomiting, diarrhoea, headaches, fatigue and myalgia) rated as grade 2 and clinically significant on the maternal systemic reactogenicity scale (Table 5) present at baseline on the day of vaccination

In cases on uncertainly, the clinical significance of any particular complaint will be judged by the PI, in discussion with other members of the clinical trial team. The safety of the expectant mother and unborn infant will always represent the key criteria with this regard. The basis of such decisions will be documented in the participant notes maintained by the clinical trial team.

In the case of an acute illness, including malaria, documented fever or abnormalities in vital signs, and also when 2 or more grade 2 systemic reactogenicity symptoms are present, the potential participant will not be deemed to be a screen failure and thus will not be permanently excluded from participation (unless the assessing clinician has reason be believe the problem will persist). Under these circumstances the expectant mother will be termed a temporary exclusion and will be re-screened at an appropriate interval for eligibility (a minimum of 24 hours in the case of a recorded fever and otherwise according to the clinical judgement of the clinician). If 34 weeks gestation passes during this period of observation, if any other inclusion criteria is no longer met (e.g. the potential participant reaches her 41st birthday) or if another exclusion criteria is met (e.g. the potential subject develops pre-eclampsia), the participant will be deemed to be a screen failure. Repeat serological testing for HIV, Hepatitis B and syphilis is not required at re-screening unless the PI has specific reason to believe that a potential participant's status may have changed in the interval since the original test. A repeat haemoglobin level is not required although may be undertaken if judged to be warranted on the basis of clinical assessment.


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): NCT03746665


Contacts
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Contact: Ed Clarke, MBChB 220-4495442-6 ext 4014 eclarke@mrc.gm
Contact: Ebrima K Kanteh, MD 220 4495442-6 ext 3034 ekanteh@mrc.gm

Locations
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Gambia
Medical Research Council Unit (MRC), The Gambia Recruiting
Fajara, Gambia
Contact: Ebrima Kanteh, MD    +4495443 ext 3034    ekanteh@mrc.gm   
Principal Investigator: Ed Clarke, PhD         
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Public Health England
Department of State for Health and Social Welfare, The Gambia
World Health Organization
University of Cambridge
Stanford University
Investigators
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Principal Investigator: Ed Clarke, MBChB MRC @ LSHTM

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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03746665     History of Changes
Other Study ID Numbers: SCC 1585
First Posted: November 20, 2018    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
Men A
Maternal
Systems Immunology
Vaccination
Additional relevant MeSH terms:
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Meningitis
Central Nervous System Diseases
Nervous System Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs