Maternal Immunization With MenAfriVac™

NCT03746665 | Unknown Phase 3 DMC

• 1 other identifier: SCC 1585
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Meningitis; Meningococcal

Keywords

Men A; Maternal; Systems Immunology; Vaccination

Outcome Measures

Primary Outcomes (28)

• Meningococcal serogroup A (Men A) serum bactericidal activity (SBA) Geometric Mean Titre (GMT)

  Infants at birth

• Men A SBA GMT

  Infants at 8 weeks of age

• Men A SBA GMT

  Infants at 20 weeks of age

• Men A SBA GMT

  Infants at 9 months of age

• Percentage tetanus toxoid seroprotection

  Infants at birth

• Number of serious adverse events (SAE) in expectant mothers

  Between 28 to 34 weeks gestation until 8 weeks from the end of pregnancy

• Number of SAE in infants

  From birth until 9 months of age

• Injection site pain in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Injection site pain in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Injection site tenderness in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Injection site tenderness in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Injection site erythema in mothers

  Diameter of erythema in millimetres

  Day 1 to day 7 following vaccine administration

• Injection site erythema in infants

  Diameter of erythema in millimetres

  Day 1 to day 7 following vaccine administration

• Injection site induration in mothers

  Diameter of induration in millimetres

  Day 1 to day 7 following vaccine administration

• Injection site induration in infants

  Diameter of induration in millimetres

  Day 1 to day 7 following vaccine administration

• Axillary temperature in mothers

  Degrees Centigrade

  Day 1 to day 7 following vaccine administration

• Axillary temperature in infants

  Degrees Centigrade

  Day 1 to day 7 following vaccine administration

• Vomiting in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Vomiting in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Diarrhoea in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Diarrhoea in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Headaches in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Reduced feeding in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Fatigue in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Drowsiness in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Myalgia in mothers

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Irritability in infants

  Grade 0 to 5 severity

  Day 1 to day 7 following vaccine administration

• Pregnancy outcome

  Late pregnancy loss, early stillbirth, late stillbirth, livebirth

  At delivery (approximately 40 weeks gestation)

Secondary Outcomes (15)

• Men A immunoglobulin G (IgG) Geometric Mean Concentrations (GMC)

  Infants at birth

• Men A GMC

  Infants at 8 weeks of age

• Men A GMC

  Infants at 20 weeks of age

• Men A GMC

  Infants at 9 months of age

• Men A SBA GMT

  Mothers at 28 to 34 weeks gestation

Study Arms (2)

meningococcal serogroup A conjugate

EXPERIMENTAL

mothers will be vaccinated with meningococcal serogroup A conjugate vaccine between 28 - 34 weeks gestation

Biological: meningococcal serogroup A conjugate vaccine

control

NO INTERVENTION

serological samples from 100 control mother-infant pairs already recruited as part of the PROPEL trial, (SCC1433), NCT02628886

Interventions

meningococcal serogroup A conjugate vaccine BIOLOGICAL

Once final eligibility has been confirmed by a study clinician on the day, expectant mothers will be administered a single intramuscular dose of MenAfriVac™.

Also known as: MenAfriVac™.

meningococcal serogroup A conjugate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: pregnant women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Public Health England: collaborator
• Department of State for Health and Social Welfare, The Gambia: collaborator
• World Health Organization: collaborator
• University of Cambridge: collaborator
• Stanford University: collaborator

Study Sites (1)

Medical Research Council Unit (MRC), The Gambia

Fajara, The Gambia

Location

MeSH Terms

Conditions

Meningitis

Interventions

MenAfriVac

Condition Hierarchy (Ancestors)

Neuroinflammatory Diseases; Nervous System Diseases

Study Officials

• Ed Clarke, MBChB

  MRC @ LSHTM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: November 20, 2018
• Study Start: December 19, 2018
• Primary Completion: October 12, 2020
• Study Completion: August 1, 2021
• Last Updated: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)