Protecting From Pneumococcus in Early Life -The PROPEL Trial

 

Streptococcus pneumoniae (Pneumococcus) is responsible for over 10 percent of deaths in children under five and many deaths still occur in early infancy before the current pneumococcal schedule (starting at 6 to 8 weeks of age) is effective.  Nearly half occur in sub Saharan Africa.

The study “A Randomized, Controlled, Double-blind, Phase 3 Trial to Evaluate the Effects of Maternal or Neonatal Pneumococcal Conjugate Vaccination (PCV) on Pneumococcal Carriage in Infants up to Nine Months of Age”, is funded through a joint research grant from MRC (UK), the Wellcome Trust and The Department for International Development (DFID), UK and sponsored by MRC Unit The Gambia in collaboration with the WHO Pneumococcal Serology Reference Laboratory Institute of Child Health, London, BUGS Bioscience, London  and the Social Anthropology Unit at the Institute of Tropical Medicine in Antwerp.

The main objectives of PROPEL are

  1. To examine the safety of a single dose of Prevenar13™ (PCV13) administered either antenatally to an expectant mother at between 28 and 34 weeks gestation or to a newborn infant within the first week of life
  1. To describe the effect of a single dose of PCV13 administered either to an expectant mother at between 28 and 34 weeks gestation or to the newborn infant within the first week of life on total vaccine type pneumococcal carriage acquisition in the infant from birth until 20 weeks of age

The study aims to randomize 600 pregnant women at between 28 and 34 weeks gestation.  It will commence in early March 2016 and will be led by Ed Clarke (Vaccines and Immunity theme). The clinical phase of the trial is expected to last around 2 years and  will be conducted at Sukuta and Faji Kunda health centres working alongside government midwifery and public health staff in these clinics.

New ultrasound facility to accurately date the pregnancies

New ultrasound facility to accurately date the pregnancies

Expectant women will be randomized at between 28 and 34 weeks gestation into either the maternal group in which they will receive a dose of PCV13 and tetanus toxoid vaccine or the Control group in which they will receive a dose of a Placebo and tetanus toxoid vaccine or the Neonatal group in which they will only receive tetanus toxoid vaccine. Infants whose mothers were in the neonatal group will receive a dose of PCV13 at birth and two further doses.  While infants born to mothers in the other groups will receive the routine three dose schedule in The Gambia.  Local and systemic reactions within the seven days of vaccination in mothers and newborns and all other illnesses in mothers and infants will be recorded.  To look at the effects of the vaccine on the risk of disease caused by pneumococcus infants will have carriage of the bacteria in the back of the nose monitored closely as well as a number of blood samples.

A Data Monitoring Committee (DMC) has been established to independently oversee the safety of the trial participants and the study will also be closely monitored locally.  It is conducted with the approval of The Gambia Government/MRC Joint Ethics Committee and the Medicines Control Agency is in place.

According to Dr Ed Clarke, Principal Investigator “MRCG, working with The Government of The Gambia, has undertaken a number of pivotal trials of pneumococcal and other conjugate vaccines in the past leading to their subsequent recommended introduction across sub-Saharan Africa.  More recently, the MRCG has also published key work on the herd protection (protection of the unvaccinated population) generated by the vaccines. There is a lot of interest globally in maternal vaccination as a way of protecting infants in early life from a number of different infections.  The trial we are starting should provide important data regarding the utility of this strategy for pneumococcal disease in a setting where carriage of the bacteria in the nose is exceptionally high in the first months of life.  We are also establishing a platform for further studies of this type in the future, given the potential importance of this approach to preventing disease in newborn babies.”