Protecting From Pneumococcus in Early Life (The PROPEL Trial)

NCT02628886 | Unknown Phase 3 DMC

• 1 other identifier: SCC 1433
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Streptococcus pneumoniae is responsible for over 10 percent of death in children under five and many of these deaths occur in early infancy before the current pneumococcal schedule is effective and nearly half occur in sub Saharan Africa. The PROPEL trial will examine the effect of either a maternal or a neonatal dose of a pneumococcal conjugate vaccine on pneumococcal colonisation in the nose which can be used to measure the risk of disease in early life. 600 Expectant mothers will be randomized at between 28 and 34 weeks to a maternal group, a neonatal group or a control group in equal number (200 per group). Their subsequent born offspring will be followed up until nine months of age. Infants born from expectant mothers in the maternal and control group will receive their subsequent pneumococcal conjugate vaccination according to the national Expanded Programme on Immunisation (EPI) schedule in the Gambia at 8, 12 and 16 weeks while infants born to expectant mothers in the control group will receive the pneumococcal conjugate vaccine within 48 hours of birth and at 8 and 16 weeks of life. Randomization will be undertaken by defined un-blinded members of the clinical trial team who will be delegated for this task and who will not be involved in any other trial related procedures Pregnant women who are willing and who are identified by the staff of the government antenatal clinic as being potentially eligible according to gestation (assessed initially according to the date of the last menstrual period (LMP) - if known, or the fundal height), will be referred to a member of the clinical trial team. Those who remain interested in participation having had the details of the study explained will have basic demographic, obstetric and contact details collected and will be invited, at a time of their convenience, to the Medical Research Council (MRC) clinical trial site for the formal informed consent process to be completed. Following informed consent, pregnancy will be confirmed with a urinary pregnancy test. Initial screening (e.g. for past-obstetric history and past-medical history etc) will be undertaken at this point along with screening bloods for serology (HIV, hepatitis B and syphilis) and haematology (haemoglobin and sickle test). A dating ultrasound scan (USS) will also be undertaken by designated clinical trial staff. On completion of screening, expectant mothers who are confirmed to be eligible according to the defined inclusion and exclusion criteria will be enrolled and randomized in parallel into one of three equally sized groups mentioned above (maternal, neonatal, control). According to the group into which they have been randomized, mothers will receive a dose of PCV13 and tetanus toxoid \[maternal group\], placebo (0.9% sodium chloride) and tetanus toxoid \[control group\] or tetanus toxoid alone \[neonatal group\]. From this point on, the maternal and control groups (now 'Routine EPI Schedule') will be followed up in exactly the same way for the purposes of interventions and all endpoint assessments. Infants in the neonatal group ('Neonatal Schedule') will be followed up according to the schedule outlined. At the time of presentation to the delivery unit a blood sample for serology and malaria Rapid Diagnostic Test (RDT) and an nasopharyngeal swab (NPS) sample will be obtained prior to or shortly following delivery. Immediately following delivery a sample of cord blood will be obtained and as soon as possible an NPS sample will be taken from the newborn. Anthropometric measurements will be taken from the newborn and an examination conducted. Once there has not been any contraindication to vaccination identified, all newborns will be administered the routine EPI vaccines according to the schedule in The Gambia (BCG, Hepatitis B and OPV). Those newborns in the Neonatal group will additionally be administered a single intramuscular (IM) dose of PCV13. At two, three and four months, infants will be administered the routine EPI vaccines. Those infants in the Maternal and Control Groups (Routine EPI Schedule) will additionally receive PCV13 at eight, 12, and 16 weeks while those in the Neonatal group will receive the vaccine at eight and 16 weeks only having received the first dose at birth. All infants will additionally receive a single dose of the inactivated poliovirus vaccine (IPV) at 16 weeks in line with the routine EPI schedule in The Gambia. Following the vaccines administered to expectant mothers and following the vaccines administered at birth, home visits will be undertaken on day 1 to 6 to collect solicited local and systemic adverse (for PCV only) reactions and any unsolicited. A day 7 safety clinic visit will be conducted following the vaccines administered to expectant mothers and following the vaccines administered at birth. Infant will attend the clinical trial site for NPS and blood samples to be taken at specific time points.

Conditions

Pneumonia

Keywords

maternal and neonatal pneumococcal conjugate vaccination; pneumococcal carriage

Outcome Measures

Primary Outcomes (6)

• safety in pregnant mothers (SAE)

  SAE in expectant mothers from enrollment at 28 to 34 weeks gestation up to eight weeks from the end of the pregnancy

  from 28 weeks gestation to 8 weeks after delivery

• safety in newborns (SAE)

  SAE in infants from birth until nine months of age

  from birth until nine months of age

• safety in vaccinated pregnant women (local and systemic reactogenicity)

  Local and systemic reactogenicity within the first seven days of PCV13 administration to expectant mothers at between 28 and 34 weeks gestation

  within the first seven days from vaccination

• safety in vaccinated newborns (local and systemic reactogenicity)

  Local and systemic reactogenicity within the first seven days of PCV13 administration to newborn infants within the first week of life

  within the first seven days from vaccination

• outcome of pregnancy

  Pregnancy outcome

  from 28 weeks of gestation to delivery

• cumulative carriage acquisition rate in infants

  collection of Naso Pharyngeal Swab to assess Vaccine Type (VT) pneumococcal carriage rate

  from birth to 20 weeks of age

Secondary Outcomes (7)

• pneumococcal nasopharyngeal carriage rate of pregnant women

  at delivery and at 8 weeks after delivery

• nasopharyngeal carriage rate of infants

  form birth up to nine months of age

• pneumococcal vaccine type specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) and sero protection rates in mothers and infants

  at delivery and 8 weeks post delivery for the mothers and for the infants at birth, 8 weeks, 20 weeks and 9 months

• opsonophagocytic antibodies titres in infants

  at birth, 8 & 20 weeks of age

• polio virus type 1,2,3, Geometric Mean Titre (GMT) and hepatitis B GMC sero protection rate in infants

  at 8 weeks of age

Study Arms (3)

maternal group

EXPERIMENTAL

13-valent pneumococcal conjugate vaccine \[Prevenar13®\] (PCV13) vaccine, 0.5ml, once, stat, plus tetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV13 at 8, 12 and 16 weeks according to normal EPI vaccination in country

Biological: 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid

control group

PLACEBO COMPARATOR

placebo sterile 0.9% sodium chloride, 0.5ml, once, stat plus tetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV13 at 8, 12 and 16 weeks according to normal EPI vaccination in country

Biological: placebo 0.9% sodium chloride plus tetanus toxoid

neonatal group

EXPERIMENTAL

tetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV 13 0.5ml at birth, 8 weeks and 16 weeks

Other: tetanus toxoid

Interventions

13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid BIOLOGICAL

pregnant women will be given intramuscular PCV 13 vaccine between 28-34 weeks

Also known as: PCV13

maternal group

placebo 0.9% sodium chloride plus tetanus toxoid BIOLOGICAL

pregnant women will be given intramuscular saline injection between 28-34 weeks

Also known as: placebo

control group

tetanus toxoid OTHER

new born babies will be given PCV13 vaccine at birth

neonatal group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• 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 inclusive10\*
• Singleton pregnancy\*
• From 28 to 34 weeks11 gestation as determined by USS
• 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. Sukuta and 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 designee

You may not qualify if:

• History of pre-eclampsia or eclampsia
• History of gestational diabetes
• 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
• 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 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)\[51\]
• Known Human Immunodeficiency Virus (HIV) or hepatitis B (HBV) virus positive or found to be HIV or HBV positive during screening

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• WHO Pneumococcal Serology Reference Laboratory Institute of Child Health: collaborator
• BUGS Bioscience London Bioscience Innovation Centre 2 Royal College Street London: collaborator

Study Sites (1)

Sukuta Health Centre

Banjul, The Gambia

Location

MeSH Terms

Conditions

Pneumonia

Interventions

13-valent pneumococcal vaccine; Sodium Chloride; Tetanus Toxoid

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Toxoids; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Ed Clarke, MB

  Medical Research Council Unit, The Gambia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 11, 2015
• Study Start: March 11, 2016
• Primary Completion: February 19, 2019
• Study Completion: December 1, 2020
• Last Updated: October 23, 2020

Record last verified: 2020-10

Locations

TH (1)