Study of 4 regimens of Group B Streptococcus vaccine (GBS-NN/NN2) in pregnant women

A multicentre, multinational, parallel group, observer-blind, randomised, placebo-controlled study on the Group B Streptococcus vaccine (GBS NN/NN2), investigating the immunogenicity and safety of four vaccination regimens in pregnant woman, assessing IgG specific to AlpN proteins in cord blood and maternal blood, and the safety profile in mother and infant up to 6 months post-delivery.

Open to Recruitment

Aim of the study

Group B Streptococcus (GBS) is a type of bacteria that many people carry in their bodies. A pregnant woman may transfer GBS to her baby in the womb or during delivery. GBS generally lives in the body of healthy adults without causing harm, but it can cause severe, potentially fatal infections in babies such as meningitis (infection of the lining covering the brain and spinal cord) and pneumonia (lung infection). GBS in pregnant women can also lead to poor growth of the baby in the womb, early delivery of the baby, miscarriage, or stillbirth.

The purpose of this study is to evaluate the safety and a new vaccine (called GBS-NN/NN2) to prevent the problems caused by GBS. It is given as an intramuscular injection to women while they are pregnant.

Two studies have been completed in non-pregnant women aged 18 to 40 years: one study of this vaccine in 60 women and one study in 240 women of an earlier version of the vaccine with 2 (rather than 4) of the GBS proteins. In these studies, strong immune responses were seen when vaccinating with the same dose as being given in this study. The vaccine appeared safe and well tolerated in these studies. Side effects occurring at the vaccine injection site (such as pain, redness, bruising, swelling, or itching) were common but were generally mild to moderate and lasted only a short time. No other side effects were observed.

A study in pregnant women is currently being performed in South Africa. Safety information is available so far from 140 pregnant women who have been vaccinated and from 95 new-born babies. An independent safety review committee have reviewed the data from the first 125 women and did not identify any safety concerns.

Inclusion criteria

  • Healthy pregnant woman above the legally defined age of consent at the time of screening
  • Approximately 20(±1) weeks gestation at screening and carrying a normal singleton pregnancy
  • Properly informed about the study and has given written informed consent and parental consent (for her baby) in accordance with ICH GCP and local legislation prior to the first study intervention
  • Grants access to her own and her baby’s study related medical record

Exclusion criteria

  • Previous vaccination with an investigational Group B Streptococcus (GBS) Vaccine
  • BMI of 40 at the time of screening
  • HIV, HBV and/or HCV positive or positive for syphilis
  • Knowingly carrying, at screening, a malformed or genetically abnormal foetus, incl. renal pelvis dilation, single umbilical artery (screening will be undertaken after the ultrasound conducted for the detection of anomalies)
  • Chronic or pregnancy induced hypertension at screening, >1+ protein in urine regardless of blood pressure or 1+ protein in urine and hypertension
  • Experienced a previous stillbirth prior to going into labour
  • Gestational, type 1 or type 2 diabetes
  • Potential placenta previa as per malformation ultrasound scan
  • Rhesus negative and has anti-D antibodies or other potential harmful antibodies
  • Known or suspected allergies to any components of the vaccine including to aluminium or aminoglycoside antibiotics, or an allergic reaction related to a previous vaccination
  • Fever (temperature >37.9°C) on the day of receiving the first dose or an acute infection in the 7 days before the first dose (the first dose can be delayed if gestational age permits)
  • Received systemic steroids in the 6 weeks before the first dose (inhaled and topical steroids are acceptable)
  • Any lesion (including tattoos) at the planned injection site that will impair the assessment of the injection site
  • Received immunosuppressive medication, chemotherapy or radiotherapy in the 24 weeks before the first dose
  • Received blood, blood products, plasma derivatives or any immunoglobulin preparations in the 12 weeks before the first dose
  • Anaemia, haemoglobin (<10g/dL, 100g/L, 6.2 mmol/L)
  • Currently breast feeding
  • Received any investigational medicinal product or vaccine in the 12 weeks or 5 half-lives before the first dose
  • Received an approved vaccine within the 4 weeks before the first dose or expects to receive an approved vaccine during the study. Routine vaccinations recommended during pregnancy (e.g., pertussis and influenza) are permitted but every effort should be made to separate routine vaccinations from the trial vaccinations by at least 7 days
  • Known or suspected immunodeficiency or cancer (leukaemia, lymphoma), or a family history of congenital or hereditary immunodeficiency
  • History or presence of uncontrolled cardiovascular disease, pulmonary, hepatic, gall bladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, psychiatric, or autoimmune disease
  • History of, or current drug or alcohol abuse
  • In the opinion of the investigator not suitable for inclusion in the study
  • The pregnancy is considered high risk by treating physicians

What does participation in this study involve?

If you decide to participate, you will need to visit the study doctor 8 times to undergo study procedures and to provide information about your health. Once your child has been born, they will also attend study visits (4 visits to the study doctor) to undergo study procedures. You will also speak to the study doctor 3 times to inform them about your health.

If you decide to participate, your/your child’s GP (general practitioner) will also be notified of your participation in this study.

You will be in this study for up to 12 months.

A list of the procedures that will be completed during the study (including screening) for you and/or your child when he/she is born are included in the Participant Information Sheet.