immunogenicity and safety of gbs-nn/nn2 in pregnant women

Conditions: Group B Streptococcal Infection

Summary: this is a phase ii, multicentre, multinational, randomized, parallel group, placebo-controlled study of four vaccination regimens in healthy pregnant women. there will be 5 treatment groups; three groups of 60 participants will receive will receive two doses of gbs-nn/nn2 vaccine and one dose of placebo (saline); one group of 60 participants will receive one dose of gbs-nn/nn2 vaccine and two doses of placebo (saline), and one group of 30 participants will receive three doses of placebo (saline).

this is a phase ii, multicentre, multinational, randomized, parallel group, placebo-controlled study of four vaccination regimens in healthy pregnant women. there will be 5 treatment groups; group 1 will receive one injection of placebo at 22 (±1) weeks gestational age (ga), one injection of gbs-nn/nn2 at 26 (±1) weeks ga and one injection of gbs- nn/nn2 at 30 (±1) weeks ga. group 2 will receive one injection of gbs-nn/nn2 at 22 (±1) weeks ga, one injection of gbs-nn/nn2 at 26 (±1) weeks ga and one injection of placebo at 30 (±1) weeks ga.group 3 will receive one injection of gbs-nn/nn2 at 22 (±1) weeks ga, one injection of placebo at 26 (±1) weeks ga and one injection of gbs- nn/nn2 at 30 (±1) weeks ga. group 4 will receive one injection of placebo at 22 (±1) weeks ga, one injection of gbs-nn/nn2 at 26 (±1) weeks ga and one injection of placebo at 30 (±1) weeks ga. group 5 will receive an injection of placebo at 22, 26 and 30 weeks (±1) ga. participants will attend the clinic for assessment visits up to delivery and for a further 3 visits at 28 (±4) days, 90 (±6) days and 180 (±14) days post delivery. babies will be also be assessed at delivery, and 28 (±4) days, 90 (±6) days and 180 (±14) days post delivery.

Eligibility criteria:
inclusion criteria: 1. healthy pregnant woman above the legally defined age of consent at the time of screening 2. carrying a normal singleton pregnancy, and is at 21+0 to 23+6 weeks ga at the planned tme of the 1st vaccination, as established by first/second trimester ultrasound examination 3. properly informed about the study and has given written informed consent and parental consent (for her baby) in accordance with the international conference on harmonization good clinical practice (ich gcp) and local legislation prior to the first study intervention 4. grants access to her own and her baby's study related medical records exclusion criteria 1. previous vaccination with an investigational group b streptococcus (gbs) vaccine 2. bmi of \ 40 at the time of screening 3. human immunodeficiency virus (hiv), hepatitis b virus (hbv) and/or hepatitis c virus (hcv) positive or positive for syphilis 4. 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) 5. chronic or pregnancy induced hypertension at screening, \>1+ protein in urine regardless of blood pressure or 1+ protein in urine and hypertension 6. experienced a previous stillbirth prior to going into labour 7. gestational, type 1 or type 2 diabetes 8. potential placenta previa as per malformation ultrasound scan 9. rhesus negative and has anti-d antibodies or other potential harmful antibodies 10. 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 11. 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) 12. received systemic steroids in the 6 weeks before the first dose (inhaled and topical steroids are acceptable) 13. any lesion (including tattoos) at the planned injection site that will impair the assessment of the injection site 14. received immunosuppressive medication, chemotherapy or radiotherapy in the 24 weeks before the first dose 15. received blood, blood products, plasma derivatives or any immunoglobulin preparations in the 12 weeks before the first dose 16. anaemia, haemoglobin (\<10 g/dl, 100 g/l, 6.2 mmol/l) 17. currently breast feeding 18. received any investigational medicinal product or vaccine in the 12 weeks or 5 half-lives before the first dose 19. 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. 20. known or suspected immunodeficiency or cancer (leukaemia, lymphoma), or a family history of congenital or hereditary immunodeficiency 21. 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 22. history of, or current drug or alcohol abuse 23. in the opinion of the investigator not suitable for inclusion in the study 24. the pregnancy is considered high risk by treating physicians