E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Group B Streptococcus infection in neonates.
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E.1.1.1 | Medical condition in easily understood language |
Prevention of Group B Streptococcus infection in newborns.
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053588 |
E.1.2 | Term | Group B streptococcus neonatal sepsis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the concentrations of IgG specific to the AlpN proteins (RibN, Alp1N, Alp2N and AlpCN) in cord blood from babies, born to women who received the GBS-NN/NN2 vaccine or placebo, according to four vaccination regimens during pregnancy, between the GBS-NN/NN2 and placebo groups: • Group 1: 2 doses GBS-NN/NN2 at 26 & 30 weeks GA • Group 2: 2 doses GBS-NN/NN2 at 22 & 26 weeks GA • Group 3: 2 doses GBS-NN/NN2 at 22 & 30 weeks GA • Group 4: 1 dose GBS-NN/NN2 at 26 weeks GA • Group 5: Placebo at 22, 26, and 30 weeks GA
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of the GBS-NN/NN2 vaccine in pregnant women from 22 (±1) weeks GA and to evaluate developmental milestones in the baby up to 6 months post-delivery. To compare the concentrations of IgG, specific to the AlpN proteins (RibN, Alp1N, Alp2N and AlpCN) in maternal blood at delivery, from women who received the GBS-NN/NN2 vaccine or placebo, according to four vaccination regimens during pregnancy, between the GBS-NN/NN2 and placebo groups . Secondary immunogenicity objectives: • To compare the concentrations of IgG specific to the AlpN proteins, in maternal blood at 4 weeks after each dose of vaccine/placebo for the different vaccination regimens • To evaluate the ratios of antibody concentrations between maternal and cord blood at delivery • To evaluate the concentrations of IgG specific to the AlpN proteins, up to 3 months post-delivery, in infant blood
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 time 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 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
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E.4 | Principal exclusion criteria |
1. Previous vaccination with an investigational Group B Streptococcus (GBS) Vaccine 2. BMI of <17 or >40 at the time of screening 3. HIV, HBV and/or 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The following primary endpoints will be evaluated, by group:, to support the primary objectives: • Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in cord blood from each baby: o The geometric mean antibody concentrations at birth will be calculated o The proportions of babies who achieve a concentration of IgG specific to the AlpN proteins above 0.1, 0.2, 0.5, 1, 2, 4 and 8 µg/mL at birth will be calculated
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time of the primary immunological analysis will be at the time of delivery, anticipated to be approximately 18 weeks (4 ½ months) from administration of the first dose at 22 weeks gestational age (GA) or 14 weeks (3½ months) from administration of the first dose at 26 weeks GA. Implementation of an early analysis of study data for the primary and key secondary endpoints available up to 72 hours after delivery (Visit 8). |
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E.5.2 | Secondary end point(s) |
The following key safety secondary endpoint(s) will be evaluated in the mother: Local and systemic reactogenicity and adverse events: • Solicited injection site reactions following the vaccinations • Solicited systemic adverse events following the vaccinations • All other adverse events following the vaccinations • Laboratory tests; urinalysis; vital signs (heart rate, blood pressure, oral body temperature); physical examinations The following key safety secondary endpoints will be evaluated in the baby: • Gestational age; weight; length; head circumference; Apgar score at 1, 5 and 10 minutes • Developmental milestones at 6 months of age The following secondary immunogenicity endpoints will be evaluated, by group and time-point: • Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in maternal blood: o The geometric mean antibody concentrations at delivery, and geometric mean concentration ratios relative to baseline will be calculated o The proportions of mothers who achieve a concentration of IgG specific to the AlpN proteins above 0.1, 0.2, 0.5, 1, 2, 4 and 8 µg/mL at delivery will be calculated o The geometric mean antibody concentrations at 4 weeks after each dose of vaccine/placebo and geometric mean concentration ratios relative to baseline will be calculated • The ratios of antibody concentrations between maternal and cord blood at delivery will be calculated The following immunogenicity endpoints will be evaluated in the baby: • Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in blood from each baby at 1 month and 3 months of age: o The geometric mean antibody concentrations at 1 month and 3 months after birth will be calculated o The proportions of babies who achieve a concentration of IgG specific to the AlpN proteins above 0.1, 0.2, 0.5, 1, 2, 4 and 8 µg/mL at 1 month and 3 months after birth will be calculated.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary safety endpoints will be evaluated in the mother and up to 6 months of age in the baby. Secondary immunological endpoints in the mother will be evaluated until delivery and in the baby will be evaluated at birth, 1 and 3 months of age. Implementation of an early analysis of study data for the primary and key secondary endpoints available up to 72 hours after delivery (Visit 8). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
South Africa |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is the completion of results for the primary and secondary immunogenicity analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |