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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Minervax ApS
- 入组人数
- 269
- 试验地点
- 10
- 主要终点
- Concentrations of Immunoglobulin (Ig) G Antibodies Specific to the AlpN Proteins in μg/mL in Cord Blood From Each Baby
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy pregnant woman above the legally defined age of consent at the time of screening
- •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
- •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
- •Grants access to her own and her baby's study related medical records
- •Exclusion Criteria
- •Previous vaccination with an investigational Group B Streptococcus (GBS) Vaccine
- •BMI of <17 or >40 at the time of screening
- •Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (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 (<10 g/dL, 100 g/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
排除标准
- 未提供
研究组 & 干预措施
Group 1: 4 week dose interval; 2 doses
Participants 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 GBS- NN/NN2 at 30 (±1) weeks GA
干预措施: GBS-NN/NN2 Vaccine (Biological)
Group 1: 4 week dose interval; 2 doses
Participants 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 GBS- NN/NN2 at 30 (±1) weeks GA
干预措施: Placebo (Biological)
Group 2: early intervention; 4 week dose interval; 2 doses
Participants 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
干预措施: GBS-NN/NN2 Vaccine (Biological)
Group 2: early intervention; 4 week dose interval; 2 doses
Participants 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
干预措施: Placebo (Biological)
Group 3: early intervention; 8 week dose interval; 2 doses
Participants 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
干预措施: GBS-NN/NN2 Vaccine (Biological)
Group 3: early intervention; 8 week dose interval; 2 doses
Participants 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
干预措施: Placebo (Biological)
Group 4: single dose
Participants 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.
干预措施: GBS-NN/NN2 Vaccine (Biological)
Group 4: single dose
Participants 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.
干预措施: Placebo (Biological)
Group 5: placebo
Participants will receive one injection of placebo at 22, 26 and 30 weeks (±1) GA
干预措施: Placebo (Biological)
结局指标
主要结局
Concentrations of Immunoglobulin (Ig) G Antibodies Specific to the AlpN Proteins in μg/mL in Cord Blood From Each Baby
时间窗: Delivery
Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in cord blood from each baby at birth.
次要结局
- Injection Site Reactions in the Mother(7 days following each injection)
- Adverse Events Following the Vaccinations in the Mother(To Day 84)
- Clinically Significant Abnormal Laboratory Tests in the Mother(To Day 84)
- Clinically Significant Changes in Vital Signs in the Mother(To Day 84)
- Clinically Significant Changes in Physical Examination in the Mother(To Day 84)
- Gestational Age(Delivery)
- Weight of the Baby(Delivery)
- Length of the Baby(Delivery)
- Head Circumference of the Baby(Delivery)
- Apgar Score in the Baby(1, 5 and 10 minutes)
- Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Blood From Each Baby(1 month, 3 months)
- Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Maternal Blood(Delivery)