A Multi-centre Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of a Group B Streptococcus Vaccine (GBS-NN/NN2) in Women Who Are Pregnant and Living With HIV and Women Who Are Pregnant and do Not Have HIV
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Minervax ApS
- 入组人数
- 200
- 试验地点
- 3
- 主要终点
- Incidence of treatment emergent adverse events
研究概览
简要总结
A randomised, placebo-controlled, double-blind study to evaluate the safety, tolerability and immunogenicity of the GBS-NN/NN2 (Recombinant protein vaccine against Group B Streptococcus) vaccine in women living with HIV and women without HIV, and their newborn babies from vaccination up to delivery/birth. Mothers and babies will be followed up for 12 months post-delivery.
详细描述
100 women who are pregnant and living with HIV will randomly receive two 0.5 mL (millilitre) intramuscular injections of GBS-NN/NN2 vaccine (80 women) or placebo (20 women).
100 women who are pregnant and do not have HIV will randomly receive two 0.5 mL intramuscular injections of GBS-NN/NN2 vaccine (80 women) or placebo (20 women).
Participants will be screened at 24 to 28 weeks gestation (Days -14 to Day -1) and the groups will be dosed in parallel. The first dose of vaccine or placebo will be administered at Day 0 and the second dose will be administered 28±2 days later. Delivery is anticipated to be approximately 10 to 14 weeks after the first dose of vaccine.
For the analysis of the immune response, the placebo groups will be combined. For safety, the placebo groups will be analysed separately and will be combined for comparison with the potential vaccine groups.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Participants at least 18 years old and not older than 40 years of age.
- •Pregnant women who are between 26 weeks and 30 weeks (inclusive) gestation on the planned day of vaccination with a singleton, uncomplicated pregnancy. Gestational age to be determined on the following hierarchal basis with guidance to the GAIA (Global Alignment of Immunisation Safety Assessment in pregnancy) criteria:
- •ultrasound estimate of gestational age,
- •date of last menstrual period
- •fundal height
- •HIV status to be based on rapid, confirmatory test, unless a documented test of the participant being sero-positive for HIV and history documented in the notes.
- •Women living with HIV, HIV viral load <1000, on antiretroviral therapy for at least 3 months prior to screening and clinically well.
- •Expected to be available for the scheduled clinic visits for the duration of the study, agree to be contacted by telephone during study participation, and is willing to give parental consent for her infant to participate in the study
排除标准
- •Women who are hepatitis B surface (HBSAg) and/or hepatitis C (HCV) positive
- •Women who test positive for syphilis as per standard testing
- •Women knowingly carrying, at screening, a malformed or genetically abnormal foetus based on ultrasound
- •Women who have experienced a previous stillbirth prior to going into labour
- •Women with placenta previa
- •Women with documented chronic or pregnancy induced hypertension at screening
- •Women with 1+ protein in urine and hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) at ≥20 weeks of gestation in a woman with a previously normal blood pressure
- •Women with >1+ of protein in urine (regardless of blood pressure)
- •Women with gestational, type 1 or type 2 diabetes.
- •Women with glycosuria on dipstick
- •Women known to be allergic to any components of the vaccine, known to be allergic to aluminium or having had an allergic reaction to any previous vaccination.
- •Women with history or presence of significant cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, psychiatric, autoimmune disease, cognitive disorder or current infection and significant illness 4 weeks prior to randomization.
- •Women with current or history of drug or alcohol abuse within the last two years.
- •Women who have received a vaccine within 28 days of receiving the first dose of GBS NN/NN2 or placebo or who expect to require vaccination during the course of the study. (Vaccines recommended for administration during pregnancy e.g. tetanus toxoid, pertussis and influenza are permitted. Administration of concurrent vaccines must not be within 7 days of investigational vaccine.)
- •Women who have a fever (axillary temperature >37.9°C) on the day of dosing or have had an acute infection in the 7 days before dosing.
- •Women who have any bleeding disorders that prolong the bleeding time.
- •Women who are receiving immunosuppressive medication, including systemic steroids (inhaled and topical steroids are acceptable).
- •Women who have received blood or blood products and/or plasma derivatives or any immunoglobulin preparations in 12 weeks preceding screening.
- •Women with severe anaemia, haemoglobin < 9g/dL (90 g/L) as per Sheffield grading system ( > Grade 1)
- •Women who are currently breast feeding
- •Women who are part of the study personnel or a close family member of study personnel.
- •Women who in the opinion of the investigator are not suitable to participate in the study.
- •Concurrent participation in another clinical trial during which subject will be exposed to an investigational product.
研究组 & 干预措施
Placebo Comparator in pregnant women who do not have HIV
2 doses of 0.5mL intramuscular injection 0.9% normal saline administered 28 days apart in pregnant women who do not have HIV
干预措施: Placebo (Biological)
GBS-NN/NN2 in pregnant women living with HIV
2 doses of 0.5mL intramuscular injection GBS-NN/NN2 containing 50 µg GBS-NN and 50 µg NN2 administered 28 days apart in pregnant women living with HIV
干预措施: GBS-NN/NN2 (Biological)
GBS-NN/NN2 in pregnant women who do not have HIV
2 doses of 0.5mL intramuscular injection GBS-NN/NN2 containing 50 µg GBS-NN and 50 µg NN2 administered 28 days apart in pregnant women who do not have HIV
干预措施: GBS-NN/NN2 (Biological)
Placebo Comparator in pregnant women living with HIV
2 doses of 0.5mL intramuscular injection 0.9% normal saline administered 28 days apart in pregnant women living with HIV
干预措施: Placebo (Biological)
结局指标
主要结局
Incidence of treatment emergent adverse events
时间窗: From vaccination up to delivery/birth
Adverse events
Gestational age of newborn baby
时间窗: At birth
Gestational age of newborn baby
Weight of newborn baby
时间窗: At birth
Weight of newborn baby
Length of newborn baby
时间窗: At birth
Length of newborn baby
Apgar score for newborn baby
时间窗: At birth
Apgar score for newborn baby
IgG (Immunoglobulin G) antibody concentration
时间窗: At birth
IgG antibody concentration specific to the GBS-NN/NN2 vaccine measured in maternal blood and cord blood
Head circumference of newborn baby
时间窗: At birth
Head circumference of newborn baby
Incidence of Treatment Emergent Adverse Events (TEAEs) in Maternal Participants
时间窗: From first vaccination (26 to 30 weeks of gestation) up to 28 days post-delivery, up to 24 weeks
Incidence of all TEAEs in maternal participants from first vaccination up to 28 days post-delivery.
Incidence of Adverse Events (AEs) in Newborn Babies
时间窗: From birth to first visit after birth (28±4 days post-delivery)
Incidence of AEs in Newborn babies From birth to first visit after birth (visit 6).
Number of Maternal Participants With Solicited Local AEs Within 7 Days After Each Study Vaccine Dose
时间窗: For 7 days after each study vaccine dose (first vaccine administered at baseline, second vaccine administered 28 days post baseline)
Number of maternal participants with solicited local AEs within 7 Days after each study vaccine dose, defined as: injection site redness, bruising, swelling, itching, pain and tenderness. Injection-site redness was graded based on measurements in centimeter (cm) as grade 0 (no visible redness), grade 1 (mild; 0-2 cm), grade 2 (moderate; 2.1-5 cm) or grade 3 (severe; \> 5 cm). Swelling was graded as grade 0 (no swelling detected), grade 1 (palpable "firmness" only), grade 2 (0-4 cm) or grade 3 (\> 4 cm). Pain at the injection site was rated on a visual analogue scale of 0 to 10, where 0 is no pain and 10 is extreme pain/worst possible pain. Bruising, itching and tenderness were categorised as either yes (present) or no (absent).
Number of Maternal Participants With Solicited Systemic AEs Within 7 Days After Each Study Vaccine Dose
时间窗: For 7 days after each study vaccine dose (first vaccine administered at baseline, second vaccine administered 28 days post baseline)
Number of maternal participants with solicited systemic AEs within 7 days after each study vaccine dose, defined as: headache, sore throat, "flu-like" symptoms, muscle aches, fever in the 72 hours post dose.
Gestational Age of Newborn Baby
时间窗: At birth
Gestational age of newborn baby
Weight of Newborn Baby
时间窗: At birth
Weight of newborn baby
Length of Newborn Baby
时间窗: At birth
Length of newborn baby
Head Circumference of Newborn Baby
时间窗: At birth
Head circumference of newborn baby
Apgar Score for Newborn Baby
时间窗: At birth
APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of newborn baby were measured at 1, 5 and 10 minutes. The APGAR score is a rapid clinical assessment tool used immediately after birth to evaluate a newborn's physical condition. It evaluates five criteria : Appearance (skin color), Pulse (heart rate), Grimace (Reflex irritability), Activity (muscle tone), Respiration (breathing effort), each category is scored 0, 1, or 2, where 2 indicates optimal function. Total score ranges from 0 to 10: 7-10: Normal / Reassuring - baby adapting well 4-6: Moderately abnormal - may need assisted breathing or additional monitoring 0-3: Low - requires immediate resuscitation and urgent intervention
Transfer Rate (Baby/Mother) of IgG Antibody Concentrations
时间窗: At delivery
For each of the specific IgG antibody concentrations, the transfer rate is defined as concentration in baby at birth/concentration in mother at delivery, expressed as a percentage.
次要结局
- Geometric mean fold increase in antibody concentration in maternal blood(From baseline to delivery)
- Proportion of mothers and newborn babies achieving vaccine specific IgG antibody concentrations(At delivery)
- Developmental milestones of babies(At 6 months)
- Geometric mean antibody concentration of cord and maternal blood(At delivery)
- Geometric mean antibody concentration(At 4 weeks post first injection and at 4 weeks post second injection)
- Incidence of significant adverse reactions in mothers(From delivery to 6 months post-delivery)
- Incidence of Significant Adverse Reactions in Mothers(From delivery to 6 months post-delivery)
- Developmental Milestones of Babies(At 6 months)
- Geometric Mean Antibody Concentration in Maternal Participants (4 Weeks)(At 4 weeks post first injection and at 4 weeks post second injection)
- Geometric Mean Antibody Concentration in Maternal Blood at 6 Months Post-delivery(6 months post-delivery)
- Geometric Mean Antibody Concentration in Infant Blood at 1, 2, and 3 Months Post-delivery(At 1, 2, and 3 months post-delivery)
- Geometric Mean Antibody Concentration in Newborns(Within 48 hours of birth.)
- Geometric Mean Antibody Concentration From Maternal Blood at Delivery(At delivery)
- Geometric Mean Fold Increase in Antibody Concentration in Maternal Blood(At 4 weeks post first injection and at 4 weeks post second injection)
- Geometric Mean Fold Increase in Antibody Concentration in Maternal Blood(Baseline (Gestational Age 26 to 30 weeks) pre-vaccination to delivery, up to 24 weeks)
- Proportion of Mothers Achieving Vaccine Specific IgG Antibody Concentrations(At delivery)
- Proportion of Newborn Babies Achieving Vaccine Specific IgG Antibody Concentrations(At birth)