Study of a Group B Streptococcus Vaccine in Pregnant Women Living With HIV and in Pregnant Women Who do Not Have HIV

Study Overview
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Brief Summary
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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 6 months post-delivery.

Detailed Description
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100 women who are pregnant and living with HIV will randomly receive two 0.5 mL (millilitre) intramuscular injections of GBS-NN/NN2 vaccine (60 women) or placebo (15 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 (60 women) or placebo (15 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.

Official Title
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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

Conditions
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Group B Streptococcal Infection

Intervention / Treatment
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* Biological: GBS-NN/NN2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Women who are HBSAg and/or HCV (hepatitis C virus) 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, who are known to be allergic to aluminium or have had an allergic reaction to any previous vaccination. Women with HIV viral load >1000 at screening. Women living with HIV who have been on antiretroviral therapy for less than 3 months prior to screening. (Women who are diagnosed with HIV between screening and dosing will not be eligible.) 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 .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, placebo controlled, double-blind, parallel group, multicentre study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBS-NN/NN2 in pregnant women living with HIV<br>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 | Biological: GBS-NN/NN2<br>* GBS-NN/NN2 bound to Alhydrogel as an adjuvant.<br>|
| Placebo Comparator: Placebo Comparator in pregnant women living with HIV<br>2 doses of 0.5mL intramuscular injection 0.9% normal saline administered 28 days apart in pregnant women living with HIV | Biological: Placebo<br>* Normal Saline 0.9%<br>|
| Experimental: GBS-NN/NN2 in pregnant women who do not have HIV<br>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 | Biological: GBS-NN/NN2<br>* GBS-NN/NN2 bound to Alhydrogel as an adjuvant.<br>|
| Placebo Comparator: Placebo Comparator in pregnant women who do not have HIV<br>2 doses of 0.5mL intramuscular injection 0.9% normal saline administered 28 days apart in pregnant women who do not have HIV | Biological: Placebo<br>* Normal Saline 0.9%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | Adverse events | From vaccination up to delivery/birth | 
| Gestational age of newborn baby | Gestational age of newborn baby | At birth | 
| Weight of newborn baby | Weight of newborn baby | At birth | 
| Length of newborn baby | Length of newborn baby | At birth | 
| Head circumference of newborn baby | Head circumference of newborn baby | At birth | 
| Apgar score for newborn baby | Apgar score for newborn baby | At birth | 
| IgG (Immunoglobulin G) antibody concentration | IgG antibody concentration specific to the GBS-NN/NN2 vaccine measured in maternal blood and cord blood | At birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of significant adverse reactions in mothers | Significant adverse reactions | From delivery to 6 months post-delivery | 
| Developmental milestones of babies | Milestones assessed using ages and stages questionnaires | At 6 months | 
| Geometric mean antibody concentration | Geometric mean antibody concentration | At 4 weeks post first injection and at 4 weeks post second injection | 
| Geometric mean antibody concentration of cord and maternal blood | Geometric mean antibody concentration of cord (or newborn blood within 48 hours of birth) and maternal blood | At delivery | 
| Geometric mean fold increase in antibody concentration in maternal blood | 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 | 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 | Proportion of mothers and newborn babies achieving vaccine specific IgG antibody concentrations in maternal and cord blood samples respectively, above pre-defined arbitrary thresholds. | At delivery |