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

• ClinicalTrials.gov Identifier: NCT04596878
• Recruitment Status: Completed
• First Posted: October 22, 2020
• Last Update Posted: August 23, 2023
• Sponsor: Minervax ApS
• Collaborator: European and Developing Countries Clinical Trials Partnership (EDCTP)
• Information provided by (Responsible Party): Minervax ApS

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Group B Streptococcal Infection	Biological: GBS-NN/NN2; Biological: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomised, placebo controlled, double-blind, parallel group, multicentre study.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: November 19, 2020
• Actual Primary Completion Date: May 18, 2022
• Actual Study Completion Date: May 11, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Biological: GBS-NN/NN2; GBS-NN/NN2 bound to Alhydrogel as an adjuvant.
Placebo Comparator: 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	Biological: Placebo; Normal Saline 0.9%
Experimental: 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	Biological: GBS-NN/NN2; GBS-NN/NN2 bound to Alhydrogel as an adjuvant.
Placebo Comparator: 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	Biological: Placebo; Normal Saline 0.9%

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment emergent adverse events [ Time Frame: From vaccination up to delivery/birth ]
   Adverse events
2. Gestational age of newborn baby [ Time Frame: At birth ]
   Gestational age of newborn baby
3. Weight of newborn baby [ Time Frame: At birth ]
   Weight of newborn baby
4. Length of newborn baby [ Time Frame: At birth ]
   Length of newborn baby
5. Head circumference of newborn baby [ Time Frame: At birth ]
   Head circumference of newborn baby
6. Apgar score for newborn baby [ Time Frame: At birth ]
   Apgar score for newborn baby
7. IgG (Immunoglobulin G) antibody concentration [ Time Frame: At birth ]
   IgG antibody concentration specific to the GBS-NN/NN2 vaccine measured in maternal blood and cord blood

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Participants at least 18 years old and not older than 40 years of age.

2. 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:

   1. ultrasound estimate of gestational age,
   2. date of last menstrual period
   3. fundal height
3. 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.
4. Women living with HIV, HIV viral load <1000, on antiretroviral therapy for at least 3 months prior to screening and clinically well.
5. 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:

1. Women who are HBSAg and/or HCV (hepatitis C virus) positive
2. Women who test positive for syphilis as per standard testing
3. Women knowingly carrying, at screening, a malformed or genetically abnormal foetus based on ultrasound
4. Women who have experienced a previous stillbirth prior to going into labour
5. Women with placenta previa
6. Women with documented chronic or pregnancy induced hypertension at screening
7. 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
8. Women with >1+ of protein in urine (regardless of blood pressure)
9. Women with gestational, type 1 or type 2 diabetes.
10. Women with glycosuria on dipstick
11. 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.
12. Women with HIV viral load >1000 at screening.
13. 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.)
14. 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.
15. Women with current or history of drug or alcohol abuse within the last two years.
16. 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.)
17. 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.
18. Women who have any bleeding disorders that prolong the bleeding time.
19. Women who are receiving immunosuppressive medication, including systemic steroids (inhaled and topical steroids are acceptable).
20. Women who have received blood or blood products and/or plasma derivatives or any immunoglobulin preparations in 12 weeks preceding screening.
21. Women with severe anaemia, haemoglobin < 9g/dL (90 g/L) as per Sheffield grading system ( > Grade 1)
22. Women who are currently breast feeding
23. Women who are part of the study personnel or a close family member of study personnel.
24. Women who in the opinion of the investigator are not suitable to participate in the study.
25. Concurrent participation in another clinical trial during which subject will be exposed to an investigational product .

Contacts and Locations

Locations

South Africa

Empilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital

Johannesburg, South Africa

University of the Witwatersrand, Johannesburg (Respiratory and Meningeal Pathogens Research unit)

Johannesburg, South Africa

Uganda

MUJHU Research Collaboration/MUJHU Care Ltd, Kawempe National Referral Hospital

Kawempe, Uganda

Sponsors and Collaborators

Minervax ApS

European and Developing Countries Clinical Trials Partnership (EDCTP)

Investigators

• Study Director: Geoff Kitson; gkitson@propharmapartners.uk.com

More Information

• Responsible Party: Minervax ApS
• ClinicalTrials.gov Identifier: NCT04596878
• Other Study ID Numbers: MVX0005
• First Posted: October 22, 2020
• Last Update Posted: August 23, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections