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

Group B Streptococcal Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04596878
• Other study ID #: MVX0005
• Status: Completed
• Phase: Phase 2
• Start date: November 19, 2020
• Est. completion date: May 11, 2023

Study information

• Verified date: August 2023
• Source: Minervax ApS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: May 11, 2023
• Est. primary completion date: May 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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 .

Related Conditions & MeSH terms

• Group B Streptococcal Infection
• Streptococcal Infections

Intervention

Biological:
• GBS-NN/NN2
GBS-NN/NN2 bound to Alhydrogel as an adjuvant.
• Placebo
Normal Saline 0.9%

Locations

Country	Name	City	State
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
Uganda	MUJHU Research Collaboration/MUJHU Care Ltd, Kawempe National Referral Hospital	Kawempe

Sponsors (2)

Lead Sponsor	Collaborator
Minervax ApS	European and Developing Countries Clinical Trials Partnership (EDCTP)

Countries where clinical trial is conducted

South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events	Adverse events	From vaccination up to delivery/birth
Primary	Gestational age of newborn baby	Gestational age of newborn baby	At birth
Primary	Weight of newborn baby	Weight of newborn baby	At birth
Primary	Length of newborn baby	Length of newborn baby	At birth
Primary	Head circumference of newborn baby	Head circumference of newborn baby	At birth
Primary	Apgar score for newborn baby	Apgar score for newborn baby	At birth
Primary	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	Incidence of significant adverse reactions in mothers	Significant adverse reactions	From delivery to 6 months post-delivery
Secondary	Developmental milestones of babies	Milestones assessed using ages and stages questionnaires	At 6 months
Secondary	Geometric mean antibody concentration	Geometric mean antibody concentration	At 4 weeks post first injection and at 4 weeks post second injection
Secondary	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
Secondary	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
Secondary	Geometric mean fold increase in antibody concentration in maternal blood	Geometric mean fold increase in antibody concentration in maternal blood	From baseline to delivery
Secondary	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