Immunogenicity and Safety of GBS-NN/NN2 in Pregnant Women

Group B Streptococcal Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05154578
• Other study ID #: MVX0004
• Status: Completed
• Phase: Phase 2
• Start date: February 17, 2022
• Est. completion date: October 18, 2023

Study information

• Verified date: March 2024
• Source: Minervax ApS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 60 participants will receive three doses of placebo (saline).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: October 18, 2023
• Est. primary completion date: April 26, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Healthy pregnant woman above the legally defined age of consent at the time of screening

2. 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

3. 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

4. Grants access to her own and her baby's study related medical records Exclusion Criteria

1. Previous vaccination with an investigational Group B Streptococcus (GBS) Vaccine

2. BMI of <17 or >40 at the time of screening

3. Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) positive or positive for syphilis

4. 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)

5. Chronic or pregnancy induced hypertension at screening, >1+ protein in urine regardless of blood pressure or 1+ protein in urine and hypertension

6. Experienced a previous stillbirth prior to going into labour

7. Gestational, type 1 or type 2 diabetes

8. Potential placenta previa as per malformation ultrasound scan

9. Rhesus negative and has anti-D antibodies or other potential harmful antibodies

10. 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

11. 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)

12. Received systemic steroids in the 6 weeks before the first dose (inhaled and topical steroids are acceptable)

13. Any lesion (including tattoos) at the planned injection site that will impair the assessment of the injection site

14. Received immunosuppressive medication, chemotherapy or radiotherapy in the 24 weeks before the first dose

15. Received blood, blood products, plasma derivatives or any immunoglobulin preparations in the 12 weeks before the first dose

16. Anaemia, haemoglobin (<10 g/dL, 100 g/L, 6.2 mmol/L)

17. Currently breast feeding

18. Received any investigational medicinal product or vaccine in the 12 weeks or 5 half-lives before the first dose

19. 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.

20. Known or suspected immunodeficiency or cancer (leukaemia, lymphoma), or a family history of congenital or hereditary immunodeficiency

21. 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

22. History of, or current drug or alcohol abuse

23. In the opinion of the investigator not suitable for inclusion in the study

24. The pregnancy is considered high risk by treating physicians

Related Conditions & MeSH terms

• Group B Streptococcal Infection
• Streptococcal Infections

Intervention

Biological:
• GBS-NN/NN2 Vaccine
0.5 mL GBS-NN/NN2 containing 50 µg of GBS-NN and 50 µg of GBS-NN2 and 0.5 mg of aluminium, given by intramuscular injection.
• Placebo
0.5 mL normal saline given by intramuscular injection

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital; Skejby	Aarhus
Denmark	Hvidovre University Hospital	Hvidovre
Denmark	Institut for Regional Sundhedsforskning	Kolding
South Africa	ESRU Rahima Moosa Mother and Child Hospital	Johannesburg
South Africa	Shandukani Research Clinic	Johannesburg
South Africa	Wits Vaccines & Infectious Diseases Analytics	Johannesburg
South Africa	Mecru Clinical Research Unit (MeCRU)	Pretoria
South Africa	Setshaba Research Centre	Pretoria
United Kingdom	St George's University Hospital	London
United Kingdom	University Hospital Southampton	Southampton

Sponsors (2)

Lead Sponsor	Collaborator
Minervax ApS	Larix A/S

Countries where clinical trial is conducted

Denmark,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Opsonophagocytic killing assay (OPKA) titres	OPKA titres in cord blood and maternal blood	Delivery
Other	Concentrations of IgG antibodies specific to the NN and NN2 fusion proteins in maternal blood	Concentrations of IgG antibodies specific to the NN and NN2 fusion proteins in maternal blood	4 weeks after each dose; at delivery
Other	Concentrations of IgG and IgA antibodies specific to the AlpN proteins in colostrum and in breast milk	Concentrations of IgG and IgA antibodies specific to the AlpN proteins in colostrum and in breast milk	Within 48 hours of delivery; 1 month and 3 months post-delivery
Primary	Concentrations of Immunoglobulin (Ig) G antibodies specific to the AlpN proteins in µg/mL in cord blood from each baby	Concentrations of IgG antibodies specific to the AlpN proteins in µg/mL in cord blood from each baby	Delivery
Secondary	Injection site reactions in the mother	Number of participants with solicited injection site reactions following vaccination	To Day 84
Secondary	Adverse events following the vaccinations in the mother	Number of participants with solicited and other adverse events following the vaccinations	To Day 84
Secondary	Clinically significant abnormal laboratory tests in the mother	Number of participants with clinically significant abnormal laboratory tests in the mother	To Day 84
Secondary	Clinically significant changes in vital signs in the mother	Number of participants with clinically significant changes in vital signs (heart rate,blood pressure, oral temperature) in the mother	To Day 84
Secondary	Clinically significant changes in physical examination in the mother	Number of participants with clinically significant changes in physical examination in the mother	To Day 84
Secondary	Gestational weight in the baby	Gestational weight in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Secondary	Weight in the baby	Weight in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Secondary	Length in the baby	Length in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Secondary	Head circumference in the baby	Head circumference in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Secondary	Apgar score in the baby	Apgar score in the baby, range 0 to 10 where high scores are good and low scores are bad	1, 5 and 10 minutes
Secondary	Developmental milestones in the baby using Ages & Stages questionnaire	Developmental milestones in the baby using Ages & Stages questionnaire	6 months
Secondary	Concentrations of IgG antibodies specific to the AlpN proteins in µg/mL in maternal blood	Concentrations of IgG antibodies specific to the AlpN proteins in µg/mL in maternal blood	Delivery
Secondary	Concentrations of IgG antibodies specific to the AlpN proteins in µg/mL in blood from each baby	Concentrations of IgG antibodies specific to the AlpN proteins in µg/mL in blood from each baby	1 month, 3 months