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

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

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).

Study Overview

• Status: Completed
• Conditions: Group B Streptococcal Infection
• Intervention / Treatment: Biological: GBS-NN/NN2 Vaccine; Biological: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: 4 week dose interval; 2 doses; Participants 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 GBS- NN/NN2 at 30 (±1) weeks GA	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.; Biological: Placebo; 0.5 mL normal saline given by intramuscular injection; Other Names: Normal saline
Experimental: Group 2: early intervention; 4 week dose interval; 2 doses; Participants 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	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.; Biological: Placebo; 0.5 mL normal saline given by intramuscular injection; Other Names: Normal saline
Experimental: Group 3: early intervention; 8 week dose interval; 2 doses; Participants 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	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.; Biological: Placebo; 0.5 mL normal saline given by intramuscular injection; Other Names: Normal saline
Experimental: Group 4: single dose; Participants 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.	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.; Biological: Placebo; 0.5 mL normal saline given by intramuscular injection; Other Names: Normal saline
Placebo Comparator: Group 5: placebo; Participants will receive one injection of placebo at 22, 26 and 30 weeks (±1) GA	Biological: Placebo; 0.5 mL normal saline given by intramuscular injection; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injection site reactions in the mother	Number of participants with solicited injection site reactions following vaccination	To Day 84
Adverse events following the vaccinations in the mother	Number of participants with solicited and other adverse events following the vaccinations	To Day 84
Clinically significant abnormal laboratory tests in the mother	Number of participants with clinically significant abnormal laboratory tests in the mother	To Day 84
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
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
Gestational weight in the baby	Gestational weight in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Weight in the baby	Weight in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Length in the baby	Length in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
Head circumference in the baby	Head circumference in the baby	Delivery, 28 days, 90 days and 180 days post delivery.
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
Developmental milestones in the baby using Ages & Stages questionnaire	Developmental milestones in the baby using Ages & Stages questionnaire	6 months
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opsonophagocytic killing assay (OPKA) titres	OPKA titres in cord blood and maternal blood	Delivery
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
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

Collaborators and Investigators

• Sponsor: Minervax ApS
• Collaborators: Larix A/S
• Investigators: Study Director: Geoff Kitson, gkitson@propharmapartners.uk.com

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Actual): April 26, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections
• Other Study ID Numbers: MVX0004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No