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

• ClinicalTrials.gov Identifier: NCT05154578
• Recruitment Status: Recruiting
• First Posted: December 13, 2021
• Last Update Posted: March 2, 2022
• Sponsor: Minervax ApS
• Information provided by (Responsible Party): Minervax ApS

Study Description

Brief 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).

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

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 270 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomized to one of 5 groups
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: February 17, 2022
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Normal saline

Outcome Measures

Primary Outcome Measures :

1. Concentrations of Immunoglobulin (Ig) G antibodies specific to the AlpN proteins in μg/mL in cord blood from each baby [ Time Frame: Delivery ]
   Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in cord blood from each baby

Secondary Outcome Measures :

1. Injection site reactions in the mother [ Time Frame: To Day 84 ]
   Number of participants with solicited injection site reactions following vaccination
2. Adverse events following the vaccinations in the mother [ Time Frame: To Day 84 ]
   Number of participants with solicited and other adverse events following the vaccinations
3. Clinically significant abnormal laboratory tests in the mother [ Time Frame: To Day 84 ]
   Number of participants with clinically significant abnormal laboratory tests in the mother
4. Clinically significant changes in vital signs in the mother [ Time Frame: To Day 84 ]
   Number of participants with clinically significant changes in vital signs (heart rate,blood pressure, oral temperature) in the mother
5. Clinically significant changes in physical examination in the mother [ Time Frame: To Day 84 ]
   Number of participants with clinically significant changes in physical examination in the mother
6. Gestational weight in the baby [ Time Frame: Delivery, 28 days, 90 days and 180 days post delivery. ]
   Gestational weight in the baby
7. Weight in the baby [ Time Frame: Delivery, 28 days, 90 days and 180 days post delivery. ]
   Weight in the baby
8. Length in the baby [ Time Frame: Delivery, 28 days, 90 days and 180 days post delivery. ]
   Length in the baby
9. Head circumference in the baby [ Time Frame: Delivery, 28 days, 90 days and 180 days post delivery. ]
   Head circumference in the baby
10. Apgar score in the baby [ Time Frame: 1, 5 and 10 minutes ]
    Apgar score in the baby, range 0 to 10 where high scores are good and low scores are bad
11. Developmental milestones in the baby using Ages & Stages questionnaire [ Time Frame: 6 months ]
    Developmental milestones in the baby using Ages & Stages questionnaire
12. Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in maternal blood [ Time Frame: Delivery ]
    Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in maternal blood
13. Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in blood from each baby [ Time Frame: 1 month, 3 months ]
    Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in blood from each baby

Other Outcome Measures:

1. Opsonophagocytic killing assay (OPKA) titres [ Time Frame: Delivery ]
   OPKA titres in cord blood and maternal blood
2. Concentrations of IgG antibodies specific to the NN and NN2 fusion proteins in maternal blood [ Time Frame: 4 weeks after each dose; at delivery ]
   Concentrations of IgG antibodies specific to the NN and NN2 fusion proteins in maternal blood
3. Concentrations of IgG and IgA antibodies specific to the AlpN proteins in colostrum and in breast milk [ Time Frame: Within 48 hours of delivery; 1 month and 3 months post-delivery ]
   Concentrations of IgG and IgA antibodies specific to the AlpN proteins in colostrum and in breast milk

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy pregnant woman above the legally defined age of consent at the time of screening
2. Approximately 20(±1) weeks gestation at screening and carrying a normal singleton pregnancy
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

Contacts and Locations

Contacts

Contact: Per Fisher, PhD; +45 2025 2038; pbf@minervax.com

Contact: Birgit Thierry-Carstensen, M.Sc.; +45 2683 8437; btc@minervax.com

Locations

Denmark

Hvidovre University Hospital; Recruiting

Copenhagen, Denmark

Principal Investigator: Anette Kjaerbye-Thygesen, MD

Aarhus University Hospital; Recruiting

Skejby, Denmark

Principal Investigator: Rikke Helmig, MD

United Kingdom

St George's University Hospital; Not yet recruiting

London, United Kingdom, SW17 OQT

Principal Investigator: Paul Heath, MD

University Hospital Southampton; Not yet recruiting

Southampton, United Kingdom, SO16 6YD

Principal Investigator: Christine Jones, MD

Sponsors and Collaborators

Minervax ApS

Investigators

• Study Director: Geoff Kitson, BMBS MFPM; ProPharma Partners Limited

More Information

• Responsible Party: Minervax ApS
• ClinicalTrials.gov Identifier: NCT05154578
• Other Study ID Numbers: MVX0004
• First Posted: December 13, 2021
• Last Update Posted: March 2, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• 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