Clinical trial NCT05154578: Immunogenicity and Safety of GBS-NN/NN2 in Pregnant Women
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Group B Streptococcal Infection
Lead sponsor: Minervax ApS
Sponsor class: OTHER
Collaborators: name: Larix A/S
First posted: 2021-12-13
Enrollment: 269
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to one of 5 groups
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Concentrations of Immunoglobulin (Ig) G Antibodies Specific to the AlpN Proteins in μg/mL in Cord Blood From Each Baby
timeFrame: Delivery
Secondary outcomes:
measure: Injection Site Reactions in the Mother
timeFrame: 7 days following each injection
measure: Adverse Events Following the Vaccinations in the Mother
timeFrame: To Day 84
measure: Clinically Significant Abnormal Laboratory Tests in the Mother
timeFrame: To Day 84
measure: Clinically Significant Changes in Vital Signs in the Mother
timeFrame: To Day 84
measure: Clinically Significant Changes in Physical Examination in the Mother
timeFrame: To Day 84
measure: Gestational Age
timeFrame: Delivery
measure: Weight of the Baby
timeFrame: Delivery
measure: Length of the Baby
timeFrame: Delivery
measure: Head Circumference of the Baby
timeFrame: Delivery
measure: Apgar Score in the Baby
timeFrame: 1, 5 and 10 minutes
measure: Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Maternal Blood
timeFrame: Delivery
measure: Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Blood From Each Baby
timeFrame: 1 month, 3 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital; Skejby
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
city: Kolding
country: Denmark
facility: Institut for Regional Sundhedsforskning
city: Johannesburg
country: South Africa
facility: ESRU Rahima Moosa Mother and Child Hospital
city: Johannesburg
country: South Africa
facility: Shandukani Research Clinic
city: Johannesburg
country: South Africa
facility: Wits Vaccines & Infectious Diseases Analytics
city: Pretoria
country: South Africa
facility: Mecru Clinical Research Unit (MeCRU)
city: Pretoria
country: South Africa
facility: Setshaba Research Centre
city: London
country: United Kingdom
facility: St George's University Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
affiliation: jdi@minervax.com
name: Jeannett Dimsits
role: STUDY_DIRECTOR
References: