A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial (MOTIVATION)

Inclusion Criteria:

1. Maternal participant carrying a normal singleton pregnancy at 24 (-2/+3) weeks GA at the planned time of the first trial vaccination. GA must be based upon below criteria:

   • Last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination, i.e., at or before screening.
   • First or second trimester ultrasound examination only, if LMP is unknown/uncertain.

2. Participants ≥18 to ≤49 years of age with a body mass index (BMI) of >17.5 to <40 kg/m^2 (as measured at any time during the first trimester or just prior to becoming pregnant).

3. Maternal participant having had a foetal anomaly ultrasound examination performed at ≥18 weeks GA with no significant foetal abnormalities observed can be included.

4. Maternal participant or legally acceptable representative (where required for the foetus/infant) who is willing to provide parental consent in accordance with International Council for Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and local legislation prior to the first dose.

5. Maternal participant who is willing and able to comply with scheduled visits, the investigational plan, trial procedures, and intent to deliver at a hospital or birthing facility where trial procedures can be followed and where standard of care based on country requirements can be delivered.

Exclusion Criteria:

1. Maternal participant having a history of anaphylactic reaction associated with a vaccine.

2. Maternal participant having a history of allergic reaction (e.g., rash, anaphylaxis) to any component of GBS-NN/NN2 vaccine including to aluminium hydroxide or aminoglycoside antibiotics.

3. Maternal participant having known syphilis, human immunodeficiency virus (HIV), and/or active hepatitis B virus (HBV) as assessed by serologic tests conducted during the current pregnancy (for HIV-positive maternal participants, it is acceptable that this was confirmed prior to pregnancy). Maternal participants living with an HIV viral load of <1000 copies/mL and who have been on antiretroviral therapy for at least 3 months prior to screening and are clinically stable may be included.

4. Maternal participant having a known or suspected infection during current pregnancy with toxoplasma, parvovirus B19, malaria, zika, rubella, varicella, cytomegalovirus, or genital herpes simplex, based on medical history and/or clinical presentation.

5. Maternal participant with a history of microbiologically proven invasive disease caused by GBS in the current pregnancy (e.g., isolation of GBS from a sterile site: blood, cerebrospinal fluid, or synovial fluid). This does not include asymptomatic bacteriuria or urinary tract infection unless associated with a positive blood culture.

6. Maternal participant having bleeding diathesis or a condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

7. Maternal participant having any psychiatric condition, including recent (within the past year) active suicidal ideation/behaviour that may increase the risk of trial participation or, in the investigator's judgement, make the maternal participant unsuitable for participation in the trial.

8. Participated in other trials involving investigational drug(s) or devices within 28 days prior to trial entry, and/or are participating in other trials involving investigational drug(s) or devices, at trial entry or plan to (continue to) participate in other trials involving investigational drug(s) or devices during the trial.

9. Maternal participant having any lesion or tattoos at the planned injection site (at both arms) that will impair the assessment of the injection site.

10. Maternal participant knowingly carrying, at screening, a malformed or genetically abnormal foetus.

11. Maternal participant having current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the participation in and completion of the trial, including but not limited to the following:

    • Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
    • Placental abnormality.
    • Polyhydramnios or oligohydramnios.
    • Significant bleeding or blood clotting disorder.
    • Maternal participant having endocrine disorders, like untreated hyperthyroidism or untreated hypothyroidism. This also includes diabetes mellitus type 1 or 2 antedating pregnancy or gestational, if uncontrolled.
    • Maternal participant having any signs of premature labour with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth.

12. Maternal participant having had prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgement, that will increase the risk associated with the participation in and completion of the trial, including but not limited to the following:

    • Prior preterm delivery ≤34 weeks gestation.
    • Prior stillbirth or neonatal death.
    • Previous infant with a known genetic disorder or significant congenital anomaly.

13. Maternal participant having a known or suspected immunodeficiency or cancer or a family history of congenital or hereditary immunodeficiency. A maternal participant knowingly living with HIV may be included if on antiretroviral treatment for at least 3 months prior to screening, clinically stable, and with an HIV viral load of <1000 copies/mL.

14. Maternal participant having received chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first dose. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted. Receipt of corticosteroids for foetal lung maturation is permitted.

15. Maternal participant having an acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities. Example: Maternal participant with known non-well-controlled pre-existing arterial hypertension, prior to pregnancy, that, in the investigator's judgement, would make the maternal participant unsuitable for participation in the trial.

16. Maternal participant having received blood, blood products, plasma derivatives, or any immunoglobulin preparations in the 12 weeks before the first dose or plans to receive such products during the trial. Treatment with specific immunoglobulins to a rhesus negative maternal participant with a risk of incompatibility between maternal participant and foetus, is permitted.

17. Maternal participant having a known clinically significant anaemia at time of inclusion per investigator/site staff assessment.

18. Maternal participant who has received previous vaccination with any licensed or investigational GBS vaccine or planned receipt during participation in the trial (from the first to the last visit).

19. Maternal participant having received any other vaccine within 30 days of the first dose, or is planning to receive any vaccine (e.g., travel vaccines) between doses and up to 30 days after the second dose.

20. Maternal participant having current or history of drug or alcohol abuse, as judged by the investigator.

21. Infant participant will be a ward of the state or be released for adoption.

22. Infant participant has planned umbilical cord blood banking and/or donation.

23. Maternal participant having a pregnancy considered high risk by the investigator.

24. Any personnel involved in the conduct of the trial (and their family members), including but not limited to, site staff members, MinervaX ApS employees, and any vendor or contract research organisation (CRO) employees.