Evaluation of Efficacy and Safety of VPM1002 in Comparison to BCG in Prevention of Tb Infection in Infants

A Multicenter, Phase III, Double-blind, Randomized, Active-controlled Study to Evaluate the Efficacy and Safety of VPM1002 in Comparison to BCG in Prevention of Mycobacterium Tuberculosis Infection in Newborn Infants

The trial is designed as a phase III, double-blind, multicenter, randomized, single administration, active-controlled, parallel-group design with two groups of newborn infants receiving either VPM1002 or BCG SII (1:1 allocation) to assess the efficacy, safety and immunogenicity of VPM1002 against Mtb infection.

The trial is designed as a phase III, double-blind, multicenter, randomized, single administration, active-controlled, parallel-group design with two groups of newborn infants receiving either VPM1002 or BCG SII (1:1 allocation) to assess the efficacy, safety and immunogenicity of VPM1002 against Mtb infection.

Healthy male or female newborn infants will be centrally randomized to receive the allocated vaccine, stratified by the HIV status of the mother. Single dose of VPM1002 or BCG SII will be administered (within 14 days of birth) strictly intradermally.

Inclusion Criteria:

A Maternal

1. Age: 18 years or older at screening.
2. Willing to comply with the trial protocol, available and willing to allow her child to complete all the trial assessments and must have signed an Informed Consent form that has been approved by respective Site Ethics Committee.
3. No symptoms or signs of active TB at the time of participant's enrolment.
4. Parent / guardian who intends to remain in the trial area with the child should be reachable by phone during the trial period.
5. For HIV-unexposed group: Test negative for HIV within two months prior to the newborn infant's vaccination. Test result must be documented, in absence of which a HIV test must be performed at the infant screening visit.
6. For the HIV-exposed group: Test positive for HIV and test result must be documented. If documentation is missing, a HIV test must be performed at the screening visit. The newborn infant's mother must have enrolled for standard antiretroviral therapy (ART) at least 2 months before the participant's birth
7. No participation in an interventional clinical trial within 3 months prior to the participant's birth. In addition, if mother is breast-feeding then she must not participate in another clinical trial during the current trial period while breastfeeding.

B Infant

1. Healthy male or female newborn infant.
2. Birth weight of at least 2,300 g.
3. Test negative for HIV by PCR at screening if born to an HIV-infected mother.
4. No participation in an interventional clinical trial prior to enrolment. Participant should not take part in another clinical trial for the duration of the current trial period.

Exclusion Criteria:

A Maternal

1. Any reported or suspected substance abuse during pregnancy.
2. House-hold contact with active TB (defined as residing in the same house as an individual with active TB) within the 3 months prior to enrolment.

B Infant

1. Fever at the time of enrolment.
2. Eczema or other significant skin lesion or infection at the site/s of injection as per protocol.
3. Receipt of routine BCG vaccine (as per vaccination record).
4. Clinically suspected sepsis.
5. Clinically suspected sepsis.
6. Any malignant condition.
7. Any clinically significant severe congenital malformation, which may interfere with the evaluation of the safety, efficacy or immunogenicity of the vaccine.
8. Concomitant treatment with medication that may significantly affect immune function (e.g. systemic corticoids, immunosuppressive drugs) before trial vaccination. (Note: Routine medication given at birth such as topical antibiotics for eye care and vitamins A and K are permitted. In HIV-exposed newborn infants prevention of mother-to-child transmission (PMTCT) based on standard of care is allowed, but must be documented.)
9. Receipt of blood products or immunoglobulin before trial vaccination.