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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Mycobacterium Tuberculosis Infection

Intervention / Treatment
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* Biological: VPM1002
* Biological: BCG SII


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A Maternal Age: 18 years or older at screening. 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. No symptoms or signs of active TB at the time of participant's enrolment. Parent / guardian who intends to remain in the trial area with the child should be reachable by phone during the trial period. 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. 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 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 Healthy male or female newborn infant. Birth weight of at least 2,300 g. Test negative for HIV by PCR at screening if born to an HIV-infected mother. 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 Any reported or suspected substance abuse during pregnancy. 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 Fever at the time of enrolment. Eczema or other significant skin lesion or infection at the site/s of injection as per protocol. Receipt of routine BCG vaccine (as per vaccination record). Clinically suspected sepsis. Clinically suspected sepsis. Any malignant condition. Any clinically significant severe congenital malformation, which may interfere with the evaluation of the safety, efficacy or immunogenicity of the vaccine. 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.) Receipt of blood products or immunoglobulin before trial vaccination.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VPM1002<br>Total 3470 subjects will be enrolled in VPM1002 arm. Single dose of VPM1002 will be administered. | Biological: VPM1002<br>* The active ingredient of the recombinant BCG vaccine, VPM1002 is Mycobacterium bovis A dose of 0.05 ml will be administered intradermally. Manufactured by the Serum Institute of India Pvt. Ltd., India Diluent: 1 ml of Water for injection/vial<br>|
| Active Comparator: BCG SII<br>Total 3470 subjects will be enrolled in BCG SII arm. Single dose of BCG SII will be administered. | Biological: BCG SII<br>* Commercially available BCG vaccine from Serum Institute of India Pvt. Ltd. A dose of 0.05 ml will be administered intradermally. Manufactured by the Serum Institute of India Pvt. Ltd., India Diluent: 1 ml of Sodium Chloride for injection/vial Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incident cases of QFT conversion, indicating Mtb infection |  | Minimum of 12 months and maximum of 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of TB disease in children receiving VPM1002 compared to BCG SII. Incident cases of sustained QFT conversion, indicating sustained Mtb infection. |  | 36 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial and fungal diseases