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

Sponsor

Serum Institute of India Pvt. Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04351685

Collaborator

Vakzine Projekt Management GmbH (Industry)

6,940

Enrollment

Locations

Arms

60.7

Anticipated Duration (Months)

630.9

Patients Per Site

10.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Tuberculosis Infection	Biological: VPM1002 Biological: BCG SII	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6940 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The study is designed as a double-blind study.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Nov 9, 2020

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VPM1002 Total 3470 subjects will be enrolled in VPM1002 arm. Single dose of VPM1002 will be administered.	Biological: VPM1002 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
Active Comparator: BCG SII Total 3470 subjects will be enrolled in BCG SII arm. Single dose of BCG SII will be administered.	Biological: BCG SII 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

Arm

Intervention/Treatment

Experimental: VPM1002

Total 3470 subjects will be enrolled in VPM1002 arm. Single dose of VPM1002 will be administered.

Biological: VPM1002

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

Active Comparator: BCG SII

Total 3470 subjects will be enrolled in BCG SII arm. Single dose of BCG SII will be administered.

Biological: BCG SII

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

Outcome Measures

Primary Outcome Measures

Incident cases of QFT conversion, indicating Mtb infection [Minimum of 12 months and maximum of 36 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Days to 14 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre de Recherches Médicales de Lambaréné	Lambaréné		Gabon
2	Kenya Medical Research Institute / Center for Respiratory Disease Research	Nairobi		Kenya	47855-00100
3	Kenya Medical Research Institute - Center for Respiratory Disease Research	Siaya		Kenya	144
4	Empilweni Services and Research Unit (ESRU)	Johannesburg	Coronation Ville	South Africa	2093
5	Family Center for Research with Ubuntu	Cape Town		South Africa	7505
6	Mecru Clinical Research Unit	Medunsa		South Africa	0204
7	Respiratory and Meningeal Pathogens Research Unit	Soweto		South Africa	2013
8	South African Tuberculosis Vaccine Initiative	Worcester		South Africa	6850
9	Ifakara Health Institute	Dar Es Salaam		Tanzania	61665
10	Medical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicines (MRC/UVRI and LSHTM) Uganda Research Unit	Entebbe		Uganda
11	Makerere University/CISMAC	Kampala		Uganda	7062