Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202111682972355 Date of Approval: 29/11/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title 203, MTBVAC Protocol (referred to as MTBVAC-203)
Official scientific title MTBVAC in Newborns: Randomised, Double-blind Controlled Phase 3 Trial to evaluate the Efficacy, Safety and Immunogenicity of MTBVAC administered in healthy HIV unexposed and HIV exposed uninfected newborns in Tuberculosis-Endemic Regions of Sub-Saharan Africa
Brief summary describing the background and objectives of the trial Bacille Calmette Guérin (BCG), is currently the only licensed vaccine against TB, and protects against disseminated TB (miliary and meningitic disease) in children but provides inconsistent protection against the predominant form of pulmonary TB in other age groups. A new, improved TB vaccine is needed that is effective against all forms of TB disease in infants, children, and adults; and is safe in immune-compromised persons, including those with HIV infection. It is also essential in achieving the World Health Organization End TB goals and eliminate TB by 2050. This is a randomised, double-blind controlled phase 3 trial to evaluate the efficacy, safety, and immunogenicity of MTBVAC administered in healthy HIV unexposed (HU) and HIV exposed uninfected (HEU) newborns in tuberculosis-endemic regions of Sub-Saharan Africa. It is an active BCG controlled trial to evaluate the safety and efficacy of MTBVAC administered by intradermal route in approximately 7 120 healthy HIV uninfected neonates born to HIV uninfected (HIV unexposed HU cohort) and HIV infected mothers (HIV exposed uninfected HEU cohort) without known exposure to close/household TB Mycobacterium tuberculosis contacts. Participants will be enrolled from one site in Madagascar; one site in Senegal; and four or more sites in South Africa. The estimated study duration (first participant vaccinated to completion of data collection) is approximately 77 months. Minimum of 24 months to a maximum 72 months; or until study end in South Africa and 365 days in Madagascar and Senegal MTBVAC at a pre-selected dose level of 2.5 x 10^5 CFU, will be administered as a single intradermal dose within seven days of birth. All participants from the South African sites only will be considered for the Efficacy population. Participants will receive a single dose of MTBVAC, or BCG administered
Type of trial RCT
Acronym (If the trial has an acronym then please provide) 203 MTBVAC. Also known as MTBVAC203
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 10/01/2022
Actual trial start date 17/10/2022
Anticipated date of last follow up 28/02/2028
Actual Last follow-up date
Anticipated target sample size (number of participants) 7120
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group MTBVAC 1 (One) dose (0.05 mL) of reconstituted MTBVAC at a pre-selected dose level of 2.5 x 10^5 CFU, will be administered as a single intradermal dose within seven days of birth. MTBVAC is administered as a SINGLE intradermal dose. Study participation duration is a minimum of 24 months to a maximum 72 months; or until study end in South Africa; and 365 days in Madagascar and Senegal. Investigational Vaccine 3560
Control Group BCG SSI vaccine 1 (One) dose of 0.05 mL One SINGLE intradermal dose within seven days of birth. Study Participation Duration is a minimum of 24 months to a maximum 72 months; or until study end in South Africa; and 365 days in Madagascar and Senegal. Active Control 3560 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants must meet all of the following criteria at the time of randomization in order to be enrolled:  Male or female newborns within seven days of birth.  Written informed maternal consent, including permission to access maternal antenatal, postnatal, and infant medical records.  Infant participants and their caregivers available for trial follow-up and display the willingness and capacity to comply with trial procedures.  Newborns must be in good general health during pregnancy and delivery, as assessed by medical history and targeted physical examination.  Birth weight ≥ 2450 grams.  Apgar score at 5 minutes ≥ 7.  A maternal HIV test result (rapid test, enzyme-linked immunosorbent assay (ELISA), or Polymerase chain reaction (PCR)) taken within 30 days of delivery, or within seven days post-partum must be available and documented if HIV uninfected. If the mother is HIV infected, then she must be on antiretroviral (ARV) therapy as per in-country guidelines with a viral load of <50 copies/mL (within six months of labour).  Estimated gestational age ≥ 37 weeks.  Mother has not participated in a clinical trial within three months prior to the infant’s birth.  Mother has never participated in a TB vaccine trial before.  Infant may not participate in any other clinical trials. Participant Exclusion Criteria If any of the following criteria are met at the time of randomization the participant may not be enrolled:  Receipt of BCG vaccination prior to enrolment.  Significant antenatal, intrapartum, or postpartum complications that may affect the health of the newborn.  Skin condition, bruising or birth mark at the intended injection site.  Maternal HIV test (rapid test, ELISA, or PCR) result not available.  HIV exposed Newborn’s HIV PCR result positive or not available.  Maternal history of TB during pregnancy.  History of close/household contact with a TB patient, antenatal or postnatal, whether maternal, other family member or another household member who has not yet completed TB treatment.  Clinically suspected neonatal sepsis.  Any severe congenital malformation.  History or evidence of any systemic disease on examination, or any illness that in the opinion of the Investigator may interfere with the evaluation of the safety and immunogenicity of the vaccine. Neonatal jaundice not considered clinically significant is not an exclusion. New born: 0 Day-1 Month 0 Day(s) 7 Day(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/09/2021 SAHPRA
Ethics Committee Address
Street address City Postal code Country
Building A, Loftus Park, 2nd Floor, 402 Kirkness Street, Arcadia Pretoria 0083 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/11/2021 WHREC ie UNIVERSITY OF THE WITWATERSRAND HUMAN RESEARCH ETHICS COMMITTEE MEDICAL
Ethics Committee Address
Street address City Postal code Country
Suite 189, Private Bag X2600, Houghton Johannesburg 2041 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 11/10/2021 PharmaEthics
Ethics Committee Address
Street address City Postal code Country
123 Amkor Road, Lyttelton Manor Ext 3, Centurion Centurion 0157 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/02/2022 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room 46, Old Main Building, Groote Schuur Hospital, Observatory, 7925 Cape Town 7920 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/04/2022 Stellenbosch University Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Stellenbosch University Private Bag X1, Matieland, 7602, Stellenbosch, South Africa Stellenbosch 7602 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To demonstrate efficacy of MTBVAC against tuberculosis disease in healthy HU and HEU neonates compared to BCG The primary efficacy endpoint is the time from randomization to diagnosis of confirmed or unconfirmed TB disease and the secondary efficacy from randomization to diagnosis of confirmed TB disease.
Secondary Outcome To assess the safety and reactogenicity of MTBVAC in healthy HU and HEU newborns compared to BCG SAEs including deaths, will be collected from Study Day 0 visit to EoS for all participants
Secondary Outcome To biobank samples for (future) biomarker studies to identify immunological correlates of vaccine-induced protection and biomarkers of risk for TB disease. Future
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
SATVI South African Tuberculosis Vaccine Initiative Brewelskloof Hospital Haarlem Street Worcester 6850 South Africa
FAMCRU Family Centre for Research with Ubuntu Ward J8, 8th Floor Tygerberg Hospital, Francie van Zijl Drive Parow Valley 7505 South Africa
VIDA Vaccines and Infectious Diseases Analytics 1st Floor, Central-West Wing, Nurses Residence, Chris Hani Baragwanath Hospital, Chris Hani Road Soweto 1862 South Africa
ECF Durban International Clinical Research Site Enhancing Care Foundation Park home, King Edward VIII Hospital, Umbilo Road Durban 4001 South Africa
ECF Durban International Clinical Research Site Enhancing Care Foundation Wentworth Hospital, Sidmouth Avenue Durban 4052 South Africa
CRB EPLS Centre de Recherche Biomedicale Espoir Pour La Sante Maison des Programmes, 263, Route de la corniche BP 226 St Louis BP 226 Senegal
Institute Pasteur de Madagascar Galerie Zoom, Enceinte Cora, Ankorondrano, antananarivo 101 Ankorondrano B.P. 1274 Madagascar
FUNDING SOURCES
Name of source Street address City Postal code Country
Sponsor BIOFABRI SLU La Relva sn 36400 Porrino Pontevedra Spain
EDCTP Anna van Saksenlaan 51 The Hague 2593 HW Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor BIOFABRI S.L.U. La Relva sn 36400 Porrino Pontevedra Spain Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
UCT. University of Cape Town. Professor Mark Hatherill Rondebosch, Cape Town, 7700 South Africa Cape Town 7700 South Africa
IPM. Institut Pasteur de Madagascar. Dr Niaina Rakotosamimanana B.P. 1274, Ambatofotsikely Avaradoha 101 Antananarivo, Mad agascar Antananarivo B.P. 1274 Madagascar
CRB EPLS. Centre de Recherche Biomedicale Espoir Pour La Sante. Dr Gilles Riveau 263 Route de la Corniche- Sor- BP 226 Saint-Louis, Senegal Saint Louis BP 226 Senegal
SUN. Stellenbosch University. Professor Mark Cotton FAMCRU / J8, Tygerberg Academic Hospital, Tygerberg Cape Town 7505 South Africa
ECF. Enhancing Care Foundation NPC. Dr Moherndran Archary 16 Charles Strachan Road, Westridge, Durban, 4091 Durban 4091 South Africa
WHC. Wits Health Consortium PTY LTD. Wits VIDA . Vaccine and Infectious Diseases Analytics Research Unit. Professor Shabir Madhi Chris Hani Road, Chris Hani Baragwanath Academic Hospital, Wits-VIDA, 11th floor, Bertsham, 2013 Johannesburg 2013 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mark Hatherill mark.hatherill@uct.ac.za +27846718280 South African Vaccine Initiative, SATVI Project Office, Brewelskloof Hospital, Haarlem Street
City Postal code Country Position/Affiliation
Worcester 6850 South Africa International and National PI
Role Name Email Phone Street address
Public Enquiries Ingrid Murillo Jelsbak ingrid.murillo@biofabri.es 0034986330400 Biofabri SLU, La Relva sn 36400 Porrino
City Postal code Country Position/Affiliation
Pontevedra Spain Sponsor Trial Manager and Clinical Research Director
Role Name Email Phone Street address
Scientific Enquiries Federico Martinon Torres Federico.martinon.torres@sergas.es 0034981955373 Hospital Clinico Universitario de Santiago de Compostela Travesia da Choupana sn 15706
City Postal code Country Position/Affiliation
Santiago de Compostela Spain Scientific Advisor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported, will only be shared after deidentification (text, tables, figures, and appendices). Data may also be shared by way of publications, graphs, presentations in Congress and other forums. Study results may also be shared on websites such asClinicalTrials.gov or shared with others in the Scientific Community or International Organizations related with TB research. Study Protocol Immediately following publication, no end date. Data will be shared with anyone who wishes access to the data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information