Dose-escalation Safety and Immunogenicity Study to Compare MTBVAC to BCG in Newborns With a Safety Arm in Adults

NCT02729571 | Completed Phase 1 DMC

• 1 other identifier: MTBVAC-02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, controlled, double blind clinical trial in 2 stages (adult stage, infant stage). The first stage includes 18 HIV uninfected, QFT negative, BCG vaccinated, adult participants, randomized 1:1 to receive BCG Vaccine SSI or MTBVAC at equivalent dose (5x10E05 CFU/0.1mL) (n=9 in each group). Upon favourable safety review by the DSMB for all 18 adults up to day 28 after study vaccination, the second stage will commence in thirty-six (36) HIV unexposed, BCG naïve, newborn infants, randomized 1:3 to receive BCG Vaccine SSI or MTBVAC at one of three different dose levels ( (n=9 in each group).

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Safety and reactogenicity in infants and adults: includes injection site and systemic and regional adverse events, solicited and unsolicited. A diary card will be for solicited local, regional, and systemic adverse event data.

  Six (6) months post-study vaccination

Secondary Outcomes (1)

• Primary immunogenicity analysis (in infants only): Measure of frequencies and co-expression patterns of CD4 and CD8 T cells expressing specific cytokines in whole blood.

  Six (6) months post-study vaccination

Study Arms (4)

MTBVAC Group 1

EXPERIMENTAL

Intervention: MTBVAC live vaccine (low dose)

Biological: MTBVAC

MTBVAC Group 2

EXPERIMENTAL

Intervention: MTBVAC live vaccine (middle dose)

Biological: MTBVAC

MTBVAC Group 3

EXPERIMENTAL

Intervention: MTBVAC live vaccine (high dose)

Biological: MTBVAC

BCG Control Group

ACTIVE COMPARATOR

Intervention: commercially available BCG live vaccine

Biological: BCG

Interventions

MTBVAC BIOLOGICAL

Live-attenuated tuberculosis vaccine

MTBVAC Group 1; MTBVAC Group 2; MTBVAC Group 3

BCG BIOLOGICAL

Commercially available live-attenuated tuberculosis vaccine

BCG Control Group

Eligibility Criteria

• Age: 1 Day - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adult stage:
• Male or female, age 18 to 50 years
• Written informed consent, including permission for access to medical records and an HIV test.
• Available for study follow up and display a willingness and capacity to comply to study procedures.
• In good general health, as assessed by medical history and a focused physical examination.
• HIV test (rapid test, ELISA, or PCR) negative
• Quantiferon®-TB Gold (Cellestis) test for latent TB infection negative within 3 weeks of enrolment
• BCG vaccination at birth as confirmed by history or the presence of a BCG scar
• In the case of female participants, a negative urine or serum pregnancy test at enrolment, not lactating, and willingness to use an acceptable method of contraception to avoid pregnancy for the duration of the study
• Infant Stage:
• Male or female neonates within 96 hours of birth.
• Written informed parental consent, including permission to access medical records and results of antenatal HIV tests.
• Infant participants and their caregivers available for study follow-up and display the willingness and capacity to comply with study procedures.
• Neonates must be in good general health as assessed by antenatal history, delivery records, and focused physical examination.
• Birth weight more than or equal to 2500 grams.

You may not qualify if:

• A history or evidence of an acute or chronic medical or surgical condition likely to affect the safety, reactogenicity, or immunogenicity of the investigational vaccine
• Skin condition, bruising or birth mark at the intended injection site.
• History or evidence of previous or current active TB disease
• History of a household contact with active TB disease who has received less than 2 months treatment
• Infant must not have received routine BCG vaccination prior to enrolment.
• Antenatal, intrapartum, or postnatal medical or surgical condition that may affect the safety, reactogenicity, or immunogenicity of the investigational vaccine.
• Maternal HIV test (rapid test, ELISA or PCR) not performed antenatally, HIV test results not available, or HIV test result known positive.
• Maternal or other household contact with newly diagnosed or incompletely treated active TB disease.

Sponsors & Collaborators

• Biofabri, S.L: lead
• South African Tuberculosis Vaccine Initiative: collaborator
• TuBerculosis Vaccine Initiative: collaborator
• Triclinium Clinical Trial Project Management (Pty) Ltd.: collaborator
• Universidad de Zaragoza: collaborator

Study Sites (1)

South African Tuberculosis Vaccine Initiative, Brewelskloof Hospital

Worcester, Western Cape, 6850, South Africa

Location

Related Publications (4)

• Spertini F, Audran R, Chakour R, Karoui O, Steiner-Monard V, Thierry AC, Mayor CE, Rettby N, Jaton K, Vallotton L, Lazor-Blanchet C, Doce J, Puentes E, Marinova D, Aguilo N, Martin C. Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial. Lancet Respir Med. 2015 Dec;3(12):953-62. doi: 10.1016/S2213-2600(15)00435-X. Epub 2015 Nov 17.

  PMID: 26598141 BACKGROUND

• Aguilo N, Uranga S, Marinova D, Monzon M, Badiola J, Martin C. MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice. Tuberculosis (Edinb). 2016 Jan;96:71-4. doi: 10.1016/j.tube.2015.10.010. Epub 2015 Nov 30.

  PMID: 26786657 BACKGROUND

• Arbues A, Aguilo JI, Gonzalo-Asensio J, Marinova D, Uranga S, Puentes E, Fernandez C, Parra A, Cardona PJ, Vilaplana C, Ausina V, Williams A, Clark S, Malaga W, Guilhot C, Gicquel B, Martin C. Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials. Vaccine. 2013 Oct 1;31(42):4867-73. doi: 10.1016/j.vaccine.2013.07.051. Epub 2013 Aug 17.

  PMID: 23965219 BACKGROUND

• Tameris M, Mearns H, Penn-Nicholson A, Gregg Y, Bilek N, Mabwe S, Geldenhuys H, Shenje J, Luabeya AKK, Murillo I, Doce J, Aguilo N, Marinova D, Puentes E, Rodriguez E, Gonzalo-Asensio J, Fritzell B, Thole J, Martin C, Scriba TJ, Hatherill M; MTBVAC Clinical Trial Team. Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial. Lancet Respir Med. 2019 Sep;7(9):757-770. doi: 10.1016/S2213-2600(19)30251-6. Epub 2019 Aug 12.

  PMID: 31416768 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

MTBVAC vaccine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Michele Tameris, MD

  South African Tuberculosis Vaccine Initiative

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: April 6, 2016
• Study Start: September 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: March 1, 2018
• Last Updated: May 1, 2018

Record last verified: 2018-04

Locations

ZA (1)