Dose-Escalation Study to Evaluate the Safety and Immunogenicity of MTBVAC Vaccine in Comparison With BCG Vaccine.

NCT02013245 | Completed Phase 1 Results DMC

• 1 other identifier: MTBVAC-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and immunogenicity of MTBVAC as a potential substitute for BCG vaccination. BCG vaccination has indeed demonstrated its major limitation in inducing protection against tuberculosis (TB). Novel vaccines are essential to fight against the current world epidemics in tuberculosis and resistance to anti-TB drugs.

Conditions

Tuberculosis; Healthy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events up to 210 Days After Vaccination

  Safety and reactogenicity for all subjects as determined by: * Occurrence of solicited symptoms during the 7-day follow-up period following vaccination and occurrence of unsolicited symptoms during the 210-day follow-up period following vaccination. * Occurrence of grade 3 vaccine related local and general symptoms during the 210-day follow-up period following vaccination and occurrence of serious adverse events throughout the entire study period. * Haematological and biochemical safety test levels prior and after vaccination

  7 months follow up

Secondary Outcomes (1)

• Number of Participants With Three-cytokine-positive CD4+ T-cell Response

  Day 28

Study Arms (4)

MTBVAC group 1

EXPERIMENTAL

Intervention: MTBVAC live vaccine (low dose 5 x 10E03 CFU/0.1mL)

Biological: MTBVAC live vaccine

MTBVAC Group 2

EXPERIMENTAL

Intervention: MTBVAC live vaccine (middle dose 5 x 10E04 CFU/0.1mL)

Biological: MTBVAC live vaccine

MTBVAC Group 3

EXPERIMENTAL

Intervention: MTBVAC live vaccine (high dose 5 x 10E05 CFU/0.1mL)

Biological: MTBVAC live vaccine

BCG Control Group

ACTIVE COMPARATOR

Intervention: Commercially available BCG live vaccine (dose 5 x 10E05 CFU/0.1mL)

Biological: Commercially available BCG live vaccine

Interventions

MTBVAC live vaccine BIOLOGICAL

Live-attenuated Mycobacterium tuberculosis vaccine

MTBVAC Group 2; MTBVAC Group 3; MTBVAC group 1

Commercially available BCG live vaccine BIOLOGICAL

Live-attenuated Mycobacterium bovis vaccine

BCG Control Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who the Investigator believes that they can and will comply with the requirements of the protocol
• Subjects who have no evidence of exposition to BCG as demonstrated by a ELISPOT PPD assay along with no history of BCG vaccination and no BCG scar
• A male or female between, and including, 18 and 45 years of age at the time of the vaccination.
• Written informed consent obtained from the subject prior to any study procedure.
• If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception
• Clinically acceptable laboratory values for blood tests.
• Seronegative for human immunodeficiency virus 1 and -2 (HIV-1/2) antibodies, p24 antigen, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies.
• No evidence of pulmonary pathology as confirmed by chest X-ray.
• No history of extrapulmonary TB.
• No history of previous contact with M. tuberculosis (latent tuberculosis) as demonstrated by a negative ELISPOT Tb (ESAT-6, CFP10) assay.

You may not qualify if:

• History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunisations (any vaccine).
• History of allergic disease or reactions
• History of previous administration of experimental Mycobacterium tuberculosis vaccines.
• Use of any investigational or non-registered product (drug or vaccine) in another experimental protocol other than the study vaccines within 30 days preceding the vaccination, or planned use during the study period.
• Any chronic drug therapy to be continued during the study period.
• Chronic administration of immunosuppressors or other immune-modifying drugs.
• Administration of any immunoglobulins, any immunotherapy and/or any blood products within the three months preceding the vaccination, or planned administrations during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition (including HIV) based on medical history and physical examination.
• Any condition or history of any acute or chronic illness or medication which, in the opinion of the Investigator, may interfere with the evaluation of the study objectives.
• A family history of congenital or hereditary immunodeficiency.
• A stay of more than 2 months in a highly endemic area (e.g. Eastern Europe (Romania, Bulgaria) and low-income countries) within 6 months prior to the screening visit or travel of more than 2 months foreseen in an area of high endemicity after the enrolment into the study.
• History of any neurologic disorders or seizures.
• History of chronic alcohol consumption and/or drug abuse.
• Major congenital defects.
• Pregnant or lactating female.

Sponsors & Collaborators

• Biofabri, S.L: lead
• Universidad de Zaragoza: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator
• TuBerculosis Vaccine Initiative: collaborator

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (6)

• 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

• Verreck FA, Vervenne RA, Kondova I, van Kralingen KW, Remarque EJ, Braskamp G, van der Werff NM, Kersbergen A, Ottenhoff TH, Heidt PJ, Gilbert SC, Gicquel B, Hill AV, Martin C, McShane H, Thomas AW. MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques. PLoS One. 2009;4(4):e5264. doi: 10.1371/journal.pone.0005264. Epub 2009 Apr 15.

  PMID: 19367339 BACKGROUND

• Gonzalo-Asensio J, Mostowy S, Harders-Westerveen J, Huygen K, Hernandez-Pando R, Thole J, Behr M, Gicquel B, Martin C. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS One. 2008;3(10):e3496. doi: 10.1371/journal.pone.0003496. Epub 2008 Oct 23.

  PMID: 18946503 BACKGROUND

• Martin C, Williams A, Hernandez-Pando R, Cardona PJ, Gormley E, Bordat Y, Soto CY, Clark SO, Hatch GJ, Aguilar D, Ausina V, Gicquel B. The live Mycobacterium tuberculosis phoP mutant strain is more attenuated than BCG and confers protective immunity against tuberculosis in mice and guinea pigs. Vaccine. 2006 Apr 24;24(17):3408-19. doi: 10.1016/j.vaccine.2006.03.017.

  PMID: 16564606 BACKGROUND

• Perez E, Samper S, Bordas Y, Guilhot C, Gicquel B, Martin C. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol. 2001 Jul;41(1):179-87. doi: 10.1046/j.1365-2958.2001.02500.x.

  PMID: 11454210 BACKGROUND

• 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 RESULT

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This is a first-in-human Phase 1 trial designed to evaluate the safety and tolerability profile of MTBVAC in comparison to BCG.

Results Point of Contact

• Title: Dr. François Spertini, Associate Professor, Division Immunology & Allergy
• Organization: Centre Hospitalier Universitaire Vaudois (CHUV)

Francois.Spertini@chuv.ch

+41 21 31 40 799

Study Officials

• François Spertini, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: December 3, 2013
• First Posted: December 17, 2013
• Study Start: January 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: November 1, 2014
• Last Updated: March 24, 2017
• Results First Posted: March 24, 2017

Record last verified: 2017-02

Locations

CH (1)