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

Healthy Clinical Trial

— MTBVAC  

Official title:

Phase I Double Blind, Randomized, Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of MTBVAC in Comparison With BCG in Elispot TB(ESAT-6, CFP10, PPD)- and HIV- Negative Volunteers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02013245
• Other study ID #: MTBVAC-01
• Status: Active, not recruiting
• Phase: N/A
• First received: December 3, 2013
• Last updated: December 11, 2013
• Start date: January 2013

Study information

• Verified date: December 2013
• Source: Biofabri, S.L
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Healthy
• Tuberculosis

Intervention

Biological:
• Biological MTBVAC and biological BCG (commercial)

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Canton of Vaud

Sponsors (5)

Lead Sponsor	Collaborator
Biofabri, S.L	Centre Hospitalier Universitaire Vaudois, European Union, Tuberculosis Vaccine Initiative (TBVI), Universidad de Zaragoza

Country where clinical trial is conducted

Switzerland, 

References & Publications (5)

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. — View Citation

Gonzalo-Asensio J, Mostowy S, Harders-Westerveen J, Huygen K, Hernández-Pando R, Thole J, Behr M, Gicquel B, Martín 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. — View Citation

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. — View Citation

Pérez E, Samper S, Bordas Y, Guilhot C, Gicquel B, Martín C. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol. 2001 Jul;41(1):179-87. — View Citation

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. Erratum in: PLoS One. 2011;6(2). doi:10.1371/annotation/e599dafd-8208-4655-a792-21cb125f7f66. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and reactogenicity for all subjects.	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	Yes
Secondary	Cell mediated immune response assessment		7 months follow up	No