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

February 6, 2017 updated by: Biofabri, S.L

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A randomized, double-blind, controlled Phase I study conducted at CHUV, Lausanne, Switzerland, to compare MTBVAC to licensed BCG in healthy, PPD-negative adult male and female volunteers. The study involves random allocation of up to 36 subjects (4 vaccine groups of 9 volunteers fulfilling the inclusion criteria) to MTBVAC (tested at three separate doses) or standard dose BCG (on a 3 verum : 1control basis) in a dose-escalation manner to one of three cohorts. Each cohort includes 9 subjects set to receive MTBVAC lowest dose 5x10E03, or MTBVAC intermediate dose 5x10E04, or high dose 5x10E05 colony forming units (CFU) in 0.1 mL and 3 subjects set to receive standard dose BCG (5x10E05 CFU in 0.1 mL). A single intradermal injection is given in the non-dominant arm of each volunteer starting with the lowest MTBVAC dose. Each MTBVAC vaccine dose is administered staggered by cohort, starting with the cohort with the lowest MTBVAC dose level. After at least 35 days of follow-up within each cohort a safety review and evaluation by Independent Data Safety Monitoring Board provides go/no-go for vaccination of the subsequent cohorts if no safety issues as defined by preset stopping rules.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Switzerland, 1011
        • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MTBVAC group 1
Intervention: MTBVAC live vaccine (low dose 5 x 10E03 CFU/0.1mL)
Biological: MTBVAC live vaccine
Live-attenuated Mycobacterium tuberculosis vaccine
Experimental: MTBVAC Group 2
Intervention: MTBVAC live vaccine (middle dose 5 x 10E04 CFU/0.1mL)
Biological: MTBVAC live vaccine
Live-attenuated Mycobacterium tuberculosis vaccine
Experimental: MTBVAC Group 3
Intervention: MTBVAC live vaccine (high dose 5 x 10E05 CFU/0.1mL)
Biological: MTBVAC live vaccine
Live-attenuated Mycobacterium tuberculosis vaccine
Active Comparator: BCG Control Group
Intervention: Commercially available BCG live vaccine (dose 5 x 10E05 CFU/0.1mL)
Biological: Commercially available BCG live vaccine
Live-attenuated Mycobacterium bovis vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events up to 210 Days After Vaccination
Time Frame: 7 months follow up

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Three-cytokine-positive CD4+ T-cell Response
Time Frame: Day 28
Measure of the kinetics of CD4+ T-cell responses to MTBVAC or BCG vaccination by tracking the expression of IFNγ, TNFα and IL-2 upon stimulation with live MTBVAC or BCG
Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biofabri, S.L

Collaborators

Centre Hospitalier Universitaire Vaudois
TuBerculosis Vaccine Initiative
Universidad de Zaragoza

Investigators

  • Principal Investigator: Francois Spertini, MD, Centre Hospitalier Universitaire Vaudois

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

December 3, 2013

First Submitted That Met QC Criteria

December 11, 2013

First Posted (Estimate)

December 17, 2013

Study Record Updates

Last Update Posted (Actual)

March 24, 2017

Last Update Submitted That Met QC Criteria

February 6, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MTBVAC-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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