TuberculosisPhase 1MTBVACNCT02013245
Dose-Escalation Study to Evaluate the Safety and Immunogenicity of MTBVAC Vaccine in Comparison With BCG Vaccine.
A Phase 1 study testing MTBVAC live vaccine and Commercially available BCG live vaccine in people with Tuberculosis and Healthy, run by Biofabri, S.L at 1 site in Switzerland.
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). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Healthy
- What is being tested?
- MTBVAC live vaccine and Commercially available BCG live vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2013to Nov 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Centre Hospitalier Universitaire Vaudois
Lausanne, Canton of Vaud, 1011
About this study
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
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.
Read the 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.
- Conditions
- Tuberculosis, Healthy
- Being tested
- MTBVAC live vaccine, Commercially available BCG live vaccine
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTBVAC live vaccineBiological
Live-attenuated Mycobacterium tuberculosis vaccine
Commercially available BCG live vaccineBiological
Live-attenuated Mycobacterium bovis vaccine
| Study group | Role | What they receive |
|---|---|---|
| MTBVAC group 1 | Experimental | Intervention: MTBVAC live vaccine (low dose 5 x 10E03 CFU/0.1mL) Receives: Biological: MTBVAC live vaccine |
| MTBVAC Group 2 | Experimental | Intervention: MTBVAC live vaccine (middle dose 5 x 10E04 CFU/0.1mL) Receives: Biological: MTBVAC live vaccine |
| MTBVAC Group 3 | Experimental | Intervention: MTBVAC live vaccine (high dose 5 x 10E05 CFU/0.1mL) Receives: Biological: MTBVAC live vaccine |
| BCG Control Group | Active comparator | Intervention: Commercially available BCG live vaccine (dose 5 x 10E05 CFU/0.1mL) Receives: Biological: Commercially available BCG live vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 7 months follow up
Secondary outcomes (1)
Number of Participants With Three-cytokine-positive CD4+ T-cell Response
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
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2013 (estimated)
- Study startJan 2013
- Primary completionJun 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biofabri, S.L
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Universidad de Zaragoza, Centre Hospitalier Universitaire Vaudois, TuBerculosis Vaccine Initiative
- Responsible party
- Sponsor
- Investigators
- François Spertini, MD, Principal investigator, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02013245
- Sponsor's protocol ID
- MTBVAC-01
- Acronym
- MTBVAC
- Status last verified
- Feb 2017
- First submitted
- 3 Dec 2013
- Last updated
- 24 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 23965219Verreck 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.
PubMed 19367339Gonzalo-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.
PubMed 18946503Martin 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.
PubMed 16564606Perez 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.
PubMed 11454210Spertini 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.
PubMed 26598141
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02013245
- Acronym / sponsor ID
- MTBVAC / MTBVAC-01
- Conditions
- Tuberculosis, Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Biofabri, S.LIndustry (pharma, biotech, devices)
- Collaborators
- Universidad de Zaragoza, Centre Hospitalier Universitaire Vaudois, TuBerculosis Vaccine Initiative
- Study start
- Jan 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 17 Dec 2013 (estimated)
- Results
- Posted 24 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MTBVAC group 1 | Experimental | Biological: MTBVAC live vaccineIntervention: MTBVAC live vaccine (low dose 5 x 10E03 CFU/0.1mL) |
| MTBVAC Group 2 | Experimental | Biological: MTBVAC live vaccineIntervention: MTBVAC live vaccine (middle dose 5 x 10E04 CFU/0.1mL) |
| MTBVAC Group 3 | Experimental | Biological: MTBVAC live vaccineIntervention: MTBVAC live vaccine (high dose 5 x 10E05 CFU/0.1mL) |
| BCG Control Group | Active comparator | Biological: Commercially available BCG live vaccineIntervention: Commercially available BCG live vaccine (dose 5 x 10E05 CFU/0.1mL) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MTBVAC live vaccineLive-attenuated Mycobacterium tuberculosis vaccine | Biological | MTBVAC Group 2, MTBVAC Group 3, MTBVAC group 1 |
| Commercially available BCG live vaccineLive-attenuated Mycobacterium bovis vaccine | Biological | BCG Control Group |
Primary outcome
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
1 secondary outcome
Number of Participants With Three-cytokine-positive CD4+ T-cell Response
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23965219Arbues 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.
- Background: PubMed 19367339Verreck 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.
- Background: PubMed 18946503Gonzalo-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.
- Background: PubMed 16564606Martin 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.
- Background: PubMed 11454210Perez 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.
- Results publication: PubMed 26598141Spertini 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
François Spertini, MD principal investigator
Centre Hospitalier Universitaire Vaudois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MTBVAC live vaccine and Commercially available BCG live vaccine in people with Tuberculosis and Healthy, run by Biofabri, S.L at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events up to 210 Days After Vaccination (time frame: 7 months follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02013245, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2017.