TuberculosisPhase 1/2MTBVAC-Ph1bNCT02729571
Dose-escalation Safety and Immunogenicity Study to Compare MTBVAC to BCG in Newborns With a Safety Arm in Adults
A Phase 1/2 study testing MTBVAC and BCG in people with Tuberculosis, run by Biofabri, S.L at 1 site in South Africa.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 day to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- MTBVAC and BCG
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteSouth Africa
- Study dates
- Sep 2015to Mar 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 1 day to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
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- 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.
- Apgar score at 5 minutes more than or equal to 7.
- A maternal HIV test result (rapid test, ELISA or PCR) taken during pregnancy must be available, documented and negative.
- Estimated gestational age more than or equal to 38 weeks
Who cannot join
- Adult stage Exclusion criteria
- 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 Stage Exclusion criteria:
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- 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.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
South African Tuberculosis Vaccine Initiative, Brewelskloof Hospital
Worcester, Western Cape, 6850
About this study
Official title: A Randomized, Double-blind, Dose-escalation Clinical Trial of the Safety, Reactogenicity and Immunogenicity of MTBVAC Compared to BCG Vaccine SSI, in Newborns Living in a Tuberculosis Endemic Region With a Safety Arm in Adults
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).
Read the detailed description
Adult Stage:
Eighteen (18) adult participants will be recruited and randomized equally into 1 of 2 study groups (n=9 per group): MTBVAC highest dose group (approx. 5x10E05 CFU/0.1mL) or BCG SSI standard human dose (approx. 5x10E05 CFU/0.1mL).
Safety assessments will be conducted at D0, D7, D14, D28, D56, D90, and D180 post study vaccination. A diary card will be used to collect solicited local, regional, and systemic adverse event data from D0 through D14. Reactogenicity data will be collected at each study visit. Non-serious adverse events will be collected through D28. Serious adverse events will be collected during the entire study period.
Infant Stage:
Thirty-six (36) infant participants will be recruited, randomized and allocated into 4 groups of 9 participants: BCG (single dose level 2.5 x 10E05 CFU/0.05 mL); or MTBVAC at three different dose levels (lowest 2.5x10E03 CFU/0.05mL, middle 2.5x10E04 CFU/0.05mL, highest 2.5x10E05 CFU/0.05mL).
Vaccination of neonates will be staggered by cohorts on a 3 verum : 1 control basis to allow gradual evaluation of safety and reactogenicity, as follows:
Cohort 1: 9 who receive the lowest MTBVAC dose level and 3 BCG control; Cohort 2: 9 who receive the highest MTBVAC dose level and 3 BCG control; Cohort 3: 9 who receive the highest MTBVAC dose level and 3 BCG control.
All AEs and biochemical and haematological parameters (safety data) collected up until Day 28 after vaccination of the last subject of each cohort will be reviewed by DSMB to authorize progression to the next group. Safety assessments will be conducted at D0, D7, D14, D28, D70, D90, D180 and D360 post study vaccination. A diary card will be used to collect solicited local, regional, and systemic adverse event data from D0 through D14. Reactogenicity data will be collected at each study visit. Non-serious adverse events will be collected through D28. Serious adverse events will be collected during the entire study period. Unscheduled follow-up face-to-face visits will be performed as needed for safety and adverse event management.
- Conditions
- Tuberculosis
- Being tested
- MTBVAC, BCG
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTBVACBiological
Live-attenuated tuberculosis vaccine
BCGBiological
Commercially available live-attenuated tuberculosis vaccine
| Study group | Role | What they receive |
|---|---|---|
| MTBVAC Group 1 | Experimental | Intervention: MTBVAC live vaccine (low dose) Receives: Biological: MTBVAC |
| MTBVAC Group 2 | Experimental | Intervention: MTBVAC live vaccine (middle dose) Receives: Biological: MTBVAC |
| MTBVAC Group 3 | Experimental | Intervention: MTBVAC live vaccine (high dose) Receives: Biological: MTBVAC |
| BCG Control Group | Active comparator | Intervention: commercially available BCG live vaccine Receives: Biological: BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Six (6) months post-study vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startSep 2015
- Primary completionSep 2016
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biofabri, S.L
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- South African Tuberculosis Vaccine Initiative, TuBerculosis Vaccine Initiative, Triclinium Clinical Trial Project Management (Pty) Ltd., Universidad de Zaragoza
- Responsible party
- Sponsor
- Investigators
- Michele Tameris, MD, Principal investigator, South African Tuberculosis Vaccine Initiative
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02729571
- Sponsor's protocol ID
- MTBVAC-02
- Acronym
- MTBVAC-Ph1b
- Status last verified
- Apr 2018
- First submitted
- 15 Mar 2016
- Last updated
- 1 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 26598141Aguilo 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.
PubMed 26786657Arbues 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 23965219Tameris 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.
PubMed 31416768
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Dose-escalation Clinical Trial of the Safety, Reactogenicity and Immunogenicity of MTBVAC Compared to BCG Vaccine SSI, in Newborns Living in a Tuberculosis Endemic Region With a Safety Arm in Adults
- ClinicalTrials.gov ID
- NCT02729571
- Acronym / sponsor ID
- MTBVAC-Ph1b / MTBVAC-02
- Conditions
- Tuberculosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Biofabri, S.LIndustry (pharma, biotech, devices)
- Collaborators
- South African Tuberculosis Vaccine Initiative, TuBerculosis Vaccine Initiative, Triclinium Clinical Trial Project Management (Pty) Ltd., Universidad de Zaragoza
- Study start
- Sep 2015
- Primary completion
- Sep 2016 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Adult Stage:
Eighteen (18) adult participants will be recruited and randomized equally into 1 of 2 study groups (n=9 per group): MTBVAC highest dose group (approx. 5x10E05 CFU/0.1mL) or BCG SSI standard human dose (approx. 5x10E05 CFU/0.1mL).
Safety assessments will be conducted at D0, D7, D14, D28, D56, D90, and D180 post study vaccination. A diary card will be used to collect solicited local, regional, and systemic adverse event data from D0 through D14. Reactogenicity data will be collected at each study visit. Non-serious adverse events will be collected through D28. Serious adverse events will be collected during the entire study period.
Infant Stage:
Thirty-six (36) infant participants will be recruited, randomized and allocated into 4 groups of 9 participants: BCG (single dose level 2.5 x 10E05 CFU/0.05 mL); or MTBVAC at three different dose levels (lowest 2.5x10E03 CFU/0.05mL, middle 2.5x10E04 CFU/0.05mL, highest 2.5x10E05 CFU/0.05mL).
Vaccination of neonates will be staggered by cohorts on a 3 verum : 1 control basis to allow gradual evaluation of safety and reactogenicity, as follows:
Cohort 1: 9 who receive the lowest MTBVAC dose level and 3 BCG control; Cohort 2: 9 who receive the highest MTBVAC dose level and 3 BCG control; Cohort 3: 9 who receive the highest MTBVAC dose level and 3 BCG control.
All AEs and biochemical and haematological parameters (safety data) collected up until Day 28 after vaccination of the last subject of each cohort will be reviewed by DSMB to authorize progression to the next group. Safety assessments will be conducted at D0, D7, D14, D28, D70, D90, D180 and D360 post study vaccination. A diary card will be used to collect solicited local, regional, and systemic adverse event data from D0 through D14. Reactogenicity data will be collected at each study visit. Non-serious adverse events will be collected through D28. Serious adverse events will be collected during the entire study period. Unscheduled follow-up face-to-face visits will be performed as needed for safety and adverse event management.
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: MTBVACIntervention: MTBVAC live vaccine (low dose) |
| MTBVAC Group 2 | Experimental | Biological: MTBVACIntervention: MTBVAC live vaccine (middle dose) |
| MTBVAC Group 3 | Experimental | Biological: MTBVACIntervention: MTBVAC live vaccine (high dose) |
| BCG Control Group | Active comparator | Biological: BCGIntervention: commercially available BCG live vaccine |
Who may qualify
- Ages
- 1 day to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (10 listed)
- Adult stage Exclusion criteria
- 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
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 |
|---|---|---|
| MTBVACLive-attenuated tuberculosis vaccine | Biological | MTBVAC Group 1, MTBVAC Group 2, MTBVAC Group 3 |
| BCGCommercially available live-attenuated tuberculosis vaccine | Biological | BCG Control Group |
Primary outcome
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.
Time frame: Six (6) months post-study vaccination
1 secondary outcome
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.
Time frame: Six (6) months post-study vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2018.
- Background: 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.
- Background: PubMed 26786657Aguilo 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.
- 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.
- Derived from this study: PubMed 31416768Tameris 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.
- 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.
Michele Tameris, MD principal investigator
South African Tuberculosis Vaccine Initiative
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MTBVAC and BCG in people with Tuberculosis, run by Biofabri, S.L at 1 site in South Africa.
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 18 inclusion and 10 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 1 May 2018. 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 South Africa. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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. (time frame: Six (6) months post-study vaccination). 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 NCT02729571, which also lists 4 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 1 May 2018.