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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Tuberculosis
- Sponsor
- Biofabri, S.L
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief 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). 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult stage:
- •Inclusion criteria:
- •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
- •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
Exclusion Criteria
- •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:
- •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.
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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.(Six (6) months post-study vaccination)