Tuberculosis
Conditions
Keywords
Vaccine
Brief summary
DAR-901 booster vaccine or placebo will be administered to adolescents in Tanzania primed with BCG to determine if immunization reduces the risk of TB infection
Detailed description
DAR-901 whole cell booster vaccine to prevent TB infection in adolescents (DAR-PIA) This is a Phase II, 3-injection, randomized, controlled trial of DAR-901 to be conducted in 13-15 year old adolescents in Tanzania previously immunized with BCG. DAR-901 is a whole cell inactivated non-tuberculous mycobacterial vaccine manufactured from the Master Cell Bank of SRL-172 that was used in the successful Phase III DarDar Trial in Tanzania. The goals are to establish the safety and efficacy of DAR-901 in preventing infection with TB. The 1 mg dose was selected during the current Phase I dose-escalation trial of DAR-901 in the US being conducted by Dartmouth and Aeras. The 1 mg dose corresponds to the dose of SRL 172 used in the DarDar Trial. All subjects will be screened by the T-spot® IGRA (Oxford Immunotec, Oxford, England) for evidence of TB infection. All screened subjects will have a structured interview to identify risk factors for TB infection (=positive IGRA). IGRA-positive subjects will be referred for further evaluation and will not be entered in the immunization phase of the trial. It is estimated that 1000 adolescents will need to be screened to identify a total of 650 IGRA-negative adolescents in the immunization phase of the trial. Subjects will be and randomized 1:1 to DAR-901 or saline control at 0, 2 and 4 months. Doses will be administered by intradermal (ID) injection in the deltoid area. IGRA testing will be repeated before dose 2, at 14 months, and again at 24 months. This three year study began in the first quarter of 2016 in Dar es Salaam, is funded by GHIT-Japan and will be directed by Geisel School of Medicine at Dartmouth (PI, F. von Reyn) with collaborators at Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania and Tokyo Medical and Dental University in Japan.
Interventions
BIOLOGICALDAR-901
BIOLOGICALSterile saline placebo
Sponsors
Muhimbili University of Health and Allied Sciences
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
Negative IGRA at baseline -
Exclusion criteria
Pregnancy, serious underlying disease \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| New Infection With Mycobacterium Tuberculosis | 3 years | New infection with TB is based on conversion of IGRA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistent New Infection With M. Tuberculosis | 3 years | New positive IGRA that is also positive on repeat ≥3 mos later |
Countries
Tanzania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DAR-901 0.1 mL intradermal injection of 1 mg DAR-901
DAR-901 | 315 |
| Placebo 0.1 mL intradermal injection of sterile saline for human use
Sterile saline placebo | 310 |
| Total | 625 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 34 | 32 |
Baseline characteristics
| Characteristic | DAR-901 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 315 Participants | 310 Participants | 625 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 14.1 years STANDARD_DEVIATION 0.76 | 14.2 years STANDARD_DEVIATION 0.75 | 14.15 years STANDARD_DEVIATION 0.755 |
| IGRA negative | 315 Participants | 310 Participants | 625 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 315 Participants | 310 Participants | 625 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Tanzania | 315 participants | 310 participants | 625 participants |
| Sex: Female, Male Female | 192 Participants | 169 Participants | 361 Participants |
| Sex: Female, Male Male | 123 Participants | 141 Participants | 264 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 315 | 0 / 310 |
| other Total, other adverse events | 126 / 315 | 142 / 310 |
| serious Total, serious adverse events | 6 / 315 | 3 / 310 |
Outcome results
Primary
New Infection With Mycobacterium Tuberculosis
New infection with TB is based on conversion of IGRA
Time frame: 3 years
Population: Conversion from IGRA neg to pos
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DAR-901 | New Infection With Mycobacterium Tuberculosis | 19 Participants |
| Placebo | New Infection With Mycobacterium Tuberculosis | 18 Participants |
Secondary
Persistent New Infection With M. Tuberculosis
New positive IGRA that is also positive on repeat ≥3 mos later
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DAR-901 | Persistent New Infection With M. Tuberculosis | 10 participants |
| Placebo | Persistent New Infection With M. Tuberculosis | 5 participants |