Clinical trial NCT02712424: DAR-901 TB Booster Vaccine to Prevent TB in Adolescents
Official title: A Phase 2, Randomized, Placebo-Controlled, Double-Blind, Study of the Prevention of Infection With Mycobacterium Tuberculosis Among Adolescents Who Have Previously Received BCG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Vaccine
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: Muhimbili University of Health and Allied Sciences
First posted: 2016-03-18
Enrollment: 625
Sex: ALL
Minimum age (years): 13
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria: Negative IGRA at baseline -

Exclusion Criteria: Pregnancy, serious underlying disease

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Primary outcomes:
measure: New Infection With Mycobacterium Tuberculosis
timeFrame: 3 years
Secondary outcomes:
measure: Persistent New Infection With M. Tuberculosis
timeFrame: 3 years
Other outcomes:
Locations:
city: Dar es Salaam
country: Tanzania
facility: Muhimbili University of Health and Allied Sciences
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: C Fordham von Reyn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Munseri P, Said J, Amour M, Magohe A, Matee M, Rees CA, Mackenzie T, Tvaroha S, Bailey-Kellogg C, Maro I, Wieland-Alter W, Adams LV, Horsburgh CR, Nakamura K, Arbeit RD, Pallangyo K, von Reyn CF. DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial. Vaccine. 2020 Oct 27;38(46):7239-7245. doi: 10.1016/j.vaccine.2020.09.055. Epub 2020 Sep 29.
citation: Rees CA, Pineros DB, Amour M, Munseri P, Said J, Magohe A, Matee M, Pallangyo K, von Reyn CF. The potential of CBC-derived ratios (monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte) to predict or diagnose incident TB infection in Tanzanian adolescents. BMC Infect Dis. 2020 Aug 18;20(1):609. doi: 10.1186/s12879-020-05331-w.