DAR-901 TB Booster Vaccine to Prevent TB in Adolescents (DAR-PIA)

• ClinicalTrials.gov Identifier: NCT02712424
• Recruitment Status: Completed
• First Posted: March 18, 2016
• Results First Posted: May 11, 2021
• Last Update Posted: May 11, 2021
• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborator: Muhimbili University of Health and Allied Sciences
• Information provided by (Responsible Party): C. Fordham von Reyn, Dartmouth-Hitchcock Medical Center

Tracking Information

• First Submitted Date: March 14, 2016
• First Posted Date: March 18, 2016
• Results First Submitted Date: February 10, 2021
• Results First Posted Date: May 11, 2021
• Last Update Posted Date: May 11, 2021
• Study Start Date: March 2016
• Actual Primary Completion Date: February 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2021)

New Infection With Mycobacterium Tuberculosis [ Time Frame: 3 years ]

New infection with TB is based on conversion of IGRA

Original Primary Outcome Measures (submitted: March 14, 2016)

New infection with Mycobacterium tuberculosis [ Time Frame: 2 years ]

Based on conversion of IGRA

Current Secondary Outcome Measures (submitted: April 17, 2021)

Persistent New Infection With M. Tuberculosis [ Time Frame: 3 years ]

New positive IGRA that is also positive on repeat ≥3 mos later

Original Secondary Outcome Measures (submitted: March 14, 2016)

Persistent new infection with M. tuberculosis [ Time Frame: 2 years ]

New positive IGRA that is also positive on repeat ≥3 mos later

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Tuberculosis

Intervention

• Biological: DAR-901
• Biological: Sterile saline placebo

Study Arms

• Active Comparator: DAR-901
  0.1 mL intradermal injection of 1 mg DAR-901
  Intervention: Biological: DAR-901
• Placebo Comparator: Placebo
  0.1 mL intradermal injection of sterile saline for human use
  Intervention: Biological: Sterile saline placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 17, 2021): 625
• Original Estimated Enrollment (submitted: March 14, 2016): 650
• Actual Study Completion Date: February 1, 2020
• Actual Primary Completion Date: February 1, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria: Negative IGRA at baseline -

Exclusion Criteria: Pregnancy, serious underlying disease

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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Years to 15 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Tanzania

Administrative Information

• NCT Number: NCT02712424
• Other Study ID Numbers: 29001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: C. Fordham von Reyn, Dartmouth-Hitchcock Medical Center
• Original Responsible Party: Dartmouth-Hitchcock Medical Center
• Current Study Sponsor: Dartmouth-Hitchcock Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Muhimbili University of Health and Allied Sciences

Investigators

• Principal Investigator: C Fordham von Reyn, MD; Dartmouth-Hitchcock Medical Center

• PRS Account: Dartmouth-Hitchcock Medical Center
• Verification Date: April 2021