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

A Phase 2, Randomized, Placebo-Controlled, Double-Blind, Study of the Prevention of Infection With Mycobacterium Tuberculosis Among Adolescents Who Have Previously Received BCG

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

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: DAR-901; Biological: Sterile saline placebo

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
• Enrollment (Actual): 625
• Phase: Phase 2

Contacts and Locations

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania
    • Muhimbili University of Health and Allied Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Negative IGRA at baseline -

Exclusion Criteria: Pregnancy, serious underlying disease

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DAR-901; 0.1 mL intradermal injection of 1 mg DAR-901	Biological: DAR-901
Placebo Comparator: Placebo; 0.1 mL intradermal injection of sterile saline for human use	Biological: Sterile saline placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New Infection With Mycobacterium Tuberculosis	New infection with TB is based on conversion of IGRA	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent New Infection With M. Tuberculosis	New positive IGRA that is also positive on repeat ≥3 mos later	3 years

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Muhimbili University of Health and Allied Sciences
• Investigators: Principal Investigator: C Fordham von Reyn, MD, Dartmouth-Hitchcock Medical Center

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: April 17, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: 29001