Phase 2 Study of PA-824 for Treatment of Pulmonary Tuberculosis

Information

  • Research Project
  • 10496816
  • ApplicationId
    10496816
  • Core Project Number
    R01FD004794
  • Full Project Number
    3R01FD004794-04S1
  • Serial Number
    004794
  • FOA Number
    RFA-FD-13-001
  • Sub Project Id
  • Project Start Date
    8/15/2014 - 9 years ago
  • Project End Date
    7/31/2022 - a year ago
  • Program Officer Name
    MUELLER, CHRISTINE
  • Budget Start Date
    8/1/2018 - 5 years ago
  • Budget End Date
    7/31/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    04
  • Suffix
    S1
  • Award Notice Date
    9/29/2021 - 2 years ago
Organizations

Phase 2 Study of PA-824 for Treatment of Pulmonary Tuberculosis

DESCRIPTION (provided by applicant): Tuberculosis (TB) is a leading cause of infectious disease death, especially in HIV-prevalent regions, and the emergence of highly resistant TB further threatens global TB control. There is a need for highly potent TB treatments that can cure disease in substantially fewer than the six months currently required. PA-824, an investigational nitroimidazole with bactericidal and sterilizing activity against Mycobacterium tuberculosis (M. tuberculosis), has potential as a treatment-shortening drug when used as part of multidrug TB therapy. In an experimental murine model of TB, PA-824 was shown to have bactericidal activity during the early phase of TB treatment and sterilizing activity during the continuation phase of TB therapy when given as monotherapy. In subsequent murine studies, using PA-824 in combination with a multidrug regimen containing rifampin and pyrazinamide reduced the treatment time required for cure from six months to four months. The applicant reported that Phase 1 and early Phase 2 studies suggest that PA-824 is well tolerated and has measurable, dose-dependent early bactericidal activity, reducing sputum colony counts of M. tuberculosis over two weeks of once-daily dosing. The main objective of the proposed Phase 2 clinical trial is to evaluate the antimicrobial activity of PA-824 when added to standard-dose TB treatment over the first 12 weeks of TB treatment. Patients with sputum smear-positive pulmonary TB in Cape Town, South Africa, will receive standard doses of isoniazid, rifampin, and pyrazinamide and will be randomized to receive PA-824 200 mg once daily for 8 weeks (Arm 1), PA-824 200 mg once daily for 12 weeks (Arm 2), or ethambutol at standard doses for 8 weeks (control arm). The primary efficacy endpoint will be time to stable sputum culture conversion in liquid media, defined as the time from the start of treatment until the first of at least two negative sputum cultures, over 12 weeks. The primary safety endpoint is grade 3 or higher adverse events. Pharmacokinetics, solid culture results after 8 weeks of treatment, change in time to sputum culture positivity in liquid culture, and quantitative change in extent of disease on computed tomography will also be assessed. Results will determine the antimicrobial activity of daily PA-824 and inform further development of PA-824.

IC Name
FOOD AND DRUG ADMINISTRATION
  • Activity
    R01
  • Administering IC
    FD
  • Application Type
    3
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    100000
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    103
  • Ed Inst. Type
    SCHOOLS OF MEDICINE
  • Funding ICs
    FDA:100000\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZFD1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    JOHNS HOPKINS UNIVERSITY
  • Organization Department
    INTERNAL MEDICINE/MEDICINE
  • Organization DUNS
    001910777
  • Organization City
    BALTIMORE
  • Organization State
    MD
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    212182680
  • Organization District
    UNITED STATES