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July 21, 2014 20 th International AIDS Conference

Eight Week Randomized Trial of Treatment with Pa-824 , Moxifloxacin, and Pyrazinamide in Drug Sensitive and Multi-Drug Resistant Tuberculosis. July 21, 2014 20 th International AIDS Conference. Daniel Everitt, MD For the NC-002 Collaborators.

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July 21, 2014 20 th International AIDS Conference

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  1. Eight Week Randomized Trial of Treatment with Pa-824, Moxifloxacin, and Pyrazinamide in Drug Sensitive and Multi-Drug Resistant Tuberculosis 2014 International AIDS Conference July 21, 2014 20th International AIDS Conference Daniel Everitt, MD For the NC-002 Collaborators

  2. NC-002 Pa-M-Z Trial: First Novel Combination StudyIn patients with TB sensitive to Pa, M, and Z Pa(200mg)-M-Z N=60 Pa(100mg)-M-Z N=60 DS H-R-Z-E N=60 2 months of treatment Pa(200mg)-M-Z N= up to 50 Randomize DR Serial 16 hour pooled sputum samples for CFU Count Pa = PA-824 M = moxifloxacin 400 mg Z = pyrazinamide at 1500mg 2014 International AIDS Conference Participants with newly diagnosed smear positive DS and MDR Pulmonary TB

  3. Investigational Sites and Laboratories 2014 International AIDS Conference

  4. Enrolment Demographic Characteristics 2014 International AIDS Conference

  5. Estimates of Mean Serial Log(CFU) Count Over Time Joint Bayesian NLME Regression 2014 International AIDS Conference

  6. Daily Log CFU Reduction – 1o Endpoint *p < 0.05 vs H-R-Z-E No differences from above when adjusted for site, HIV status or baseline CFU as baseline covariates 2014 International AIDS Conference

  7. Estimates of Mean Serial log(TTP) Over TimeJoint Bayesian NLME Regression

  8. Time to Culture Conversion – 2o Endpoint Culture Conversion is the Time when Culture is First Negative *Statistically significant differences compared to HRZE for both solid and liquid culture 2014 International AIDS Conference

  9. Eight Week Culture Conversion – 2o Endpoint *Statistically significant difference from HRZE for liquid culture only 2014 International AIDS Conference

  10. Log CFU Daily Decreases and Pearson Correlation Coefficients Data from Participants Enrolled in the EBA Substudy 2014 International AIDS Conference

  11. Summary of Safety Findings Grade 1 to 4 Treatment-Emergent Adverse Events * % = Percentage of patients with at least one AE in each category

  12. NC-002 Summary of Key Results and Next Steps 2014 International AIDS Conference • Pa-M-Z Regimen was statistically significantly better than the H-R-Z-E control for the primary and 3/5 key secondary endpoints • Greater reduction in colony counts over 56 days • More rapid time to culture conversion • Higher conversion to negative at 8 weeks – Nearly twice the number converted in liquid culture • No significant difference in response for HIV infected patients • Similar effects for patients with MDR-TB, albeit with small numbers • Safety comparable to control • Next Step: The STAND Phase 3 Trial

  13. The STAND Trial - Phase 3 Trial of Pa-M-Z“Shortening Treatment by Advancing Novel Drugs” Pa(100mg)-M-Z N=300 4months of treatment Pa(200mg)-M-Z N=300 12 & 24 mos f/u after randomization DS H-R-Z-E N=300 Pa(200mg)-M-Z N= up to 300 6months of treatment Randomize DR Z = pyrazinamide at 1500mg Pa = PA-824 M = moxifloxacin 400 mg 2014 International AIDS Conference Participants with newly diagnosed smear positive DS- and MDR-TB Pa(200mg)-M-Z N= 300

  14. Sincere Acknowledgments: 2014 International AIDS Conference • Robert Schall • University of the Free State, and Quintiles Biostatistics, Bloemfontein, SA • Christo Van Niekerk • TB Alliance, Pretoria, SA • Almari Conradie • TB Alliance, Pretoria, SA • Carl Mendel • TB Alliance, New York, USA • Rodney Dawson • University of Cape Town Lung Institute, Cape Town, SA • Andreas Diacon • Stellenbosch University, Tygerberg, and TASK Applied Science, Bellville SA • Divan Burger • University of the Free State, and Quintiles Biostatistics, Bloemfontein, SA To the Patients with Tuberculosis who Participated, volunteer Community Advisory Boards, and Lead Investigators and Colleagues:

  15. TB Alliance Supporters Australian AID United States Agency for International Development Bill & Melinda Gates Foundation UNITAID United States Food and Drug Administration National Institute of Allergy and Infectious Diseases AIDS Clinical Trial Group European Commission Irish Aid Global Health Innovative Technology Fund UK aid 2014 International AIDS Conference Thanks to all those who support our mission for better, fast TB drugs

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