drugset / Trial / NCT03561753
Pilot Clinical Trial of PRS TB Regimen I - Phase II
Phase 4
Completed
97 enrolled
Shanghai Pulmonary Hospital, Shanghai, China
Bill and Melinda Gates Foundation · collabNo.85 Hospital, Changning, Shanghai, China · collabShanghai Center for Disease Control and Prevention · collabShanghai Public Health Clinical Center · collabUniversity of California, Los Angeles · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
Tuberculosis is the current leading cause of death due to an identifiable infectious agent worldwide. The current standard regimen for tuberculosis requires a patient to take drug combination (isoniazid, rifampicin, ethambutol, and pyrazinamide) for six to eight month periods. The purpose of this study is to compare tuberculosis treatment therapy between the current standard regimen and PRS derived combinatorial regimen. PRS derived regimen may potentially allow for a shorter course of treatment, which may reduce problems associated with adherence, toxicity, and development of drug resistance.
Timeline
- Start
- 2017-12-01
- Primary completion
- 2019-12-31
- Completion
- 2020-01-31
Publications
- Background Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov. 2013 May;12(5):388-404. doi: 10.1038/nrd4001.
- Background Zumla A, Chakaya J, Centis R, D'Ambrosio L, Mwaba P, Bates M, Kapata N, Nyirenda T, Chanda D, Mfinanga S, Hoelscher M, Maeurer M, Migliori GB. Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 2015 Mar;3(3):220-34. doi: 10.1016/S2213-2600(15)00063-6. Epub 2015 Mar 9.
- Background Nuermberger EL, Spigelman MK, Yew WW. Current development and future prospects in chemotherapy of tuberculosis. Respirology. 2010 Jul;15(5):764-78. doi: 10.1111/j.1440-1843.2010.01775.x. Epub 2010 Jun 4.
- Background Ma Z, Lienhardt C, McIlleron H, Nunn AJ, Wang X. Global tuberculosis drug development pipeline: the need and the reality. Lancet. 2010 Jun 12;375(9731):2100-9. doi: 10.1016/S0140-6736(10)60359-9. Epub 2010 May 18.
- Background Silva A, Lee BY, Clemens DL, Kee T, Ding X, Ho CM, Horwitz MA. Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2172-9. doi: 10.1073/pnas.1600812113. Epub 2016 Mar 28.
- Background Lee BY, Clemens DL, Silva A, Dillon BJ, Maslesa-Galic S, Nava S, Ding X, Ho CM, Horwitz MA. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time. Nat Commun. 2017 Jan 24;8:14183. doi: 10.1038/ncomms14183.
- Background Handbook of anti-tuberculosis agents. Introduction. Tuberculosis (Edinb). 2008 Mar;88(2):85-6. doi: 10.1016/S1472-9792(08)70002-7. No abstract available.
- Background Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, Bernardo J, Venkataramanan R, Sterling TR; ATS (American Thoracic Society) Hepatotoxicity of Antituberculosis Therapy Subcommittee. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006 Oct 15;174(8):935-52. doi: 10.1164/rccm.200510-1666ST.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Clofazimine | Small molecule | 0.15 g | Oral |
| Comparator | Ethambutol | Small molecule | 0.75 g | Oral |
| Comparator | Ethambutol | Small molecule | 1 g | Oral |
| Comparator | Isoniazid | Small molecule | 0.3 g | Oral |
| Subject | Protionamide | Small molecule | 0.6 g | Oral |
| Comparator | Pyrazinamide | Small molecule | 1.5 g | Oral |
| Comparator | Pyrazinamide | Small molecule | 1.75 g | Oral |
| Comparator | Pyrazinamide | Small molecule | 2 g | Oral |
| Comparator | Rifampin | Small molecule | 0.45 g | Oral |
| Comparator | Rifampin | Small molecule | 0.6 g | Oral |