Pilot Clinical Trial of PRS TB Regimen I - Phase II

• Status: Completed
• Trial end date: 2020-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Collaborators: Bill and Melinda Gates Foundation; Eighty-fifth Hospital of the PLA,Shanghai,China.; No.85 Hospital, Changning, Shanghai, China; Shanghai Center for Disease Control and Prevention; Shanghai Public Health Clinical Center; University of California, Los Angeles
• Treatments: Ethambutol; Isoniazid; Pyrazinamide; Rifampin

Criteria

Inclusion Criteria:

1. Newly diagnosed and untreated sputum smear positive tuberculosis patient

2. Pulmonary lesion consistent with TB by radiological examination

3. Positive sputum culture, identification of bacterial type confirmed Mycobacterium tuberculosis. MGIT drug sensitivity test (DST) results are sensitive of the first-line drugs (isoniazid, streptomycin, rifampicin and ethambutol).

4. Age 18 years-65 years old

5. Males or non-pregnant, non-nursing females

6. Women of child-bearing potential who are not surgically sterilized must agree to practice a barrier method of contraception or abstain from heterosexual intercourse during study drug treatment.

a.Effective birth control methods: i.A double contraceptive method should be used as follows: ii.Double barrier method which can include any 2 of the following: a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together); or iii.Barrier method (one of the above) combined with hormone-based contraceptives or an intra-uterine device for the female subject/partner; iv.and are willing to continue practicing birth control methods throughout treatment and for 6 months (both male and female subjects) after the last dose of study medication or discontinuation from study medication in case of premature discontinuation.

7. Laboratory parameters done at or within 14 days prior to screening:

1. Serum or plasma aminotransferases (AST, ALT) less than 3 times the upper limit of normal

2. Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal

3. Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal

4. Serum or plasma potassium level greater than or equal to 3.5 meq/L

5. Hemoglobin level of 7.0 g/dL or greater

6. Platelet count of 100,000/mm3 or greater

7. For women of childbearing potential, a negative pregnancy test is required during screening

8. Provides written informed consent

9. Willingness and ability to attend scheduled follow-up visits and undergo study assessments.

Exclusion Criteria:

1. Tuberculosis resistant to any of the study drugs (isoniazid, rifampin, EMB, PZA, CFZ, Pto)

2. Unable to take oral medications.

3. History of allergy or intolerance to any of the study drugs

4. Serum aminotransferase (AST or ALT) 3x upper limit of normal or higher

5. Pregnant or nursing females, or plan to become pregnant or nurse during the study period

6. Males planning to conceive a child during the study or within 6 months of cessation of treatment.

7. Any treatment directed against active tuberculosis within 6 months preceding initiation of study drugs.

8. Suspected or documented tuberculosis involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis.

9. HIV infected

10. HBV infected or HCV infected (these increase the risk of TB-drug induced hepatotoxicity)

11. Weight less than 40.0 kg.

12. Known allergy or intolerance to any of the study medications.

13. Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any of the study drugs.

14. QTcF > 500 msec

15. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.

16. Current or planned incarceration or other involuntary detention

17. Having participated in other clinical studies with dosing of investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational study that includes treatment with medicinal agents. Subjects who are participating in observational studies or who are in a follow up period of a trial that included drug therapy may be considered for inclusion.