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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03338621
Other study ID # SimpliciTB (B-Pa-M-Z) NC-008
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date July 30, 2018
Est. completion date June 10, 2022

Study information

Verified date March 2024
Source Global Alliance for TB Drug Development
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To evaluate the efficacy, safety and tolerability at 8 weeks (2-months), 52 weeks (12-months), and 104 Weeks (24-months) post the start of the following treatment regimens in participants with: Drug Sensitive TB (DS-TB) patients given BPaMZ for 17 Weeks ( or 4 months) vs. Standard HRZE/HR treatment given for 26 weeks (or 6 months) and Drug Resistant TB (DR-TB) patients given BPaMZ for 26 Weeks (or 6 months)


Description:

Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants. All participants in the below arms will have follow-up for a period of 104 weeks (24 months) from the start of therapy. Participants with Drug Sensitive TB (DS-TB): Participants with DS-TB will be randomized to one of two treatment arms. These participants will receive either BPaMZ daily for 17 weeks (4 months), or HRZE/HR combination tablets daily for 26 weeks (6 months). participants will be stratified for co-infection with human immunodeficiency virus (HIV) and cavitation. Participants with Drug Resistant TB (DR-TB): Participants with DR-TB will be assigned to receive BPaMZ daily for 26 weeks (6 months).


Recruitment information / eligibility

Status Completed
Enrollment 455
Est. completion date June 10, 2022
Est. primary completion date July 1, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease [IUATLD]/WHO scale (Appendix 1) on smear microscopy) at the trial laboratory. - Participants with one of the following pulmonary TB conditions: DS-TB treatment arm participants should be: - sensitive to rifampicin and isoniazid by rapid sputum based test AND - either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB. DR-TB treatment arm participants should be Resistant to rifampicin and/or isoniazid. - Of non-childbearing potential or willing to practice effective methods of birth control - Body weight (in light clothing and no shoes) = 30 kg. - Completed informed consent form Exclusion Criteria: - Karnofsky score <60% - Any risk factor for QT prolongation - Any planned contraindicated medicines - Resistant to fluoroquinolones (rapid, sputum-based molecular screening tests). Any of the following lab toxicities/abnormalities: - CD4+ count < 100 cells/µL (HIV infected participants) - platelets <75,000/mm³ - creatinine >1.5 times upper limit of normal (ULN) - eGFR = 60 mL/min - haemoglobin <8.0 g/dL - serum potassium less than the lower limit of normal for the laboratory. - GGT: greater than 3 x ULN - AST: =3.0 x ULN to be excluded; - ALT: =3.0 x ULN to be excluded - ALP: =3.0 x ULN to be excluded - Total bilirubin: >1.5 x ULN to be excluded; - Direct bilirubin: greater than 1x ULN to be excluded

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Pretomanid
200 mg tablets
Bedaquiline
100 mg tablets
Moxifloxacin
400 mg tablets
Pyrazinamide
500 mg tablets
HRZE
isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets
HR
isoniazid 75 mg plus rifampicin 150 mg combination tablets

Locations

Country Name City State
Brazil Evandro Chagas Rio de Janeiro
Brazil FIOCRUZ Rio de Janeiro
Georgia National Center for Tuberculosis and Lung Diseases Tbilisi
Malaysia Institut Perubatan Respiratori Kuala Lumpur
Philippines Lung Center of Philippines Manila
Philippines Tropical Disease Foundation Manila
Russian Federation Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow
Russian Federation Moscow City Research and Practice Tuberculosis Treatment Centre Moscow
Russian Federation Research Institute of Phthisiopulmonology of I. M. Sechenov First Moscow State Medical University Moscow
Russian Federation Research Institute of the Phthisiopulmonology Sankt Petersburg
Russian Federation Ural Research Institute of Phthisiopulmonology Yekaterinburg
South Africa Madibeng Centre for Research Brits
South Africa TASK Cape Town
South Africa University of Cape Town Lung Institute Cape Town
South Africa CHRU, King Dinuzulu Durban
South Africa Enhancing Care Foundation Durban
South Africa CHRU, Helen Joseph Hospital Johannesburg
South Africa PHRU, Tshepong Hospital Klerksdorp
South Africa THINK Pietermaritzburg KwaZulu Natal
South Africa CHRU, Empilweni TB Hospital Port Elizabeth
South Africa Setshaba Research Centre Soshanguve
Tanzania Ifakara Health Institute Bagamoyo
Tanzania NIMR-Mbeya Mbeya
Tanzania Kilimanjaro Clinical Research Institute Moshi
Tanzania Mwanza Intervention Trials Unit Mwanza
Uganda Case Western Reserve University Kampala

Sponsors (1)

Lead Sponsor Collaborator
Global Alliance for TB Drug Development

Countries where clinical trial is conducted

Brazil,  Georgia,  Malaysia,  Philippines,  Russian Federation,  South Africa,  Tanzania,  Uganda, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With Culture Negative Status by 8 Weeks Culture negative status is achieved when a participant produces at least two negative culture results at different visits (at least 7 days apart) without an intervening positive culture result for M.tb. Days 0-56 (8 weeks)
Secondary Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months) Unfavorable status:
Participants not classified as having achieved or maintained culture negative status when last seen
Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture
Participants who had a positive culture not followed by at least two negative cultures when last seen
Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide
Participants definitely or possibly dying from TB related cause during the follow-up phase
Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy
Participants lost to follow up or withdrawn from the study before end of treatment
52 weeks after start of therapy
Secondary Time to Culture Negative Status Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures, that point is considered culture negativity During treatment (17 or 26 weeks)
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