Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients

NCT ID: NCT03338621

Last Updated: 2024-03-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

455 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-30

Study Completion Date

2022-06-10

Brief Summary

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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)

Detailed Description

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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).

Conditions

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Tuberculosis, Pulmonary Tuberculosis, Multidrug-Resistant Tuberculosis, MDR Tuberculosis Drug-Resistant Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Drug Sensitive BPaMZ

Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months

Group Type EXPERIMENTAL

Pretomanid

Intervention Type DRUG

200 mg tablets

Bedaquiline

Intervention Type DRUG

100 mg tablets

Moxifloxacin

Intervention Type DRUG

400 mg tablets

Pyrazinamide

Intervention Type DRUG

500 mg tablets

Drug Sensitive Standard Treatment

isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26

Group Type ACTIVE_COMPARATOR

HRZE

Intervention Type DRUG

isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets

HR

Intervention Type DRUG

isoniazid 75 mg plus rifampicin 150 mg combination tablets

Drug Resistant BPaMZ

Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months)

Group Type EXPERIMENTAL

Pretomanid

Intervention Type DRUG

200 mg tablets

Bedaquiline

Intervention Type DRUG

100 mg tablets

Moxifloxacin

Intervention Type DRUG

400 mg tablets

Pyrazinamide

Intervention Type DRUG

500 mg tablets

Interventions

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Pretomanid

200 mg tablets

Intervention Type DRUG

Bedaquiline

100 mg tablets

Intervention Type DRUG

Moxifloxacin

400 mg tablets

Intervention Type DRUG

Pyrazinamide

500 mg tablets

Intervention Type DRUG

HRZE

isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets

Intervention Type DRUG

HR

isoniazid 75 mg plus rifampicin 150 mg combination tablets

Intervention Type DRUG

Other Intervention Names

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PA-824 Pa B TMC207 M Z isoniazid rifampicin ethambutol isoniazid rifampicin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Global Alliance for TB Drug Development

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Morounfolu Olugbosi, MD MSc

Role: STUDY_CHAIR

Global Alliance for TB Drug Development

Locations

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Evandro Chagas

Rio de Janeiro, , Brazil

Site Status

FIOCRUZ

Rio de Janeiro, , Brazil

Site Status

National Center for Tuberculosis and Lung Diseases

Tbilisi, , Georgia

Site Status

Institut Perubatan Respiratori

Kuala Lumpur, , Malaysia

Site Status

Lung Center of Philippines

Manila, , Philippines

Site Status

Tropical Disease Foundation

Manila, , Philippines

Site Status

Moscow City Research and Practice Tuberculosis Treatment Centre

Moscow, , Russia

Site Status

Central TB Research Institute of the Federal Agency of Scientific Organizations

Moscow, , Russia

Site Status

Research Institute of Phthisiopulmonology of I. M. Sechenov First Moscow State Medical University

Moscow, , Russia

Site Status

Research Institute of the Phthisiopulmonology

Saint Petersburg, , Russia

Site Status

Ural Research Institute of Phthisiopulmonology

Yekaterinburg, , Russia

Site Status

THINK

Pietermaritzburg, KwaZulu-Natal, South Africa

Site Status

Madibeng Centre for Research

Brits, , South Africa

Site Status

TASK

Cape Town, , South Africa

Site Status

University of Cape Town Lung Institute

Cape Town, , South Africa

Site Status

Enhancing Care Foundation

Durban, , South Africa

Site Status

CHRU, King Dinuzulu

Durban, , South Africa

Site Status

CHRU, Helen Joseph Hospital

Johannesburg, , South Africa

Site Status

PHRU, Tshepong Hospital

Klerksdorp, , South Africa

Site Status

CHRU, Empilweni TB Hospital

Port Elizabeth, , South Africa

Site Status

Setshaba Research Centre

Soshanguve, , South Africa

Site Status

Ifakara Health Institute

Bagamoyo, , Tanzania

Site Status

NIMR-Mbeya

Mbeya, , Tanzania

Site Status

Kilimanjaro Clinical Research Institute

Moshi, , Tanzania

Site Status

Mwanza Intervention Trials Unit

Mwanza, , Tanzania

Site Status

Case Western Reserve University

Kampala, , Uganda

Site Status

Countries

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Brazil Georgia Malaysia Philippines Russia South Africa Tanzania Uganda

References

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Cevik M, Thompson LC, Upton C, Rolla VC, Malahleha M, Mmbaga B, Ngubane N, Abu Bakar Z, Rassool M, Variava E, Dawson R, Staples S, Lalloo U, Louw C, Conradie F, Eristavi M, Samoilova A, Skornyakov SN, Ntinginya NE, Haraka F, Praygod G, Mayanja-Kizza H, Caoili J, Balanag V, Dalcolmo MP, McHugh T, Hunt R, Solanki P, Bateson A, Crook AM, Fabiane S, Timm J, Sun E, Spigelman M, Sloan DJ, Gillespie SH; SimpliciTB Consortium. Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial. Lancet Infect Dis. 2024 Sep;24(9):1003-1014. doi: 10.1016/S1473-3099(24)00223-8. Epub 2024 May 17.

Reference Type DERIVED
PMID: 38768617 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SimpliciTB (B-Pa-M-Z) NC-008

Identifier Type: -

Identifier Source: org_study_id

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