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

NCT03338621 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SimpliciTB (B-Pa-M-Z) NC-008
• Study Type: interventional
• Target: 455
• Locations: 8 countries
• Sites: 26

Brief 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)

Conditions

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

Keywords

tuberculosis; drug-resistant tuberculosis; TB; DR-TB; pretomanid; PA-824; bedaquiline; TMC207; moxifloxacin; pyrazinamide; HRZE; TB Alliance; NC-008; drug-sensitive tuberculosis; DS-TB

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months)

  52 weeks after start of therapy

• Time to Culture Negative Status

  During treatment (17 or 26 weeks)

Study Arms (3)

Drug Sensitive BPaMZ

EXPERIMENTAL

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

Drug: Pretomanid; Drug: Bedaquiline; Drug: Moxifloxacin; Drug: Pyrazinamide

Drug Sensitive Standard Treatment

ACTIVE COMPARATOR

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

Drug: HRZE; Drug: HR

Drug Resistant BPaMZ

EXPERIMENTAL

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)

Drug: Pretomanid; Drug: Bedaquiline; Drug: Moxifloxacin; Drug: Pyrazinamide

Interventions

Pretomanid DRUG

200 mg tablets

Also known as: PA-824, Pa

Drug Resistant BPaMZ; Drug Sensitive BPaMZ

Bedaquiline DRUG

100 mg tablets

Also known as: B, TMC207

Drug Resistant BPaMZ; Drug Sensitive BPaMZ

Moxifloxacin DRUG

400 mg tablets

Also known as: M

Drug Resistant BPaMZ; Drug Sensitive BPaMZ

Pyrazinamide DRUG

500 mg tablets

Also known as: Z

Drug Resistant BPaMZ; Drug Sensitive BPaMZ

HRZE DRUG

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

Also known as: isoniazid, rifampicin, ethambutol

Drug Sensitive Standard Treatment

HR DRUG

isoniazid 75 mg plus rifampicin 150 mg combination tablets

Also known as: isoniazid, rifampicin

Drug Sensitive Standard Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (26)

Evandro Chagas

Rio de Janeiro, Brazil

Location

FIOCRUZ

Rio de Janeiro, Brazil

Location

National Center for Tuberculosis and Lung Diseases

Tbilisi, 0101, Georgia

Location

Institut Perubatan Respiratori

Kuala Lumpur, Malaysia

Location

Lung Center of Philippines

Manila, 1104, Philippines

Location

Tropical Disease Foundation

Manila, 1230, Philippines

Location

Moscow City Research and Practice Tuberculosis Treatment Centre

Moscow, 107014, Russia

Location

Central TB Research Institute of the Federal Agency of Scientific Organizations

Moscow, 107564, Russia

Location

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

Moscow, 119991, Russia

Location

Research Institute of the Phthisiopulmonology

Saint Petersburg, 191036, Russia

Location

Ural Research Institute of Phthisiopulmonology

Yekaterinburg, 620039, Russia

Location

THINK

Pietermaritzburg, KwaZulu-Natal, 3216, South Africa

Location

Madibeng Centre for Research

Brits, 0250, South Africa

Location

TASK

Cape Town, 7530, South Africa

Location

University of Cape Town Lung Institute

Cape Town, 7700, South Africa

Location

Enhancing Care Foundation

Durban, 4001, South Africa

Location

CHRU, King Dinuzulu

Durban, 4015, South Africa

Location

CHRU, Helen Joseph Hospital

Johannesburg, 2092, South Africa

Location

PHRU, Tshepong Hospital

Klerksdorp, 2571, South Africa

Location

CHRU, Empilweni TB Hospital

Port Elizabeth, 7070, South Africa

Location

Setshaba Research Centre

Soshanguve, 0152, South Africa

Location

Ifakara Health Institute

Bagamoyo, Tanzania

Location

NIMR-Mbeya

Mbeya, Tanzania

Location

Kilimanjaro Clinical Research Institute

Moshi, Tanzania

Location

Mwanza Intervention Trials Unit

Mwanza, Tanzania

Location

Case Western Reserve University

Kampala, 2109, Uganda

Location

Related Publications (1)

• 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.

  PMID: 38768617 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Tuberculosis

Interventions

pretomanid; bedaquiline; Moxifloxacin; Pyrazinamide; Isoniazid; Rifampin; Ethambutol

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines

Results Point of Contact

• Title: Morounfolu Olugbosi
• Organization: TB Alliance

morounfolu.olugbosi@tballiance.org

1 212 227 7540

Study Officials

• Morounfolu Olugbosi, MD MSc

  Global Alliance for TB Drug Development

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 9, 2017
• Study Start: July 30, 2018
• Primary Completion: July 1, 2021
• Study Completion: June 10, 2022
• Last Updated: March 7, 2024
• Results First Posted: November 8, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data is expected to become available in mid-2024.
• Access Criteria: Researchers must agree to the Terms and Conditions for Use of the TB-PACTS data platform and submit an online application form to request access to the data platform.

Locations

ZA (10); MY (1); GE (1); UG (1); PH (2); BR (2); RU (5); TA (4)