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

Tuberculosis Clinical Trial

Official title:

An Open-Label, Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of a 4-month Treatment of Bedaquiline Plus Pretomanid Plus Moxifloxacin Plus Pyrazinamide (BPaMZ) Compared to a 6-month Treatment of HRZE/HR (Control) in Adult Participants With Drug-Sensitive Smear-Positive Pulmonary Tuberculosis (DS-TB) and a 6-month Treatment of BPaMZ in Adult Participants With Drug Resistant, Smear-Positive Pulmonary Tuberculosis (DR-TB)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03338621
• Other study ID #: SimpliciTB (B-Pa-M-Z) NC-008
• Status: Completed
• Phase: Phase 2/Phase 3
• 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
• 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

Related Conditions & MeSH terms

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

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)