Clinical trial NCT03338621: Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
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
Lead sponsor: Global Alliance for TB Drug Development
Sponsor class: OTHER
First posted: 2017-11-09
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants
Primary purpose: TREATMENT

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)

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Culture Negative Status by 8 Weeks
timeFrame: Days 0-56 (8 weeks)
Secondary outcomes:
measure: Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months)
timeFrame: 52 weeks after start of therapy
measure: Time to Culture Negative Status
timeFrame: During treatment (17 or 26 weeks)
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Evandro Chagas
city: Rio de Janeiro
country: Brazil
facility: FIOCRUZ
city: Tbilisi
country: Georgia
facility: National Center for Tuberculosis and Lung Diseases
city: Kuala Lumpur
country: Malaysia
facility: Institut Perubatan Respiratori
city: Manila
country: Philippines
facility: Lung Center of Philippines
city: Manila
country: Philippines
facility: Tropical Disease Foundation
city: Moscow
country: Russian Federation
facility: Moscow City Research and Practice Tuberculosis Treatment Centre
city: Moscow
country: Russian Federation
facility: Central TB Research Institute of the Federal Agency of Scientific Organizations
city: Moscow
country: Russian Federation
facility: Research Institute of Phthisiopulmonology of I. M. Sechenov First Moscow State Medical University
city: Sankt Petersburg
country: Russian Federation
facility: Research Institute of the Phthisiopulmonology
city: Yekaterinburg
country: Russian Federation
facility: Ural Research Institute of Phthisiopulmonology
city: Pietermaritzburg
country: South Africa
facility: THINK
state: KwaZulu Natal
city: Brits
country: South Africa
facility: Madibeng Centre for Research
city: Cape Town
country: South Africa
facility: TASK
city: Cape Town
country: South Africa
facility: University of Cape Town Lung Institute
city: Durban
country: South Africa
facility: Enhancing Care Foundation
city: Durban
country: South Africa
facility: CHRU, King Dinuzulu
city: Johannesburg
country: South Africa
facility: CHRU, Helen Joseph Hospital
city: Klerksdorp
country: South Africa
facility: PHRU, Tshepong Hospital
city: Port Elizabeth
country: South Africa
facility: CHRU, Empilweni TB Hospital
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre
city: Bagamoyo
country: Tanzania
facility: Ifakara Health Institute
city: Mbeya
country: Tanzania
facility: NIMR-Mbeya
city: Moshi
country: Tanzania
facility: Kilimanjaro Clinical Research Institute
city: Mwanza
country: Tanzania
facility: Mwanza Intervention Trials Unit
city: Kampala
country: Uganda
facility: Case Western Reserve University
Study officials:
affiliation: Global Alliance for TB Drug Development
name: Morounfolu Olugbosi, MD MSc
role: STUDY_CHAIR
References: