Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201408000858108 Date of Approval: 22/07/2014
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title NC-006
Official scientific title A Phase 3 Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin plus PA-82 plus Pyrazinamide after 4 and 6 months of Treatment in Adult Subjects with Drug-Sensitive Smear-Positive Pulmonary Tuberculosis and after 6 months of Treatment in Adult Subjects with Multi-Drug Resistant, Smear-Positive Pulmonary Tuberculosis
Brief summary describing the background and objectives of the trial The trial aims to demonstrate that the experimental regimen administered for either 4 or 6 months to subjects with DS-TB is not inferior to the standard 6 month control regimen using a non-inferiority margin of 12%. Primary Objectives Assess the efficacy, safety and tolerability of: ¿ moxifloxacin 400mg plus PA-824100mg plus pyrazinamide 1500mg regimen after 4 months of treatment, ¿ moxifloxacin 400mg plus PA-824 200mg plus pyrazinamide 1500mg regimen after 4 months of treatment, ¿ moxifloxacin 400mg plus PA-824 200mg plus pyrazinamide 1500mg regimen after 6 months of treatment in subjects with DS pulmonary TB compared to standard HRZE treatment
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Acronym
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 03/11/2014
Actual trial start date
Anticipated date of last follow up 03/05/2018
Actual Last follow-up date
Anticipated target sample size (number of participants) 1500
Actual target sample size (number of participants)
Recruitment status Suspended
Publication URL
Secondary Ids Issuing authority/Trial register
3795 SANCTR
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomisation - stratification with minimisation using IVRS Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group M-Pa-Z 400mg/200mg/1500mg Moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg daily 17 weeks Tablets 300
Control Group HRZE / HR Daily: RHZE Weeks 1-8: 30-39kg: 2 tabs; 40-54kg: 3 tabs; 55 ¿ 70kg: 4 tabs; > 71kg: 5 tabs. RH Weeks 9-26: 30-39kg: 2 tabs; 40-54Kg: 3 tabs; 55-70 kg: 4 tabs; > 71kg: 5 tabs. 26 weeks RHZE 150 mg/75 mg/400 mg/275 mg combination tabs daily for 2 months followed by RH 150 mg/75 mg combination tablets daily for 4 months. 300 Historical
Experimental Group M-Pa-Z 400mg/100mg/1500mg Moxifloxacin 400 mg + PA-824 100 mg + pyrazinamide 1500 mg daily 17 weeks Moxifloxacin 400 mg + PA-824 100 mg + pyrazinamide 1500 mg daily for 17 weeks 300
Experimental Group M-Pa-Z 400mg/200mg/1500mg MDR-TB Moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg daily 26 weeks Moxifloxacin 400 mg + PA-824 100 mg + pyrazinamide 1500 mg daily for 17 weeks 300
Experimental Group M-Pa-Z 400mg/200mg/1500mg Moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg daily 26 weeks Moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg daily for 26 weeks 300
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures. 2. Male or female, aged 18 years or over. 3. Body weight (in light clothing and no shoes) ¿ 30 kg. 4. Sputum positive for tubercule bacilli (at least 1+ on the IUATLD/WHO scale (Appendix 1)) on smear microscopy at the trial laboratory. 5. Drug-Sensitive TB treatment arms subjects should be: a. sensitive to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid) AND b. either newly diagnosed for TB or have a patient history of being untreated for at least 3 years after cure from a previous episode of TB. If they are entered into the trial due to being sensitive to rifampicin by rapid sputum based test, however on receipt of the rifampicin resistance testing using an indirect susceptibility test in liquid culture this shows they are rifampicin resistant, they will be: a. Excluded as late exclusions; b. Possibly replaced as determined by the sponsor. MDR-TB treatment arm subjects should be resistant to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid). 6. A chest x-ray which in the opinion of the investigator is compatible with pulmonary TB. 7. Be of non-childbearing potential or using effective methods of birth control. 1. Any non TB related condition that could compromise the well-being of the subject. 2. Being or about to be treated for Malaria. 3. Is critically ill & has a diagnosis likely to result in death. 4. TB meningitis or other forms of extrapulmonary TB 5. History of allergy or hypersensitivity to any of the trial IMP 6. For HIV infected subjects any of the following: a. CD4+ count <100 cells/µL; b. Karnofsky score <60%; c. Received IV antifungal medication < 90 days ago; d. WHO Clinical Stage 4 HIV. 7. Resistant to fluoroquinolones. 8. Resistant to pyrazinamide. 9. Participated in other trials with IP within 8 weeks prior to trial start. 10. Subjects with any of the following at screening: a. Cardiac arrhythmia requiring medication; b. Prolongation of QT/QTc interval with QTcF >450 ms; c. History of additional risk factors for Torsade de Pointes: d. Any clinically significant ECG abnormality. 11. Unstable Diabetes Mellitus which required hospitalization for hyper- or hypo-glycaemia within the past year prior to screening. 12. Previous treatment with PA-824. 13. For DS-TB: Previous treatment for tuberculosis within 3 years prior to screening. For the MDR-TB: Previous treatment for MDR-TB. 14. Any diseases in which the use of the std TB drugs is contra-indicated. 15. Use of any drug within 30 days prior to randomisation known to prolong QTc interval. 16. Use of systemic glucocorticoids <1 year of screening. 17. Subjects recently started or needing to start ART within 1 month after randomization. 18. Subjects with the following toxicities at screening as defined by DMID adult toxicity table: a. creatinine >/= grade 2 b. CrCl level < 30 mLs/min c. haemoglobin grade 4; d. platelets >/= grade 3 e. serum potassium < the lower limit of normal f. AST >/= grade 3 g. ALT >/= grade 3 h. ALP grade 4 i. total bilirubin: o > 2.0 x ULN, when other liver functions are in the normal range o >1.50 x ULN when accompanied by any increase in other liver function tests 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 06/06/2014 Wits Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
8 Blackwood Avenue Johannesburg 2176 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 01/07/2014 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
E 52, Room 24, Old Main Building, Groote Schuur Hospital, Observatory Cape Town South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 22/08/2014 Ifakara Health Institute Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
P O BOX 78373 DAR ES SALAAM Dar-es-Salaam Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 03/09/2014 Mbeya Medical Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P.O. Box 419, Mbeya Mbeya Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 27/08/2014 Kilimanjaro Christian Medical Centre Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P. O. Box 2240 MOSHI. Moshi Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 02/09/2014 University of Makerere SBS Institutional Review Board,
Ethics Committee Address
Street address City Postal code Country
Kampala Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 08/08/2014 University of Zambia Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus, P.O. Box 50110, Lusaka Lusaka Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 06/08/2014 KEMRI
Ethics Committee Address
Street address City Postal code Country
PO Box 54850, Nairobi Nairobi Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Incidence of bacteriologic failure or relapse or clinical failure at 12 months from the start of therapy 12 months
Secondary Outcome Safety and Tolerability Various
Secondary Outcome Mycobacterial Characterization Various
Secondary Outcome Pharmacokinetics (PK) and Pharmacokinetics-Pharmacodynamics (PK-PD): Various
Secondary Outcome Mycobacterial Characterization Various
Secondary Outcome Pharmacokinetics (PK) and Pharmacokinetics-Pharmacodynamics (PK-PD): Various
Secondary Outcome Efficacy various
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre for Infectious Disease Research in Zambia (CIDRZ) Great North Road Lusaka Zambia
The Aurum Institute, Gavin J. Churchyard Legacy Centre Cnr Margaretha Prinsloo and OR Tambo Drive Klerksdorp 2570 South Africa
The Aurum Institute, Rustenburg Research Centre 50 Steen Street, Cnr Pretorius Street Rustenburg 0300 South Africa
Synexus SA Stanza Clinical Research Centre Pretoria 0122 South Africa
University of the Witwatersrand, Clinical HIV Research Unit (CHRU) DS-TB Perth Road, Westdene Johannesburg 2000 South Africa
University of the Witwatersrand, Clinical HIV Research Unit (CHRU) MDR-TB Perth Road, Westdene Johannesburg 2000 South Africa
UCT Lung Institute George Street, Mowbray Cape Town 7700 South Africa
The Aurum Institute, Tembisa Clinical Research Centre, Tembisa Hospital Cnr RTJ Namane and Flint Mazibuko Drive, Hospital View Tembisa 1736 South Africa
TASK Clinical Research Centre Smal Street, Belville Cape Town 7000 South Africa
THINK Beatrice Street Durban 4000 South Africa
Ifakara Health Institute (IHI) Mwananyamala Regional Hospital Ingusure street Dar-es-Salaam Tanzania
Klerksdorp Tshepong Hospital, MDR Unit Benji Olifant Road, Jouberton Klerksdorp 2571 South Africa
Enhancing Care Foundation, Durban International Clinical Research Site Ward D1, Wentworth Hospital, Sidmouth Avenue Durban 4000 South Africa
Madibeng Centre for Research 40 Pienaar Street, Brits North West 0250 South Africa
Setshaba Research Centre 2088 Block H, Soshanguve Pretoria 0152 South Africa
Uganda Case Western Reserve University Research Collaboration, TB Clinic Annex Old Mulago Hill Road, Kampala Uganda
Mbeya Medical Research Programme (MMRP) Mbeya Referral Hospital Hill Mbeya Tanzania
National Institute for Medical Research (NIMR) Isamilo Road Mwanza Tanzania
Kilimanjaro Clinical Research Institute (KCRI) Kilimanjaro Christian Medical Centre Moshi Tanzania
Kenya Medical Research Institute (KEMRI) Kenyatta National Hospital Nairobi Kenya
Centre for Respiratory Disease Research (CRDR), Kenyatta National Hospital Nairobi Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Global Alliance for TB Drug Development 40 Wall Street New York 10005 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Global Alliance for TB Drug Development 40 Wall Street New York 10005 United States of America Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Dr Stephen H Gillespie Medical and Biological Sciences Building University of St. Andrews North Haugh, St. Andrews Fife KY 16 9TF United Kingdom
University College London (UCL) Gower Street London United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Andreas Diacon ahd@sun.ac.za 021 917 1044 1 Small Street, Bellville
City Postal code Country Position/Affiliation
Cape Town 7000 South Africa National Principal Investigator
Role Name Email Phone Street address
Public Enquiries Mary-Anne Bopape Mary-Anne.Bopape@triclinium.net +27118830206 135 West Street, Sandown
City Postal code Country Position/Affiliation
Johannesburg 2196 South Africa Regulatory Affairs
Role Name Email Phone Street address
Scientific Enquiries Dan Everitt dan.everitt@tballiance.org +1 646 616 8671 40 Wall Street, 24th Floor
City Postal code Country Position/Affiliation
New York 10005 United States of America Sponsor Physician
REPORTING
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Result URL Hyperlinks
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