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.: PACTR201205000383208 Date of Registration: 24/05/2012
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title PanACEA-MAMS-TB-01
Official scientific title A multiple arm, multiple stage (MAMS), phase 2, open label, randomized, controlled clinical trial to evaluate four treatment regimens including SQ109, two increased doses of rifampicin, and moxifloxacin in adult subjects with newly diagnosed, smear¿positive pulmonary tuberculosis
Brief summary describing the background and objectives of the trial This study is a multiple-arm, multiple-stage (MAMS), phase 2, open label, randomized, controlled clinical trial that will compare the efficacy and safety of four experimental four-drug regimens with a standard control regimen in patients with smear positive, pulmonary tuberculosis (TB). Patients will be randomly allocated to the control or one of the four experimental regimens in the ratio 2:1:1:1:1. Experimental regimens will be given for 12 weeks.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SQ109
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Other
Anticipated trial start date 11/01/2013
Actual trial start date 14/05/2013
Anticipated date of last follow up 22/09/2014
Actual Last follow-up date
Anticipated target sample size (number of participants) 372
Actual target sample size (number of participants) 365
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
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 Minimisation Open label Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, 275 mg ethambutol, Pyroxidine 25 mg, rifampicin 300 mg 12 weeks SQ109 low 62
Experimental Group Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg 150 mg rifampicin, 75 mg isoniazid and 400 mg pyrazinamide, SQ109 150mg, pyridoxine 25 mg 12 weeks SQ109 high 62
Experimental Group Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg RHZ=: 150 mg rifampicin, 75 mg isoniazid and 400 mg pyrazinamide, SQ109 150mg, pyridoxine 25 mg 12 weeks Rifampicin 20mg/kg, SQ109 high 62
Experimental Group Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400mg 150 mg rifampicin, 75 mg isoniazid and 400 mg pyrazinamide, moxifloxacin, pyridoxine25mg 12 weeks Rifampicin 20mg/kg, Moxifloxacin 400 mg 62
Control Group Control: HRZE isoniazid, rifampicin standard, pyrazinamide, ethambutol 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide and 275 mg ethambutol 12 weeks Active Comparator 124 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. The patient has given free, signed written or witnessed oral informed consent for study participation prior to all trial-related procedures, including HIV testing. ago. 2. The patient has a diagnosis of pulmonary TB. 3. An adequate sputum bacterial load is confirmed by a Ziehl-Neelsen stained smear in the study laboratory. 4. The patient has a valid rapid test result (GeneXpert MTB/RIF®) from the sputum positive for MTB complex, and indicating susceptibility to Rifampicin. 5. The patient is aged at least 18 years at the day of informed consent. 6. The patient has a body weight of at least 35 kg, but not more than 90 kg. 7. Female patients of childbearing potential must have a negative serum pregnancy test, and consent to practise an effective method of birth control until week 26. 8. Male patients must consent to use an effective contraceptive method, if their sexual partner(s) is/are of childbearing potential, and if they are not surgically sterile. 9. The patient has a firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during the treatment and follow-up period, or will be compliant to study schedule and follow-up in the discretion of the investigator. 1. Circumstances that raise doubt about free, uncoerced consent to study participation. 2. Poor General Condition. 3. The patient is pregnant or breast-feeding. 4. The patient has an HIV infection. 5. The patient has a known intolerance to any of the study drugs, or concomitant disorders or conditions for which SQ109, rifampicin, moxifloxacin, or standard TB treatment are contraindicated. 6. The patient has an history or evidence of clinically relevant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator. 7. History of previous TB within the last five years. 8. Laboratory: at screening one or more of the following abnormalities were observed for the patient in screening laboratory: AST and/or ALT activity >3x the upper limit of normal, serum total bilirubin level >2.5 times the upper limit of normal, Creatinine clearance (CrCl) level greater than 30 mls/min, Complete blood count with hemoglobin level <7.0 g/dL, Platelet count <50,000/mm3, Serum potassium below the lower level of normal 9. ECG findings in the screening ECG: QTcB and/or QTcF of >0.450 s, AV block with PR interval > 0.20 s, prolongation of the QRS complex over 120 milliseconds, other changes in the ECG that are clinically relevant as per discretion of the investigator. 10. The patient has had treatment with any other investigational drug within 1 month prior to enrolment. 11. Previous anti-TB treatment. 12. QT prolonging medications. 13. CYP 450 inducers/inhibitors: administration within 30 days prior to dosing. 18 Year(s) 150 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
Yes LMU EC
Ethics Committee Address
Street address City Postal code Country
Munich Germany
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
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
Yes UCT
Ethics Committee Address
Street address City Postal code Country
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
Yes Wits Ethics
Ethics Committee Address
Street address City Postal code Country
Johannesburg 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
Yes Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
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
Yes UCT
Ethics Committee Address
Street address City Postal code Country
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
Yes Wits Ethics
Ethics Committee Address
Street address City Postal code Country
Johannesburg 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 MCC
Ethics Committee Address
Street address City Postal code Country
Johannesburg 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
Yes Mbeya Local Ethics
Ethics Committee Address
Street address City Postal code Country
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
Yes IHI
Ethics Committee Address
Street address City Postal code Country
Bagamoyo 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
Yes Moshi
Ethics Committee Address
Street address City Postal code Country
Moshi Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to stable culture conversion to negative in liquid media defined as the time from enrolment to the first of two negative weekly sputum cultures without an intervening positive culture in liquid media. Time to stable culture conversion to negative in liquid media defined as the time from enrolment to the first of two negative weekly sputum cultures without an intervening positive culture in liquid media.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre for Tuberculosis Researh Innovation George Street Cape Town 7700 South Africa
Wits Health Consortium Perth Rod, Westdene Johannesburg 2092 South Africa
Ifakara Health Institute P.O. Box 74 Bagamoyo Tanzania
Centre for Tuberculosis Researh Innovation George Street Cape Town 7700 South Africa
NIMR - Mbeya Medical Research programme P.O. Box 2410 Mbeya Tanzania
TASK Applied Science, Krl Bremer Hospital M2 c/o Mike Pienaar Boulevard and Frans Conradie Avenue Bellville 7530 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
BMBF Hannoversche Strasse 28 - 30 Berlin 10115 Germany
EDCTC P.O. Box 93015 The Hague 2509AA Netherlands
Sequella, Inc. Medical Center Drive, Suite 200 Rockville, MD Rockville, MD 20850 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Prof. Karl Walter Jauch, Medical Director, Klinikum of the Universtiy of Munich Marchioninistrasse 15 Munich 81377 Germany University
COLLABORATORS
Name Street address City Postal code Country
Prof. Andreas Diacon, Prinicipal Investigator c/o Mike Pienaar Boulevard and Frans Conradie Avenue Bellville 7530 South Africa
Prof. Gibson Kibiki PO Box 2236 Moshi Tanzania
Dr. Rodney Dawson, Co-PI George Street Cape Town 7700 South Africa
Dr. Nyanda Elias Ntinginya P.O. box 2410 Mbeya Tanzania
Dr. Lilian Tina Minja P.O. Box 74 Bagamoyo Tanzania
Dr. Karla Mellet Perth road, Westdene Johannesburg 2092 South Africa
Dr. Nomagugu Ndlovu Aurum house, The Ridge, 29 Queens Road, Parktown Johannesburg 2193 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Martin Boeree m.boeree@uccz.umcn.nl ++31246859284 Nijmeegsebaan 31
City Postal code Country Position/Affiliation
Groesbeek 6560 AB Netherlands Chief Investigator
Role Name Email Phone Street address
Public Enquiries Anna-Maria Mekota mekota@lrz.uni-muenchen.de +4989218017617 Georgenstr. 5
City Postal code Country Position/Affiliation
Munich 80799 Germany Project manager
Role Name Email Phone Street address
Scientific Enquiries Norbert Heinrich heinrich@lrz.uni-muenchen.de +4989218017601 Georgenstr. 5
City Postal code Country Position/Affiliation
Munich 80799 Germany Seniro Scientist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information