Trial profile and progress overview (by March 30 th , 2011)
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Transcript of Trial profile and progress overview (by March 30 th , 2011)
1ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Trial profile Trial profile
and progress overviewand progress overview
(by March 30(by March 30th th , 2011), 2011)
2ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
INCLUSIONSINCLUSIONS
− 1st patient enrolled in France : July 30th, 2009
− 1st patient enrolled in Brazil : February 22th, 2010
− End of inclusions is postponed to July 2011
10 patients to be included per month 150 patients
Trial profile and progress overviewTrial profile and progress overview
3ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Brazilian Sites (1)
Rio de Janeiro – Beatriz Grinsztejn Laboratório de Pesquisa Clínica em DST e Aids - IPEC / FIOCRUZ- Inclusion (prevision) 30 patients- Pharmacokinetic, Immunological and Genetic Sub-studies yes- Site Initiation (prevision) december, 2009
4ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Brazilian Sites (2)
Nova Iguaçu – José Henrique PilottoDepartamento de DST – Hospital Geral de Nova Iguaçu- Inclusion (prevision) 30 patients- Pharmacokinetic, Immunological and Genetic Sub-studies yes- Site Initiation (prevision) january, 2010
5ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Brazilian Sites (3)
São Paulo – Jose Valdez MadrugaCentro de Referência e Treinamento em DST/Aids – SES/SP- Inclusion (prevision) 25 patients- Pharmacokinetic and Immunological Sub-studies no- Genetic Sub-study yes- Site Initiation (prevision) january, 2010
6ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Brazilian Sites (4)
Porto Alegre – Nêmora BarcelosServiço de Atenção Terapêutica – Hospital Sanatório Partenon- Inclusion (prevision) 25 patients- Pharmacokinetic and Immunological Sub-studies no- Genetic Sub-study yes- Site Initiation (prevision) january, 2010
7ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Brazilian Sites (5)
Salvador – Carlos BritesLaboratório de Pesquisa Clínica em Infectologia – Hospital Universitário Prof. Edgar Santos - Inclusion (prevision) 25 patients- Pharmacokinetic and Immunological Sub-studies no- Genetic Sub-study yes- Site Initiation (prevision) january, 2010
8ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Brazilian Sites (6)
• Hospital Conceição• Dr Breno Riegel Santos• Inclusion (prevision) 20 patients
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Brasil Coordinating site activities
• Clinical Sites identification and contact• Financial agreements with the sites• Conduction of local regulatory process• Conduction of Drug importation and distribution to the clinical
sites• Laboratory contracts development• Protocol training(lab,eCRFs,pharmacy)• Site initiation • Randomization• Site monitoring• Assistance with any protocol related issues• Repository
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ANVISA Submissions and Approvals (Protocol and Import License)
• Submission Date 30/07/2009• Registration Error at ANVISA 09/09/2009• New registration 09/09/2009• First questions received from ANVISA
10/11/2009• Answers protocolled at ANVISA 18/11/2009• Protocol and import license approval (prevision)
dezembro/2009
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First Training Performed (1)
• Date: 24 and 25/09/2009, in Rio de Janeiro
• Participants:- Brazilian PI- Brazilian Coordination- Subinvestigators, study coordinators and pharmacists of all sites - Loboratory cooordinators- Central Pharmacy Team
12ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
First Training Performed (2)
Activities:• Presentation :
– protocol– study operational precedures– estimates of the patients inclusions – laboratory procedures– randomization procedures
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First Training Performed (3)
• Presentation:– management medication procedures– central pharmacy procedures– SAEs report procedures– capture System– CRF– monitoring procedures
14ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Initiation Visit at Sites (1)
• Visit performed by Project Manager, Monitor, Data Manager, Pharmacyst and Laboratory Coordinator
• Visits took place in the clinical department, all laboratories and the hospital pharmacy
• ANRS opening of clinical sites procedures were formalized
15ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Initiation Visit at Sites (2)
• The following issues were reviewed:– study operational precedures– laboratory procedures– randomization procedures– management medication procedures– central pharmacy procedures– SAEs report procedures– monitoring procedures
16ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Initiation Visit at Sites (3)
• eCRF training was performed
• Site Initiation prevision:Rio de Janeiro december, 2009Nova Iguaçu, São Paulo, Porto
Alegreand Salvador january/february,
2010
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Pre-inclusions and inclusions curves Pre-inclusions and inclusions curves
• In France:
18ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Pre-inclusions and inclusions curvesPre-inclusions and inclusions curves
• In Brazil:
19ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Pre-inclusions and inclusions curvesPre-inclusions and inclusions curves • In Brazil and in France (until July 2011):
1st enrollment in France 1st enrollment in Brazil
20ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Number of randomized patients per month Number of randomized patients per month
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Pre-included N = 149
France N = 8
Brazil N = 141
To be included into the analysis N = 124
Excluded from the analysis N = 0
Randomized N = 124
France N = 8
Brazil N = 116
Treated N = 124
Non treated N = 0
Lost to follow up N = 2
withdrawal N = 3
Strategy discontinuation N = 6
Non included N = 17
France N = 0
Brazil N = 17
Flow diagram of ANRS 12 180 REFLATE TB trial Flow diagram of ANRS 12 180 REFLATE TB trial data by 30 March 2011data by 30 March 2011
23ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Withdrawal(s) – Lost to follow up - Strategy discontinuation Withdrawal(s) – Lost to follow up - Strategy discontinuation
− Withdrawals : N=3
− Lost-to-follow up : N=2
− Strategy discontinuations : N=6
• anti-TB : N=2
• ARV : N=3
• ARV and anti-TB : N=1
24ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Sub-studies enrolmentSub-studies enrolment
Trial profile and progress overviewTrial profile and progress overview
25ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Pharmacokinetic sub-study • Objectives
– To study the pharmacokinetic interactions between rifampin and raltegravir (at the doses of either 400 mg bid and 800 mg bid
Endpoint
– Evolution of pharmacokinetic parameters of raltegravir between week 4 (with rifampin) and at least 1 month after rifampin discontinuation (before dose decrease for patients in the raltegravir 800 mg arm)
26ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Immunological sub-study • Objective
– To assess the incidence of immune reconstitution inflammatory syndrome (IRIS) and to identify potential predictors of IRIS
• Endpoint
– Rate and predictors of immune reconstitution inflammatory syndrome (IRIS)
40 patients planned by the protocol43 patients have been includedInclusions were stopped in October 2010
27ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Genetic sub-study
• Objective : To assess relationship between genetic polymorphism of genes
involved in the metabolization and transport of ARV or anti-TB drugs (UGT1A1, CYP2B6, acetylase, MDR1) and plasma concentrations, efficacy and tolerance
By March 30th , 2011 :
120 patients agreed (and 4 disagreed) to participate so far
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PRESENTING REFLATE TB RESULTS PRESENTING REFLATE TB RESULTS
• 19th Conference on Retroviruses and Opportunistic Infections (CROI) :
- on February-March 2012
- Late breaker abstract on January 2012 (= last patient inclusion should be in June 2011)
• XIX International AIDS Conference :
- on 22-27 July 2012 (Washington DC, USA)
- Abstract submission will open towards the end of 2011
• 52th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) :
- on September 2012
- Abstract soumission deadline : May 2012
Different possibilities (depending on patient recruitment and conference deadlines)
29ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
INSERM-Bordeaux
• Implementation of eCRF• Excellent day by day protocol
management• Excellent level of communication and
trouble shooting
30ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
ANRS
• All steps implemented so far came along very smoothly
• Nice scientific environment and partnership
31ANRS 12 180 REFLATE TB SC meeting – 5 April 2011
Challenges
• Finalize enrollment within the planned timeframe
• Keep very low levels of LFU• Funding for substudies• Next projects?