- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01381328
GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance
February 8, 2013 updated by: Elisabetta Carini, Università Vita-Salute San Raffaele
The purpose of this study is to correlate the different patterns of resistance mutations observed in vivo in patients failing RAL treatment with the fold-change resistance determined by the phenotypic assay.
Study Overview
Status
Unknown
Detailed Description
The secondary objectives are, as follows:
- to establish standardised genotypic assay for the HIV-1 pol gene region (region of interest, sensitivity, mutations involved as primary or compensatory changes, role of polymorphism present at baseline).
- to reach consensus on the algorithm interpretation of in house ex-vivo genotypic evaluations.
- to assess the genetic changes in RAL-failing patients under continuous drug pressure or drug discontinuation (dynamics of the reversion of resistance mutations).
- to evaluate in RAL resistant HIV-1 variants the changes in replication capacity (RC) (baseline vs. following-timepoints).
- to evaluate the immunological and virological trend associated with a raltegravir-regimen failure.
Study Type
Observational
Enrollment (Anticipated)
100
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Antonella Castagna, MD
- Phone Number: 7934 0039022643
- Email: castagna.antonella@hsr.it
Study Contact Backup
- Name: Elisabetta Carini, MSc
- Phone Number: 7934 0039022643
- Email: carini.elisabetta@hsr.it
Study Locations
-
-
-
Milan, Italy, 20127
- Recruiting
- Department of Infectious Diseases, IRCCS San Raffaele Hospital
-
Contact:
- Antonella Castagna, MD
- Phone Number: 7934 0039022643
- Email: castagna.antonella@hsr.it
-
Contact:
- Elisabetta Carini, MSc
- Phone Number: 7934 0039022643
- Email: carini.elisabetta@hsr.it
-
Principal Investigator:
- Antonella Castagna, MD
-
Principal Investigator:
- Massimo Clementi, Prof.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
primary care clinic
Description
Inclusion Criteria:
- Adult (at least 18 years of age) treatment-experienced, HIV-infected subjects of either sex and of any race, failing to a RAL-containing regimen will be enrolled in the study
Exclusion Criteria:
- none
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
---|
RAL Group
HIV-1 infected patients failing to a RALTEGRAVIR-containing regimen
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
- mean value of fold-change resistance determined by the phenotypic assay at baseline
Time Frame: baseline
|
baseline
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
changes of fold-change resistance determined by the phenotypic assay with respect to baseline.
Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
|
24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
|
genetic changes under continuous drug pressure or drug discontinuation with respect to baseline(dynamics of the reversion of resistance mutations)
Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
|
24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
|
changes of the replication capacity with respect to baseline
Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
|
24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
|
changes of HIV-RNA with respect to baseline
Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
|
24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
|
changes in CD4, CD4%, CD8, CD8% with respect to baseline
Time Frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
|
24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Massimo Clementi, Prof., University Vita-Salute San Raffaele Laboratory of Microbiology and Virology
- Study Director: Antonella Castagna, MD, Department of Infectious Diseases, IRCCS San Raffaele Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.
- Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65. doi: 10.1056/NEJMoa0708978.
- Engelman A, Mizuuchi K, Craigie R. HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell. 1991 Dec 20;67(6):1211-21. doi: 10.1016/0092-8674(91)90297-c.
- Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov. 2005 Mar;4(3):236-48. doi: 10.1038/nrd1660.
- Anker M, Corales RB. Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. doi: 10.1517/13543784.17.1.97.
- Canducci F, Sampaolo M, Marinozzi MC, Boeri E, Spagnuolo V, Galli A, Castagna A, Lazzarin A, Clementi M, Gianotti N. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS. 2009 Feb 20;23(4):455-60. doi: 10.1097/QAD.0b013e328323da60.
- Nakahara K, Wakasa-Morimoto C, Kobayashi M, Miki S, Noshi T, Seki T, Kanamori-Koyama M, Kawauchi S, Suyama A, Fujishita T, Yoshinaga T, Garvey EP, Johns BA, Foster SA, Underwood MR, Sato A, Fujiwara T. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Antiviral Res. 2009 Feb;81(2):141-6. doi: 10.1016/j.antiviral.2008.10.007. Epub 2008 Nov 21.
- Kobayashi M, Nakahara K, Seki T, Miki S, Kawauchi S, Suyama A, Wakasa-Morimoto C, Kodama M, Endoh T, Oosugi E, Matsushita Y, Murai H, Fujishita T, Yoshinaga T, Garvey E, Foster S, Underwood M, Johns B, Sato A, Fujiwara T. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res. 2008 Nov;80(2):213-22. doi: 10.1016/j.antiviral.2008.06.012. Epub 2008 Jul 14.
- Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, Perno CF. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev. 2009 Jan-Mar;11(1):17-29.
- Malet I, Delelis O, Valantin MA, Montes B, Soulie C, Wirden M, Tchertanov L, Peytavin G, Reynes J, Mouscadet JF, Katlama C, Calvez V, Marcelin AG. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother. 2008 Apr;52(4):1351-8. doi: 10.1128/AAC.01228-07. Epub 2008 Jan 28.
- Menzo S, Monachetti A, Balotta C, Corvasce S, Rusconi S, Paolucci S, Baldanti F, Bagnarelli P, Clementi M. Processivity and drug-dependence of HIV-1 protease: determinants of viral fitness in variants resistant to protease inhibitors. AIDS. 2003 Mar 28;17(5):663-71. doi: 10.1097/01.aids.0000050852.71999.5f.
- Sichtig N, Sierra S, Kaiser R, Daumer M, Reuter S, Schulter E, Altmann A, Fatkenheuer G, Dittmer U, Pfister H, Esser S. Evolution of raltegravir resistance during therapy. J Antimicrob Chemother. 2009 Jul;64(1):25-32. doi: 10.1093/jac/dkp153. Epub 2009 May 14.
- Malet I, Delelis O, Soulie C, Wirden M, Tchertanov L, Mottaz P, Peytavin G, Katlama C, Mouscadet JF, Calvez V, Marcelin AG. Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. J Antimicrob Chemother. 2009 Apr;63(4):795-804. doi: 10.1093/jac/dkp014. Epub 2009 Feb 16.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2011
Primary Completion (Anticipated)
March 1, 2013
Study Completion (Anticipated)
September 1, 2013
Study Registration Dates
First Submitted
June 23, 2011
First Submitted That Met QC Criteria
June 24, 2011
First Posted (Estimate)
June 27, 2011
Study Record Updates
Last Update Posted (Estimate)
February 11, 2013
Last Update Submitted That Met QC Criteria
February 8, 2013
Last Verified
February 1, 2013
More Information
Terms related to this study
Other Study ID Numbers
- Gepheral
- Merck Sharp & Dohme Corp. (Other Identifier: Merck Sharp & Dohme Corp.)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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