GePheRal: Clinical Validation of the Genotypic Diagnosis of NCT01381328

Clinical Trial Details — Status: Recruiting

Administrative data
NCT number	NCT01381328
Other study ID #	Gepheral
Secondary ID	Merck Sharp & Do
Status	Recruiting
Phase	N/A
First received	June 23, 2011
Last updated	February 8, 2013
Start date	December 2011
Est. completion date	September 2013

Study information
Verified date	February 2013
Source	Università Vita-Salute San Raffaele
Contact	Antonella Castagna, MD
Phone	0039022643
Email	castagna.antonella[@]hsr.it
Is FDA regulated	No
Health authority	Italy: Ethics Committee
Study type	Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility
Status	Recruiting
Enrollment	100
Est. completion date	September 2013
Est. primary completion date	March 2013
Accepts healthy volunteers	No
Gender	Both
Age group	18 Years and older
Eligibility	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:

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

Locations
Country	Name	City	State
Italy	Department of Infectious Diseases, IRCCS San Raffaele Hospital	Milan

Sponsors *(3)*
Lead Sponsor	Collaborator
Università Vita-Salute San Raffaele	IRCCS San Raffaele, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Italy,

References & Publications (13)

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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):1261-9. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov. 2005 Mar;4(3):236-48. Review. — View Citation

Sichtig N, Sierra S, Kaiser R, Däumer M, Reuter S, Schülter E, Altmann A, Fätkenheuer 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome
Type	Measure	Time frame	Safety issue
Primary	- mean value of fold-change resistance determined by the phenotypic assay at baseline	baseline	No
Secondary	changes of fold-change resistance determined by the phenotypic assay with respect to baseline.	24 and 48 hours, W1, W2, W3 and W4 upon discontinuation	No
Secondary	genetic changes under continuous drug pressure or drug discontinuation with respect to baseline(dynamics of the reversion of resistance mutations)	24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.	No
Secondary	changes of the replication capacity with respect to baseline	24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.	No
Secondary	changes of HIV-RNA with respect to baseline	24 and 48 hours, W1, W2, W3 and W4 upon discontinuation	No
Secondary	changes in CD4, CD4%, CD8, CD8% with respect to baseline	24 and 48 hours, W1, W2, W3 and W4 upon discontinuation	No

GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance

Clinical Trial Details — Status: Recruiting

Administrative data

Study information

Clinical Trial Summary

Description:

Recruitment information / eligibility

Study Design

Related Conditions & MeSH terms

Locations

Sponsors (3)

Country where clinical trial is conducted

References & Publications (13)

Outcome