A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1

HIV-1 Clinical Trial

Official title:

A Phase 2b Multicenter, Randomized, Comparative Trial Of Uk-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleotide/Nucleoside Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced Hiv-1 Infected Subjects With Evidence Of Nnrti Resistant Hiv-1

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00823979
• Other study ID #: A5271022
• Secondary ID: 2007-004392-19
• Status: Terminated
• Phase: Phase 2
• Start date: March 25, 2009
• Est. completion date: October 18, 2012

Study information

• Verified date: November 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 96 week study to determine if UK- 453,061 in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor is as efficacious, safe and tolerable as etravirine in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor in HIV-1 infected patients who have been previously treated with antiretroviral drugs and have NNRTI resistance mutations.

Description:

The trial was terminated on 12 April, 2012 due to lack of efficacy at the Week 24 analysis. The decision to terminate the trial was not based on any safety concerns.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 105
• Est. completion date: October 18, 2012
• Est. primary completion date: October 18, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female at least 18 years of age available for a follow-up period of at least 96 weeks.

• HIV 1 RNA viral load of greater then 500 copies/mL.

• Negative urine pregnancy test.

Exclusion Criteria:

• Suspected or documented active, untreated HIV-1 related opportunistic infection or other condition requiring acute therapy at the time of randomization.

• Subjects with acute Hepatitis B and/or C within 30 days of randomization.

• Previous use of Darunavir or etravirine

Related Conditions & MeSH terms

• HIV-1

Intervention

Drug:
• UK-453,061 Dose 1
UK 453,061 750 mg QD + one optimized NRTI + darunavir/ritonavir.
• UK-453,061 Dose 2
UK 453,061 1000 mg QD + one optimized NRTI + darunavir/ritonavir.
• Etravirine
Etravirine 200 mg BID + one optimized NRTI + darunavir/ritonavir.

Locations

Country	Name	City	State
Brazil	Instituto de Infectologia Campinas	Campinas	SP
Brazil	Instituto A.Z. de Pesquisa e Ensino	Curitiba	PR
Brazil	Hospital Geral de Nova Iguacu	Nova Iguacu	RJ
Brazil	Hospital Nossa Senhora da Conceicao	PoA	RS
Brazil	Centro de Referencia e Treinamento DST/AIDS	Sao Paulo	SP
Brazil	Hospital Heliopolis	Sao Paulo	SP
Germany	Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin	Koeln
Italy	Unita' Operativa Malattie Infettive	Bologna
Italy	U.O.S. Immunologia Clinica	Roma
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Poland	Oddzial do Leczenia HIV	Szczecin
Poland	SPZOZ Wojewodzki Szpital Zakazny	Warszawa
Portugal	Hospitais da Universidade de Coimbra	Coimbra
Portugal	Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos	Lisboa
Portugal	Centro Hospitalar de Lisboa Ocidental, EPE.	Lisboa
Portugal	Hospital de Joaquim Urbano	Porto
Portugal	Hospital São João	Porto
Puerto Rico	Innovative Care PSC	Bayamon
Puerto Rico	Ararat Research Center	Ponce
Puerto Rico	University of Puerto Rico - Medical Sciences Campus - Puerto Rico Medical Center	Rio Piedras
Puerto Rico	HOPE Clinical Research	San Juan
Puerto Rico	UPR-CTU Pharmacy	San Juan
South Africa	Desmond Tutu HIV Foundation	Cape Town	Western CAPE
South Africa	Willowmead Medical Center	Cape Town	Western CAPE
South Africa	Dr. J Fourie Medical Centre	Dundee	Kwazulu-natal
South Africa	203 Maxwell Centre	Durban	Kwazulu-natal
South Africa	Soweto Clinical Trials Centre	Johannesburg	Gauteng
South Africa	University of Witwatersrand	Johannesburg	Gauteng
South Africa	Chris Hani Baragwanath Hospital	Soweto	Johannesburg
Spain	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Taiwan	Department of Infectious Disease, E-Da Hospital	Kaohsiung County
Taiwan	Veterans General Hospital - Taipei	Taipei
Ukraine	Vinnitsa Regional center for AIDS Prevention and Control	Berezyna	Vinnitsa District, Vinnitsa Region
Ukraine	Donetsk Regional Center of AIDSs prophylaxis and control	Donetsk
Ukraine	Lugansk Regional Center of AIDS prophylaxis and control	Lugansk
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton	EAST Sussex
United Kingdom	North Manchester General Hospital	Crumpsall	Greater Manchester
United Kingdom	Royal Infirmary GUM Clinic	Edinburgh
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Free Hospital	London
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Saint Hope Foundation - Bellaire Clinic	Bellaire	Texas
United States	Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Saint Hope Foundation - Conroe Clinic	Conroe	Texas
United States	Nicholaos C. Bellos, MD, PA	Dallas	Texas
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Nassau University Medical Center	East Meadow	New York
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Jeffrey Goodman Special Care Clinic	Los Angeles	California
United States	Office of Anthony Mills, MD, Inc.	Los Angeles	California
United States	Care Resource	Miami	Florida
United States	The Kinder Medical Group	Miami	Florida
United States	Greiger Clinic	Mount Vernon	New York
United States	Orlando Immunology Center	Orlando	Florida
United States	Infectious Diseases Associates of Northwest Florida, PA	Pensacola	Florida
United States	CARES	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	San Francisco Veterans Affairs Medical Center	San Francisco	California
United States	Saint Hope Foundation - Stafford Clinic	Stafford	Texas
United States	Hillsborough County Health Department	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Brazil,  Germany,  Italy,  Malaysia,  Poland,  Portugal,  Puerto Rico,  South Africa,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24	Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).	Week 24
Secondary	Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96	Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).	Weeks 48, 96
Secondary	Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96	Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).	Week 24, 48, 96
Secondary	Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96	Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). For the log10 scale, all the HIV-1 RNA levels were log10 transformed prior to the average calculations. Baseline value calculated as average of measurements collected prior to and including Day 1 pre-dose.	Baseline, Week 24, 48, 96
Secondary	Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96	TAD was calculated as (area under the curve of HIV-1 RNA levels [log10 copies/mL] from baseline to the time point of interest divided by time period in weeks) minus baseline HIV-1 RNA level (log10 copies/mL). Baseline value calculated as average of measurements collected at prior to and including Day 1 pre-dose. Due to early termination of the study decision was made not to derive TAD results for Week 96.	Week 24, 48, 96
Secondary	Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96	TLOVR50 response (50 denotes lower limit of quantification [LLOQ] of assay=50 copies/mL): compliment to TLOVR50 failure. TLOVR50 failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of drug; lost to follow-up; new ARV drug; met treatment failure [TF] criteria). TF: an increase of at least (>=)3 times the baseline plasma HIV-1 RNA level at Week 2 or thereafter; failure to achieve HIV-1 RNA level <50 copies/mL at Week 24; starting at Week 2, an increase in HIV-1 RNA level to detectable levels (>50 copies/mL); HIV-1 RNA <1 log10 decrease from baseline at Week 4 or thereafter. TF were confirmed by second measurement >=14 days after first. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.	Week 24, 48, 96
Secondary	Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96	Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.	Baseline, Week 24, 48, 96
Secondary	Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96	Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.	Baseline, Week 24, 48, 96
Secondary	Number of Participants With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Resistance-Associated Mutations (RAMs) and/or Phenotypic Susceptibility at Time of Treatment Failure Through Week 48	Genotypic and phenotypic resistance to NNRTIs based on International Acquired Immunodeficiency Syndrome (AIDS) Society, United States of America (IAS-USA) RAM guidelines were evaluated using Monogram Biosciences PhenoSenseGT Assay at Baseline. This was then repeated for all participants with HIV-1 viral load >500 copies/mL at treatment failure, up to Week 48.	Baseline through Week 48
Secondary	Number of Participants With Laboratory Test Abnormalities	Laboratory analysis included blood chemistry, hematology and urinalysis.	Baseline up to Week 48 or early termination
Secondary	Population Pharmacokinetics (PK) of Lersivirine	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48
Secondary	Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)	Simple quartile exposure analysis of success rate (viral load <50 copies/mL) versus median Cmin assesses the exposure response relationship. Percentage of participants with HIV-1 RNA level <50 copies/mL at median Cmin quartile were planned to be reported.	Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48