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HIV-1Phase 2NCT00823979

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

A Phase 2 study testing UK-453,061 Dose 1, UK-453,061 Dose 2 and Etravirine in people with HIV-1, run by Pfizer at 63 sites in 13 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV-1
What is being tested?
UK-453,061 Dose 1, UK-453,061 Dose 2 and Etravirine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
63 sitesin 13 countries
Study dates
25 Mar 2009to 18 Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

63 sites in 13 countries.

63 sites in 13 countries

United States21 sites

  • AIDS Research Consortium of Atlanta

    Atlanta, Georgia, 30308

  • Saint Hope Foundation - Bellaire Clinic

    Bellaire, Texas, 77401

  • Ruth M. Rothstein CORE Center

    Chicago, Illinois, 60612

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267-0405

  • Saint Hope Foundation - Conroe Clinic

    Conroe, Texas, 77301

  • Nicholaos C. Bellos, MD, PA

    Dallas, Texas, 75204

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75235

  • Nassau University Medical Center

    East Meadow, New York, 11554

  • Rosedale Infectious Diseases

    Huntersville, North Carolina, 28078

  • Jeffrey Goodman Special Care Clinic

    Los Angeles, California, 90028

  • Office of Anthony Mills, MD, Inc.

    Los Angeles, California, 90069

  • The Kinder Medical Group

    Miami, Florida, 33133

  • Care Resource

    Miami, Florida, 33137

  • Greiger Clinic

    Mount Vernon, New York, 10550

  • Orlando Immunology Center

    Orlando, Florida, 32803

  • Infectious Diseases Associates of Northwest Florida, PA

    Pensacola, Florida, 32504

  • CARES

    Sacramento, California, 95814

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • San Francisco Veterans Affairs Medical Center

    San Francisco, California, 94121

  • Saint Hope Foundation - Stafford Clinic

    Stafford, Texas, 77477

  • Hillsborough County Health Department

    Tampa, Florida, 33602

Other trials in United States

South Africa7 sites

  • Willowmead Medical Center

    Cape Town, Western Cape, 7780

  • Desmond Tutu HIV Foundation

    Cape Town, Western Cape, 7925

  • Dr. J Fourie Medical Centre

    Dundee, KwaZulu-Natal, 3000

  • 203 Maxwell Centre

    Durban, KwaZulu-Natal, 4001

  • Soweto Clinical Trials Centre

    Johannesburg, Gauteng, 1818

  • University of Witwatersrand

    Johannesburg, Gauteng, 2193

  • Chris Hani Baragwanath Hospital

    Soweto, Johannesburg, 2013

Other trials in South Africa

Brazil6 sites

  • Instituto de Infectologia Campinas

    Campinas, São Paulo, 13015-080

  • Instituto A.Z. de Pesquisa e Ensino

    Curitiba, Paraná, 80240-280

  • Hospital Geral de Nova Iguacu

    Nova Iguaçu, Rio de Janeiro, 26030-381

  • Hospital Nossa Senhora da Conceicao

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Centro de Referencia e Treinamento DST/AIDS

    São Paulo, São Paulo, 04121-000

  • Hospital Heliopolis

    São Paulo, São Paulo, 04231-030

Other trials in Brazil

Portugal5 sites

  • Hospitais da Universidade de Coimbra

    Coimbra, 3000-075

  • Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos

    Lisbon, 1169-050

  • Centro Hospitalar de Lisboa Ocidental, EPE.

    Lisbon, 1349-019

  • Hospital São João

    Porto, 4200-319

  • Hospital de Joaquim Urbano

    Porto, 4369-004

Other trials in Portugal

Puerto Rico5 sites

  • Innovative Care PSC

    Bayamón, 00959

  • Ararat Research Center

    Ponce, 00717-1563

  • University of Puerto Rico - Medical Sciences Campus - Puerto Rico Medical Center

    Rio Piedras, 00935

  • UPR-CTU Pharmacy

    San Juan, PR, 00935

  • HOPE Clinical Research

    San Juan, 00909

Other trials in Puerto Rico

United Kingdom5 sites

  • Brighton and Sussex University Hospitals NHS Trust

    Brighton, EAST Sussex, BN2 1ES

  • North Manchester General Hospital

    Crumpsall, Greater Manchester, M8 5RB

  • Royal Infirmary GUM Clinic

    Edinburgh, EH3 9HA

  • Western General Hospital

    Edinburgh, EH4 2XU

  • Royal Free Hospital

    London, NW3 2QG

Other trials in United Kingdom

Ukraine3 sites

  • Vinnitsa Regional center for AIDS Prevention and Control

    Berezyna, Vinnitsa District, Vinnitsa Region, 23222

  • Donetsk Regional Center of AIDSs prophylaxis and control

    Donetsk, 83045

  • Lugansk Regional Center of AIDS prophylaxis and control

    Luhansk, 91045

Other trials in Ukraine

Italy2 sites

  • Unita' Operativa Malattie Infettive

    Bologna, 40138

  • U.O.S. Immunologia Clinica

    Roma, 00184

Other trials in Italy

Malaysia2 sites

  • Hospital Raja Perempuan Zainab II

    Kota Bharu, Kelantan, 15586

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

Other trials in Malaysia

Poland2 sites

  • Oddzial do Leczenia HIV

    Szczecin, 71-455

  • SPZOZ Wojewodzki Szpital Zakazny

    Warsaw, 01-201

Other trials in Poland

Spain2 sites

  • Hospital Universitari Germans Trias I Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitario La Paz

    Madrid, 28046

Other trials in Spain

Taiwan2 sites

  • Department of Infectious Disease, E-Da Hospital

    Kaohsiung County, 82445

  • Veterans General Hospital - Taipei

    Taipei

Other trials in Taiwan

Germany1 site

  • Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin

    Cologne, 50937

Other trials in Germany

About this study

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

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.

Read the detailed 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.

Conditions
HIV-1
Being tested
UK-453,061 Dose 1, UK-453,061 Dose 2, Etravirine
Keywords
HIV-1 NNRTI Treatment Experienced, may have Protease inhibitor experience

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UK-453,061 Dose 1Drug

    UK 453,061 750 mg QD + one optimized NRTI + darunavir/ritonavir.

  • UK-453,061 Dose 2Drug

    UK 453,061 1000 mg QD + one optimized NRTI + darunavir/ritonavir.

  • EtravirineDrug

    Etravirine 200 mg BID + one optimized NRTI + darunavir/ritonavir.

Study groups in NCT00823979
Study groupRoleWhat they receive
UK- 453,061 Dose OneExperimentalNot described
Receives: Drug: UK-453,061 Dose 1
UK- 453,061 Dose TwoExperimentalNot described
Receives: Drug: UK-453,061 Dose 2
ComparatorActive comparatorNot described
Receives: Drug: Etravirine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Week 24

Secondary outcomes (11)

  1. 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).

    Measured: Weeks 48, 96

  2. 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).

    Measured: Week 24, 48, 96

  3. 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.

    Measured: Baseline, Week 24, 48, 96

  4. 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.

    Measured: Week 24, 48, 96

  5. 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.

    Measured: Week 24, 48, 96

  6. 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.

    Measured: Baseline, Week 24, 48, 96

  7. 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.

    Measured: Baseline, Week 24, 48, 96

  8. 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.

    Measured: Baseline through Week 48

  9. Number of Participants With Laboratory Test Abnormalities

    Laboratory analysis included blood chemistry, hematology and urinalysis.

    Measured: Baseline up to Week 48 or early termination

  10. 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.

    Measured: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

  11. 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.

    Measured: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2009 (estimated)
  2. Study start25 Mar 2009
  3. Primary completion18 Oct 2012
  4. Study completion18 Oct 2012

Why it stopped: See termination reason in detailed description.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00823979
Sponsor's protocol ID
A5271022
Other IDs
2007-004392-19
Status last verified
Nov 2018
First submitted
15 Jan 2009
Last updated
4 Dec 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing UK-453,061 Dose 1, UK-453,061 Dose 2 and Etravirine in people with HIV-1, run by Pfizer at 63 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in United States, South Africa, Brazil, Portugal, Puerto Rico and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00823979.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2018.

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