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HIV InfectionsPhase 3NCT00540449

TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

A Phase 3 study testing TMC278 and Efavirenz in people with HIV Infections and HIV-1, run by Tibotec Pharmaceuticals, Ireland at 92 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a fixed background regimen consisting of emtricitabine (FTC) + tenofovir disoproxil fumarate (TDF), in HIV-1… Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
TMC278 and Efavirenz
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
694 participants
Where
92 sitesin 20 countries
Study dates
May 2008to Dec 2011
Phase
Phase 3
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 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient with documented HIV-1 infection
  • Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening
  • Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure)
  • Patient's virus is sensitive to TDF and FTC
  • Patient agrees not to start ART (antiretroviral treatment) before the baseline visit

Who cannot join

  • Previous use of ANY ARV drug for ANY length of time
  • Any documented evidence of NNRTI resistance associated mutations in patient's HIV
  • Category C AIDS defining illness, except: stable Kaposi Sarcoma, wasting syndrome if not progressive
  • Pneumocystis carinii pneumonia (PCP) that is considered not cured
  • Active TB
  • Allergy or hypersensitivity to study or background ARTs
  • Specific grade 3 or 4 toxicity
  • Kidney impairment: calculated creatinine clearance <50 ml/min

Trial locations and contacts

92 sites in 20 countries.

92 sites in 20 countries

United States32 sites

  • Study site

    Akron, Ohio

  • Study site

    Albany, New York

  • Study site

    Austin, Texas

  • Study site

    Baltimore, Maryland

  • Study site

    Beverly Hills, California

  • Study site

    Birmingham, Alabama

  • Study site

    Buffalo, New York

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Columbia, South Carolina

  • Study site

    Columbus, Ohio

  • Study site

    Dallas, Texas

  • Study site

    Durham, North Carolina

  • Study site

    Fort Lauderdale, Florida

  • Study site

    Los Angeles, California

  • Study site

    Macon, Georgia

  • Study site

    Miami, Florida

  • Study site

    Milwaukee, Wisconsin

  • Study site

    New York, New York

  • Study site

    Newark, New Jersey

  • Study site

    Newport Beach, California

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Phoenix, Arizona

  • Study site

    Portland, Oregon

  • Study site

    Sacramento, California

  • Study site

    Seattle, Washington

  • Study site

    Tampa, Florida

  • Study site

    Vero Beach, Florida

  • Study site

    Washington D.C., District of Columbia

  • Study site

    West Palm Beach, Florida

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

South Africa6 sites

  • Study site

    Bloemfontein

  • Study site

    Cape Town

  • Study site

    Durban

  • Study site

    Houghton, Johannesburg

  • Study site

    Johannesburg

  • Study site

    Pretoria

Other trials in South Africa

Brazil5 sites

  • Study site

    Curitiba

  • Study site

    Nova Iguaçu

  • Study site

    Rio de Janeiro

  • Study site

    Salvador

  • Study site

    São Paulo

Other trials in Brazil

France5 sites

  • Study site

    Loiré

  • Study site

    Lyon

  • Study site

    Paris

  • Study site

    Tourcoing

  • Study site

    Villejuif

Other trials in France

Australia4 sites

  • Study site

    Darlinghurst

  • Study site

    Melbourne

  • Study site

    Perth

  • Study site

    Surry Hills

Other trials in Australia

Portugal4 sites

  • Study site

    Amadora

  • Study site

    Lisbon

  • Study site

    Portimão

  • Study site

    Porto

Other trials in Portugal

Taiwan4 sites

  • Study site

    Kaohsiung City

  • Study site

    Kaohsiung County

  • Study site

    Tainan

  • Study site

    Taipei

Other trials in Taiwan

Argentina3 sites

  • Study site

    Buenos Aires

  • Study site

    Córdoba

  • Study site

    Guernica

Other trials in Argentina

Canada3 sites

  • Study site

    Montreal, Quebec

  • Study site

    Ottawa, Ontario

  • Study site

    Toronto, Ontario

Other trials in Canada

Denmark3 sites

  • Study site

    Copenhagen

  • Study site

    Hvidovre

  • Study site

    Odense

Other trials in Denmark

Romania3 sites

  • Study site

    Bucharest

  • Study site

    Iași

  • Study site

    Timișoara

Other trials in Romania

Spain3 sites

  • Study site

    Alicante

  • Study site

    Barcelona

  • Study site

    Madrid

Other trials in Spain

Sweden3 sites

  • Study site

    Gothenburg

  • Study site

    Malmö

  • Study site

    Stockholm

Other trials in Sweden

Thailand3 sites

  • Study site

    Bangkok

  • Study site

    Chiang Mai

  • Study site

    Khon Kaen

Other trials in Thailand

United Kingdom3 sites

  • Study site

    Birmingham

  • Study site

    Brighton

  • Study site

    London

Other trials in United Kingdom

Austria2 sites

  • Study site

    Innsbruck

  • Study site

    Vienna

Other trials in Austria

Mexico2 sites

  • Study site

    Mexico City

  • Study site

    Zapopan

Other trials in Mexico

Russia2 sites

  • Study site

    Krasnodar

  • Study site

    Saint Petersburg

Other trials in Russia

Netherlands1 site

  • Study site

    Rotterdam

Other trials in Netherlands

Puerto Rico1 site

  • Study site

    San Juan

Other trials in Puerto Rico

About this study

Official title: A Phase III, Randomized, Double-blind Trial of TMC278 25 mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Fixed Background Regimen Consisting of Tenofovir Disoproxil Fumarate and Emtricitabine in Antiretroviral-naive HIV-1 Infected Subjects.

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a fixed background regimen consisting of emtricitabine (FTC) + tenofovir disoproxil fumarate (TDF), in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics, medical resource utilization and treatment adherence.

Read the detailed description

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned to TMC278 or to efavirenz, either of these treatments will be in combination with two other anti-HIV drugs (2 NRTIs: emtricitabine (FTC) + tenofovir (TDF)). TDF/FTC will be administered as a fixed dose combination if available. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL) in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg once daily plus one tablet of placebo once daily that looks just like efavirenz (EFV) plus tenofovir/emtricitabine; Control Group: One tablet of Placebo once daily that looks just like TMC278 plus EFV 600 mg once daily plus tenofovir/emtricitabine.

Being tested
TMC278, Efavirenz
Keywords
TMC278-C209, Antiretroviral, Non-nucleoside reverse transcriptase inhibitor, HIV-1, AIDS, TMC278-TiDP6-C209, Treatment Naive
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

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

  • TMC278Drug

    25 mg tablet once daily for 96 weeks

  • EfavirenzDrug

    600mg once daily for 96 weeks

Study groups in NCT00540449
Study groupRoleWhat they receive
EfavirenzActive comparatorEfavirenz 600mg once daily for 96 weeks
Receives: Drug: Efavirenz
TMC278ExperimentalTMC278 25 mg tablet once daily for 96 weeks
Receives: Drug: TMC278

What is being measured

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

  1. Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48

    Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).

    Measured: Week 48

Secondary outcomes (8)

  1. The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48

    The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol.

    Measured: Week 48

  2. Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96

    Measured: Week 96

  3. The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96

    Measured: Week 96

  4. Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96).

    Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per ml at the last on-treatment visit (post-Week 96).

    Measured: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit

  5. Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48

    Measured: Week 48

  6. Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96

    Measured: Week 96

  7. Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data)

    Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.

    Measured: Baseline, Week 48, and Week 96

  8. Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure

    Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).

    Measured: Week 96

Timeline

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

  1. First posted8 Oct 2007 (estimated)
  2. Study startMay 2008
  3. Primary completionFeb 2010
  4. Study completionDec 2011

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
694 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00540449
Sponsor's protocol ID
CR002689
Other IDs
TMC278-TIDP6-C209
Status last verified
Feb 2016
First submitted
4 Oct 2007
Last updated
29 Mar 2016
Data monitoring committee
Yes

Publications

  • Rimsky L, Van Eygen V, Hoogstoel A, Stevens M, Boven K, Picchio G, Vingerhoets J. 96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials. Antivir Ther. 2013;18(8):967-77. doi: 10.3851/IMP2636. Epub 2013 May 28.

    PubMed 23714781

  • Nelson M, Amaya G, Clumeck N, Arns da Cunha C, Jayaweera D, Junod P, Li T, Tebas P, Stevens M, Buelens A, Vanveggel S, Boven K; ECHO and THRIVE Study Groups. Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials. J Antimicrob Chemother. 2012 Aug;67(8):2020-8. doi: 10.1093/jac/dks130. Epub 2012 Apr 24.

    PubMed 22532465

  • Molina JM, Cahn P, Grinsztejn B, Lazzarin A, Mills A, Saag M, Supparatpinyo K, Walmsley S, Crauwels H, Rimsky LT, Vanveggel S, Boven K; ECHO study group. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.

    PubMed 21763936

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TMC278 and Efavirenz in people with HIV Infections and HIV-1, run by Tibotec Pharmaceuticals, Ireland at 92 sites in 20 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 5 inclusion and 8 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: finished, as of the sponsor's last update on 29 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in United States, South Africa, Brazil, France, Australia and 15 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 11 Jul 2011). 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?

Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 (time frame: Week 48). 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 NCT00540449, which also lists 3 linked publications.

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 29 Mar 2016.

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