AzTrials
AzTrials

HIV InfectionsPhase 3NCT00543725

TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

A Phase 3 study testing TMC278 and efavirenz in people with HIV Infections and HIV-1, run by Tibotec Pharmaceuticals, Ireland at 82 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 background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of… Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
HIV Infections, HIV-1
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
680 participants
Where
82 sitesin 20 countries
Study dates
Jun 2008to Feb 2012
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 the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment
  • Patient agrees not to start ART before the baseline visit
  • Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment regimen.

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

82 sites in 20 countries.

82 sites in 20 countries

United States25 sites

  • Study site

    Atlantis, Florida

  • Study site

    Baltimore, Maryland

  • Study site

    Boston, Massachusetts

  • Study site

    Chicago, Illinois

  • Study site

    Dallas, Texas

  • Study site

    Detroit, Michigan

  • Study site

    Flushing, New York

  • Study site

    Houston, Texas

  • Study site

    Lexington, Kentucky

  • Study site

    Long Beach, California

  • Study site

    Longview, Texas

  • Study site

    Los Angeles, California

  • Study site

    Miami, Florida

  • Study site

    Miami Beach, Florida

  • Study site

    Minneapolis, Minnesota

  • Study site

    New York, New York

  • Study site

    Newark, New Jersey

  • Study site

    Orlando, Florida

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Rochester, New York

  • Study site

    San Francisco, California

  • Study site

    Springfield, Massachusetts

  • Study site

    Tampa, Florida

  • Study site

    The Bronx, New York

  • Study site

    Washington D.C., District of Columbia

Other trials in United States

Germany7 sites

  • Study site

    Berlin

  • Study site

    Cologne

  • Study site

    Essen

  • Study site

    Frankfurt

  • Study site

    Hamburg

  • Study site

    Hanover

  • Study site

    Mannheim

Other trials in Germany

South Africa6 sites

  • Study site

    Bloemfontein

  • Study site

    Cape Town

  • Study site

    Dundee

  • Study site

    Johannesburg

  • Study site

    Pretoria

  • Study site

    Westdene Johannesburg Gauteng

Other trials in South Africa

Brazil5 sites

  • Study site

    Campinas

  • Study site

    Distrito Barao Geraldo-Campina

  • Study site

    Pinheiros

  • Study site

    Recife

  • Study site

    São Paulo

Other trials in Brazil

Canada5 sites

  • Study site

    Calgary, Alberta

  • Study site

    Montreal, Quebec

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

  • Study site

    Winnipeg, Manitoba

Other trials in Canada

Belgium4 sites

  • Study site

    Antwerp

  • Study site

    Brussels

  • Study site

    Ghent

  • Study site

    Leuven

Other trials in Belgium

France4 sites

  • Study site

    Clamart

  • Study site

    Le Kremlin-Bicêtre

  • Study site

    Montpellier

  • Study site

    Paris

Other trials in France

Russia4 sites

  • Study site

    Moscow

  • Study site

    Saint Petersburg

  • Study site

    Smolensk

  • Study site

    Voronezh

Other trials in Russia

Australia3 sites

  • Study site

    Darlinghurst

  • Study site

    Prahran

  • Study site

    Surry Hills

Other trials in Australia

China3 sites

  • Study site

    Beijing

  • Study site

    Guangzhou

  • Study site

    Shanghai

Other trials in China

Spain3 sites

  • Study site

    Barcelona

  • Study site

    Elche

  • Study site

    Madrid

Other trials in Spain

Chile2 sites

  • Study site

    Providencia

  • Study site

    Santiago

Other trials in Chile

India2 sites

  • Study site

    Chennai

  • Study site

    Nagpur

Other trials in India

Mexico2 sites

  • Study site

    Guadalajara

  • Study site

    Mexico City

Other trials in Mexico

United Kingdom2 sites

  • Study site

    London

  • Study site

    Manchester

Other trials in United Kingdom

Costa Rica1 site

  • Study site

    San José

Other trials in Costa Rica

Panama1 site

  • Study site

    Panama City

Other trials in Panama

Portugal1 site

  • Study site

    Porto

Other trials in Portugal

Puerto Rico1 site

  • Study site

    San Juan

Other trials in Puerto Rico

Thailand1 site

  • Study site

    Bangkok

Other trials in Thailand

About this study

Official title: A Phase III, Randomized, Double-blind Trial of TMC278 25mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Background Regimen Containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors 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 background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) 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 and 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 (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. 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 daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.

Being tested
TMC278, efavirenz
Keywords
Antiretroviral, HIV-1, AIDS, TMC278-C215, TMC278-TiDP6-C215, 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

    600 mg tablet once daily for 96 weeks

Study groups in NCT00543725
Study groupRoleWhat they receive
002Active comparatorefavirenz 600 mg tablet once daily for 96 weeks
Receives: Drug: efavirenz
001ExperimentalTMC278 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 Per 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. Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 Wk 48 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 Per mL) at Week 96

    Measured: Week 96

  3. Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 post-Week 96 visit.

    Measured: Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz

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

    Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/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 >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).

    Measured: Week 48

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

    Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 96. 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 >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).

    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 Determinations by Developing 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 posted15 Oct 2007 (estimated)
  2. Study startJun 2008
  3. Primary completionJan 2010
  4. Study completionFeb 2012

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
680 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00543725
Sponsor's protocol ID
CR002704
Other IDs
TMC278-TIDP6-C215
Status last verified
Mar 2016
First submitted
11 Oct 2007
Last updated
1 Apr 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

  • Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, Ruxrungtham K, Wu H, Zorrilla C, Crauwels H, Rimsky LT, Vanveggel S, Boven K; THRIVE study group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011 Jul 16;378(9787):229-37. doi: 10.1016/S0140-6736(11)60983-5.

    PubMed 21763935

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 82 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 6 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 1 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 82 sites in United States, Germany, South Africa, Brazil, Canada 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 12 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 Per 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 NCT00543725, 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 1 Apr 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in