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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

3 maart 2016 bijgewerkt door: Tibotec Pharmaceuticals, Ireland

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

680

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Australië
      • Darlinghurst, Australië
      • Prahran, Australië
      • Surry Hills, Australië
  • België
      • Antwerpen, België
      • Brussels, België
      • Gent, België
      • Leuven, België
  • Brazilië
      • Campinas, Brazilië
      • Distrito Barao Geraldo-Campina, Brazilië
      • Pinheiros, Brazilië
      • Recife, Brazilië
      • Sao Paulo, Brazilië
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Chili
      • Providencia, Chili
      • Santiago, Chili
  • China
      • Beijing, China
      • Guangzhou, China
      • Shanghai, China
  • Costa Rica
      • San Jose, Costa Rica
  • Duitsland
      • Berlin, Duitsland
      • Essen, Duitsland
      • Frankfurt, Duitsland
      • Hamburg, Duitsland
      • Hannover, Duitsland
      • Köln, Duitsland
      • Mannheim, Duitsland
  • Frankrijk
      • Clamart, Frankrijk
      • Le Kremlin Bicetre, Frankrijk
      • Montpellier, Frankrijk
      • Paris, Frankrijk
  • Indië
      • Chennai, Indië
      • Nagpur, Indië
  • Mexico
      • Guadalajara N/A, Mexico
      • Mexico City, Mexico
  • Panama
      • Panama, Panama
      • Panama City N/A, Panama
  • Portugal
      • Porto, Portugal
  • Puerto Rico
      • San Juan, Puerto Rico
  • Russische Federatie
      • Moscow N/A, Russische Federatie
      • Saint-Petersburg, Russische Federatie
      • Smolensk, Russische Federatie
      • Voronezh, Russische Federatie
  • Spanje
      • Barcelona, Spanje
      • Barcelona N/A, Spanje
      • Elche, Spanje
      • Madrid, Spanje
  • Thailand
      • Bangkok, Thailand
  • Verenigd Koninkrijk
      • London, Verenigd Koninkrijk
      • Manchester, Verenigd Koninkrijk
  • Verenigde Staten
    • California
      • Long Beach, California, Verenigde Staten
      • Los Angeles, California, Verenigde Staten
      • San Francisco, California, Verenigde Staten
    • District of Columbia
      • Washington, District of Columbia, Verenigde Staten
    • Florida
      • Atlantis, Florida, Verenigde Staten
      • Miami, Florida, Verenigde Staten
      • Miami Beach, Florida, Verenigde Staten
      • Orlando, Florida, Verenigde Staten
      • Tampa, Florida, Verenigde Staten
    • Illinois
      • Chicago, Illinois, Verenigde Staten
    • Kentucky
      • Lexington, Kentucky, Verenigde Staten
    • Maryland
      • Baltimore, Maryland, Verenigde Staten
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten
      • Springfield, Massachusetts, Verenigde Staten
    • Michigan
      • Detroit, Michigan, Verenigde Staten
    • Minnesota
      • Minneapolis, Minnesota, Verenigde Staten
    • New Jersey
      • Newark, New Jersey, Verenigde Staten
    • New York
      • Bronx, New York, Verenigde Staten
      • Flushing, New York, Verenigde Staten
      • New York, New York, Verenigde Staten
      • Rochester, New York, Verenigde Staten
    • Pennsylvania
      • Philadelphia, Pennsylvania, Verenigde Staten
    • Texas
      • Dallas, Texas, Verenigde Staten
      • Houston, Texas, Verenigde Staten
      • Longview, Texas, Verenigde Staten
  • Zuid-Afrika
      • Bloemfontein, Zuid-Afrika
      • Cape Town, Zuid-Afrika
      • Dundee, Zuid-Afrika
      • Johannesburg, Zuid-Afrika
      • Pretoria N/A, Zuid-Afrika
      • Westdene Johannesburg Gauteng, Zuid-Afrika

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 99 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: 002
efavirenz 600 mg tablet once daily for 96 weeks
Geneesmiddel: efavirenz
600 mg tablet once daily for 96 weeks
Experimenteel: 001
TMC278 25 mg tablet once daily for 96 weeks
Geneesmiddel: TMC278
25 mg tablet eenmaal daags gedurende 96 weken

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48
Tijdsspanne: 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).
Week 48

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Gemiddelde verandering van baseline tot week 48 en week 96 in absoluut en relatief aantal CD4+-cellen (met behulp van geïmputeerde gegevens)
Tijdsspanne: Basislijn, week 48 en week 96
Verandering ten opzichte van baseline in aantal CD4+-cellen werd geïmputeerd in geval van ontbrekende waarden: in geval van voortijdige stopzetting werden gegevens geïmputeerd met de baselinewaarde na stopzetting (d.w.z. verandering=0, niet-voltooid [NC] = mislukt); anders werd de laatste overgedragen waarneming toegepast.
Basislijn, week 48 en week 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48
Tijdsspanne: 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.
Week 48
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96
Tijdsspanne: Week 96
Week 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96
Tijdsspanne: Week 96
Week 96
Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96).
Tijdsspanne: Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
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.
Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 48
Tijdsspanne: 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).
Week 48
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 96
Tijdsspanne: 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).
Week 96
Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
Tijdsspanne: Week 96
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).
Week 96

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2008

Primaire voltooiing (Werkelijk)

1 januari 2010

Studie voltooiing (Werkelijk)

1 februari 2012

Studieregistratiedata

Eerst ingediend

11 oktober 2007

Eerst ingediend dat voldeed aan de QC-criteria

11 oktober 2007

Eerst geplaatst (Schatting)

15 oktober 2007

Updates van studierecords

Laatste update geplaatst (Schatting)

1 april 2016

Laatste update ingediend die voldeed aan QC-criteria

3 maart 2016

Laatst geverifieerd

1 maart 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • CR002704
  • TMC278-TIDP6-C215 (Andere identificatie: Tibotec Pharmaceuticals, Ireland)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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