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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 mars 2016 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

680

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Australien
      • Darlinghurst, Australien
      • Prahran, Australien
      • Surry Hills, Australien
  • Belgien
      • Antwerpen, Belgien
      • Brussels, Belgien
      • Gent, Belgien
      • Leuven, Belgien
  • Brasilien
      • Campinas, Brasilien
      • Distrito Barao Geraldo-Campina, Brasilien
      • Pinheiros, Brasilien
      • Recife, Brasilien
      • Sao Paulo, Brasilien
  • Chile
      • Providencia, Chile
      • Santiago, Chile
  • Costa Rica
      • San Jose, Costa Rica
  • Frankrike
      • Clamart, Frankrike
      • Le Kremlin Bicetre, Frankrike
      • Montpellier, Frankrike
      • Paris, Frankrike
  • Förenta staterna
    • California
      • Long Beach, California, Förenta staterna
      • Los Angeles, California, Förenta staterna
      • San Francisco, California, Förenta staterna
    • District of Columbia
      • Washington, District of Columbia, Förenta staterna
    • Florida
      • Atlantis, Florida, Förenta staterna
      • Miami, Florida, Förenta staterna
      • Miami Beach, Florida, Förenta staterna
      • Orlando, Florida, Förenta staterna
      • Tampa, Florida, Förenta staterna
    • Illinois
      • Chicago, Illinois, Förenta staterna
    • Kentucky
      • Lexington, Kentucky, Förenta staterna
    • Maryland
      • Baltimore, Maryland, Förenta staterna
    • Massachusetts
      • Boston, Massachusetts, Förenta staterna
      • Springfield, Massachusetts, Förenta staterna
    • Michigan
      • Detroit, Michigan, Förenta staterna
    • Minnesota
      • Minneapolis, Minnesota, Förenta staterna
    • New Jersey
      • Newark, New Jersey, Förenta staterna
    • New York
      • Bronx, New York, Förenta staterna
      • Flushing, New York, Förenta staterna
      • New York, New York, Förenta staterna
      • Rochester, New York, Förenta staterna
    • Pennsylvania
      • Philadelphia, Pennsylvania, Förenta staterna
    • Texas
      • Dallas, Texas, Förenta staterna
      • Houston, Texas, Förenta staterna
      • Longview, Texas, Förenta staterna
  • Indien
      • Chennai, Indien
      • Nagpur, Indien
  • Kanada
    • Alberta
      • Calgary, Alberta, Kanada
    • British Columbia
      • Vancouver, British Columbia, Kanada
    • Manitoba
      • Winnipeg, Manitoba, Kanada
    • Ontario
      • Toronto, Ontario, Kanada
    • Quebec
      • Montreal, Quebec, Kanada
  • Kina
      • Beijing, Kina
      • Guangzhou, Kina
      • Shanghai, Kina
  • Mexiko
      • Guadalajara N/A, Mexiko
      • Mexico City, Mexiko
  • Panama
      • Panama, Panama
      • Panama City N/A, Panama
  • Portugal
      • Porto, Portugal
  • Puerto Rico
      • San Juan, Puerto Rico
  • Ryska Federationen
      • Moscow N/A, Ryska Federationen
      • Saint-Petersburg, Ryska Federationen
      • Smolensk, Ryska Federationen
      • Voronezh, Ryska Federationen
  • Spanien
      • Barcelona, Spanien
      • Barcelona N/A, Spanien
      • Elche, Spanien
      • Madrid, Spanien
  • Storbritannien
      • London, Storbritannien
      • Manchester, Storbritannien
  • Sydafrika
      • Bloemfontein, Sydafrika
      • Cape Town, Sydafrika
      • Dundee, Sydafrika
      • Johannesburg, Sydafrika
      • Pretoria N/A, Sydafrika
      • Westdene Johannesburg Gauteng, Sydafrika
  • Thailand
      • Bangkok, Thailand
  • Tyskland
      • Berlin, Tyskland
      • Essen, Tyskland
      • Frankfurt, Tyskland
      • Hamburg, Tyskland
      • Hannover, Tyskland
      • Köln, Tyskland
      • Mannheim, Tyskland

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 99 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Aktiv komparator: 002
efavirenz 600 mg tablet once daily for 96 weeks
Läkemedel: efavirenz
600 mg tablet once daily for 96 weeks
Experimentell: 001
TMC278 25 mg tablet once daily for 96 weeks
Läkemedel: TMC278
25 mg tablett en gång dagligen i 96 veckor

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Genomsnittlig förändring från baslinje till vecka 48 och vecka 96 i absoluta och relativa CD4+-cellantal (med imputerade data)
Tidsram: Baslinje, vecka 48 och vecka 96
Förändring från baslinjen i CD4+-cellantal tillräknades i händelse av saknade värden: vid för tidig utsättning tillräknades data med baslinjevärdet efter avbrytande (dvs. change=0, Non-Completer [NC] = Failure); annars tillämpades den senaste observationen som överfördes.
Baslinje, vecka 48 och vecka 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48
Tidsram: 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
Tidsram: Week 96
Week 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96
Tidsram: Week 96
Week 96
Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96).
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 juni 2008

Primärt slutförande (Faktisk)

1 januari 2010

Avslutad studie (Faktisk)

1 februari 2012

Studieregistreringsdatum

Först inskickad

11 oktober 2007

Först inskickad som uppfyllde QC-kriterierna

11 oktober 2007

Första postat (Uppskatta)

15 oktober 2007

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

1 april 2016

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 mars 2016

Senast verifierad

1 mars 2016

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CR002704
  • TMC278-TIDP6-C215 (Annan identifierare: Tibotec Pharmaceuticals, Ireland)

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