Clinical trial NCT00540449: TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
HIV-1
Human Immunodeficiency Virus Type 1
Keywords: TMC278-C209
Antiretroviral
Non-nucleoside reverse transcriptase inhibitor
HIV-1
AIDS
TMC278-TiDP6-C209
Treatment Naive
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2007-10-08
Enrollment: 694
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

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.

Eligibility criteria: 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 TDF and FTC
* Patient agrees not to start ART (antiretroviral treatment) before the baseline visit

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

Primary outcomes:
measure: Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48
timeFrame: Week 48
measure: Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96
timeFrame: Week 96
measure: The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96
timeFrame: Week 96
measure: Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96).
timeFrame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit
measure: Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48
timeFrame: Week 48
measure: Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96
timeFrame: Week 96
measure: Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data)
timeFrame: Baseline, Week 48, and Week 96
measure: Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure
timeFrame: Week 96
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Fort Lauderdale
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Macon
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Newark
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Guernica
country: Argentina
city: Darlinghurst
country: Australia
city: Melbourne
country: Australia
city: Perth
country: Australia
city: Surry Hills
country: Australia
city: Innsbruck
country: Austria
city: Vienna
country: Austria
city: Wien
country: Austria
city: Curitiba
country: Brazil
city: Nova Iguacu
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Copenhagen
country: Denmark
city: Hvidovre N/A
country: Denmark
city: Odense N/A
country: Denmark
city: Loire
country: France
city: Lyon
country: France
city: Paris Cedex 10
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Tourcoing
country: France
city: Villejuif Cedex
country: France
city: Ciudad De Mexico
country: Mexico
city: Zapopan
country: Mexico
city: Rotterdam
country: Netherlands
city: Amadora
country: Portugal
city: Lisboa
country: Portugal
city: Portimao
country: Portugal
city: Porto
country: Portugal
city: San Juan
country: Puerto Rico
city: Bucuresti
country: Romania
city: Iasi
country: Romania
city: Timisoara
country: Romania
city: Krasnodar
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Durban N/A
country: South Africa
city: Houghton, Johannesburg
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria N/A
country: South Africa
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Kaohsiung County
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Birmingham
country: United Kingdom
city: Brighton
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.