Clinical trial NCT00543725: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
HIV-1
Keywords: Antiretroviral
HIV-1
AIDS
TMC278-C215
TMC278-TiDP6-C215
Treatment Naive
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2007-10-15
Enrollment: 680
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 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.

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.

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 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

Primary outcomes:
measure: Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 Per mL) at Week 96
timeFrame: Week 96
measure: Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 18 months for TMC278 and 12 months for Efavirenz
measure: Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per 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 Per 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 Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
timeFrame: Week 96
Other outcomes:
Locations:
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Atlantis
country: United States
state: Florida
city: Miami Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Lexington
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Newark
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Flushing
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Longview
country: United States
state: Texas
city: Darlinghurst
country: Australia
city: Prahran
country: Australia
city: Surry Hills
country: Australia
city: Antwerpen
country: Belgium
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Campinas
country: Brazil
city: Distrito Barao Geraldo-Campina
country: Brazil
city: Pinheiros
country: Brazil
city: Recife
country: Brazil
city: Sao Paulo
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Providencia
country: Chile
city: Santiago
country: Chile
city: Beijing
country: China
city: Guangzhou
country: China
city: Shanghai
country: China
city: San Jose
country: Costa Rica
city: Clamart
country: France
city: Le Kremlin Bicetre
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Köln
country: Germany
city: Mannheim
country: Germany
city: Chennai
country: India
city: Nagpur
country: India
city: Guadalajara N/A
country: Mexico
city: Mexico City
country: Mexico
city: Panama City N/A
country: Panama
city: Panama
country: Panama
city: Porto
country: Portugal
city: San Juan
country: Puerto Rico
city: Moscow N/A
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Dundee
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria N/A
country: South Africa
city: Westdene Johannesburg Gauteng
country: South Africa
city: Barcelona N/A
country: Spain
city: Barcelona
country: Spain
city: Elche
country: Spain
city: Madrid
country: Spain
city: Bangkok
country: Thailand
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland 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: 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.