Clinical trial NCT01422330: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Etravirine Administered in Combination With Other Antiretroviral Agents in Antiretroviral Treatment-Experienced HIV-1 Infected Patients
Official title: An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Etravirine (ETR) in Combination With Other Antiretrovirals (ARVs) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus (HIV) Infection
Keywords: Human Immunodeficiency Virus (HIV) infection
TMC125IFD3002
TMC125
Intelence
HIV
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2011-08-23
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn more about the safety and tolerability of etravirine. Etravirine is a type of non-nucleoside reverse transcriptase inhibitor (NNRTI) which has shown high activity against wild-type human immunodeficiency virus (HIV-1), and HIV strains resistant to other non-nucleotide agents.

Detailed description: This is an open-label (all people involved know the identity of the intervention), single arm, multicenter Phase IV study to evaluate the safety, tolerability, and pharmacokinetics of etravirine (ETR) in combination with antiretroviral (ARV) therapy other than darunavir (DRV) + ritonavir (rtv). In addition, the antiviral activity and the pharmacokinetic/pharmacodynamic profile, and safety of ETR will be assessed. The study will consist of a screening period of maximum 6 weeks, a baseline visit, and a 48-week treatment period. After the end of the treatment period, patients with ongoing adverse events (AEs) will be followed for an additional 4 weeks. At least 200 ARV treatment-experienced human immunodeficiency virus (HIV-1) infected patients will be enrolled in this study. Patients will be considered ARV treatment-experienced if they have been on their current stable highly active antiretroviral therapy (HAART) regimen for at least 8 weeks prior to screening. The study population will consist of patients who need to change their current HAART regimen due to any of the following reasons: (1) patients experiencing virologic failure (with a screening viral load value \>=500 HIV-1 RNA copies/mL), or (2) patients switching due to simplification of their current regimen or due to AEs and/or tolerability reasons (with a screening viral load value \<50 HIV-1 RNA copies/mL). Patients will receive ETR 200 mg twice daily in combination with an investigator-selected background regimen. In addition to ETR, which needs to be active based on resistance testing, the background regimen should consist of at least 1 active ARV resulting in a treatment regimen with at least 2 active ARVs. The following exceptions to this are: (1) if raltegravir (RAL) or atazanavir/ritonavir (ATV/rtv) are part of the background regimen, the number of active ARVs in this background regimen should be at least 2; (2) low-dose ritonavir should not be counted as an active ARV. DRV/rtv will not be allowed in the background regimen in order to evaluate the safety and pharmacokinetics of ETR in combination with ARVs other than DRV/rtv. Furthermore, a background regimen consisting of nucleoside transcriptase inhibitors (NRTIs) only will not be allowed. The background regimen cannot be modified until the end of the treatment period with the following exception: switches within the ARV class will be allowed for well documented tolerability/toxicity reasons. For patients who, in the opinion of the investigator, are deriving clinical benefit from ETR, and to whom ETR is not commercially available in his/her country, is not reimbursed or cannot be accessed from another source (e.g., access program, government program) in the region the patient is living in, the possibility to extend their ETR treatment period will be provided. The ETR tablets are to be taken orally twice daily after a meal. A total daily dose of 400 mg is to be taken for 48 weeks.

Eligibility criteria: Inclusion Criteria:

* Documented HIV-1 infection
* Treatment with current stable HAART for at least 8 weeks prior to screening
* Currently experiencing virologic failure (screening viral load value \>=500 HIV-1 RNA copies /mL), or switching due to simplification of their regimen or due to adverse event or tolerability reasons, (screening viral load value \<50 HIV-1 RNA copies /mL)
* Demonstrated sensitivity to etravirine and to at least 1 antiretroviral (ARV) agent in the background regimen, based on the resistance test at screening or resistance history or have previously received treatment with etravirine
* Patients agree not to have unprotected sex while on the study
* No currently active AIDS-defining illness
* Did not take any non-ARV investigational agents within 90 days prior to screening
* No use of disallowed treatments
* Adequate liver function

Exclusion Criteria:

* Any currently active illness or toxicity due to HIV infection
* Any active clinically significant disease or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study

Primary outcomes:
measure: Proportion of Participants with an Adverse Event (AEs)
timeFrame: 48 weeks
Secondary outcomes:
measure: Proportion of Participants with Virologic Suppression [Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) less than (<) 50 copies/Milliliter (mL)] at Week 48
timeFrame: 48 weeks
measure: Changes in CD4 Cell Count at Week 48
timeFrame: 48 weeks
measure: Changes in Viral Genotype/Phenotype Over Time
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: North Hollywood
country: United States
state: California
city: Fort Laudersale
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Springfield
country: United States
state: Massachusetts
city: Akron
country: United States
state: Ohio
city: Longview
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: Le Kremlin Bicetre
country: France
city: Paris
country: France
city: Guatemala
country: Guatemala
city: Guadalajara
country: Mexico
city: Mexico
country: Mexico
city: Iquitos
country: Peru
city: Lima
country: Peru
city: San Juan
country: Puerto Rico
city: Brasov
country: Romania
city: Constanta
country: Romania
city: Craiova
country: Romania
city: Timisoara
country: Romania
city: Krasnodar
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Sint Petersburg
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Bloemfontein
country: South Africa
city: Boksburg
country: South Africa
city: Dundee
country: South Africa
city: Durban N/A
country: South Africa
city: Johannesburg
country: South Africa
city: Newtown
country: South Africa
city: Port Elizabeth
country: South Africa
city: Pretoria N/A
country: South Africa
city: Pretoria
country: South Africa
city: Westdene Johannesburg Gauteng
country: South Africa
city: Donetsk
country: Ukraine
city: Kyiv
country: Ukraine
city: Lugansk
country: Ukraine
city: Sumy
country: Ukraine
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Arathoon E, Bhorat A, Silaghi R, Crauwels H, Lavreys L, Tambuyzer L, Vanveggel S, Opsomer M. Week 48 results of a Phase IV trial of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected treatment-experienced adults. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19783. doi: 10.7448/IAS.17.4.19783. eCollection 2014.