Treatment Simplification by Darunavir/Ritonavir 800/100 mg Once a Day Versus a Triple Combination Therapy With Darunavir/Ritonavir

Condition(s) targeted: AIDS Virus; Acquired Immunodeficiency Syndrome Virus; HIV Infections; Human Immunodeficiency Virus

Intervention: darunavir (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Janssen-Cilag International NV

Official(s) and/or principal investigator(s):
Janssen-Cilag International NV Clinical Trial, Study Director, Affiliation: Janssen-Cilag International NV

Overall contact:
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: info1@veritasmedicine.com

The purpose of the study is to compare the efficacy, safety and tolerability of darunavir/ritonavir 800/100 mg once a day (O. D.) as a monotherapy versus a triple combination therapy containing 2 nucleosides and darunavir/ritonavir in 250 HIV-1 infected patients who have been on Highly Active Antiretroviral Therapy (HAART) and have plasma viral load below 50 copies/ml for at least 24 weeks.

Official title: A Randomised, Controlled, Open-Label Trial to Compare the Efficacy, Safety and Tolerability of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg O.D. vs a Triple Combination Therapy With DRV/r in HIV-1 Infected Patients With Undetectable Plasma HIV-RNA on Their Current Treatments.

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Percentage of patients with a plasma viral load < 50 copies/mL at Week 48 by intent to treat (ITT) analyses.

Secondary outcome: To compare CD4-cell count, list of mutations, lipids, and resolution of toxicities at baseline and over 48 weeks of therapy in both treatment groups.

Detailed description: This study is randomised (patients are assigned different treatments based on chance), controlled, open-label trial to compare the efficacy, safety and tolerability of darunavir/ritonavir (DRV/r) 800/100 mg once a day (O. D.) as a monotherapy versus a triple combination therapy containing 2 nucleosides and DRV/r in 250 HIV-1 infected patients. Patients will be considered eligible if they have not changed any antiretroviral drugs for at least 8 weeks prior to screening and have documented evidence of plasma viral load (or plasma HIV-1 RNA) < 50 copies/mL for at least 24 weeks prior to being screened. The trial will consist of a screening period up to 4 weeks, a 48-week treatment period, followed by a 4-week follow-up (FU) period. The primary objective is to demonstrate non-inferiority in efficacy of DRV/r versus the triple combination therapy containing DRV/r, with respect to confirmed virologic response, defined as plasma HIV-1 RNA < 50 copies/mL at 48 weeks. Patients will be assigned a study medication based on a 1: 1 ratio to either switch to a triple combination therapy containing 2 nucleosides and DRV/r 800/100 mg O. D, or initiate monotherapy with DRV/r 800/100 mg O. D. Patients in the triple combination arm who are already on 2 nucleosides prior to randomisation may remain on these or switch them at baseline. Patients randomised to the monotherapy arm will discontinue Highly Active Antiretroviral Therapy (HAART) at baseline and commence DRV/r 800/100 mg O. D. A Data and Safety Monitoring Board (DSMB) has been commissioned for this study. The role of the DSMB is to review the progress of the trial and the accumulating data to detect evidence of early safety issues for the patients while the trial is ongoing. An interim analysis will be performed after 24 weeks of treatment. The results of the Week 24 analysis will be used to determine whether long-term follow-up to 72 and 96 weeks will be done. The protease inhibitor (PI) component of the regimen cannot be changed until the end of the treatment period and the nucleoside reverse transcriptase inhibitors (NRTIs) cannot be modified until the end of the treatment period with the following exception: single antiretroviral (ARV) substitutions will be allowed for tolerability/toxicity reasons, as long as this can be linked to an adverse event (AE) or an serious adverse event (SAE). After withdrawal of the patient from the trial, changes in the ARV regimen are allowed after the assessments of the withdrawal visit have been performed. Temporary interruption of all ARVs will be allowed in the event of suspected toxicity, as long as the temporary interruption is associated with and can be linked to an AE or a SAE. For the control arm, the nucleoside analogues could be re-optimized at baseline or on study, and all approved ARVs allowed. However, PIs other than DRV/r are not allowed during the treatment period. Patients who cannot resume study medication will have to be withdrawn. A physical examination will be done at protocol-scheduled visits and vital signs will be monitored at each study visit. In addition, at each study visit, every patient will be asked about the occurrence of or change to AEs since they were last seen by the investigator. Laboratory samples for haematology and serum chemistry will be drawn and the results determined and transmitted to the investigator. Urinalysis will be performed. Pregnancy test will be done at each visit for female participants of child-bearing potential. The primary endpoint will be the proportion with virologic response, defined as a confirmed plasma HIV-1 RNA < 50 copies/mL at Week 48. The study hypothesis is that DRV/r monotherapy will be as effective as a triple combination regimen and will be well tolerated in this early pre-treated HIV-1 patients.

Two 400mg tablets of darunavir once daily orally within 30 minutes after completion of a meal for 48 weeks.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients with documented HIV-1 infection

- Patients currently receiving HAART for at least 24 weeks

- Plasma viral load < 50 copies/mL for at least 24 weeks prior to screening (two results

must be documented)

- Patients taking the same antiretroviral combination for at least 8 weeks before

screening

- Patients and physician's preference to change the current HAART regimen for reasons of

simplification and/or toxicity

- CD4 > 100/mm3 at the start of HAART and > 200/mm3 at screening

Exclusion Criteria:

- No history of virological failure defined as two consecutive plasma HIV-1 RNA > 500

copies/mL while on previous or current antiretroviral therapy

- No history of any primary PI mutations as defined by the IAS-USA guidelines 2006

- No patients co-infected with hepatitis B

- No pregnant or breastfeeding women

- No active clinically significant disease or life threatening 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

Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: info1@veritasmedicine.com

Wien, Austria; Active, not recruiting

Wien 1090, Austria; Active, not recruiting

Antwerpen, Belgium; Recruiting

Bruxelles, Belgium; Active, not recruiting

Copenhagen, Denmark; Active, not recruiting

Aarhus, Denmark; Recruiting

Odense, Denmark; Active, not recruiting

Hvidovre 2650, Denmark; Recruiting

Hannover, Germany; Active, not recruiting

Hamburg, Germany; Active, not recruiting

Frankfurt, Germany; Active, not recruiting

Berlin, Germany; Active, not recruiting

Kÿln N/A 50924, Germany; Active, not recruiting

Budapest 1097, Hungary; Active, not recruiting

Jerusalem, Israel; Active, not recruiting

Warszawa, Poland; Active, not recruiting

Lisbon, Portugal; Active, not recruiting

Porto 4200319, Portugal; Active, not recruiting

Moscow 105275, Russian Federation; Active, not recruiting

Saint-Petersburg, Russian Federation; Active, not recruiting

Granada, Spain; Active, not recruiting

Barcelona 08036, Spain; Active, not recruiting

Valladolid N/A 47011, Spain; Active, not recruiting

Madrid 28040, Spain; Active, not recruiting

Madrid, Spain; Active, not recruiting

Badalona, Spain; Active, not recruiting

Donostia Guipuzcoa 20014, Spain; Active, not recruiting

St Gallen 9007, Switzerland; Active, not recruiting

London, United Kingdom; Active, not recruiting

London SE1 7EH, United Kingdom; Active, not recruiting

London SW10 9NH, United Kingdom; Active, not recruiting

To learn how to participate in this trial please click here.

Starting date: March 2007
Last updated: July 31, 2008