Clinical trial NCT00458302
Conditions: HIV Infections AIDS Virus Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome Virus
Keywords: HIV Monotherapy Darunavir Protease inhibitor Early pre-treated Undetectable Treatment Experienced
Sponsor: Janssen-Cilag International NV
Start date: 2007-06-01; Completion date: 2011-01-01
Enrollment: 256 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

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.

Arms: arm 1: darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks arm 2: darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks
Interventions: intervention 1: darunavir (DRV, TMC114) intervention 2: darunavir (DRV, TMC114)
Intervention descriptions: intervention 1: 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks intervention 2: 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks

Protocol documents: