Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL)
The purpose of this study is to compare the safety, tolerability and efficacy of a regimen containing once-daily ritonavir-boosted elvitegravir or twice-daily raltegravir added to a background regimen in HIV-1 infected, antiretroviral treatment-experienced adults who have documented resistance, or at least six months experience prior to screening with two or more different classes of antiretroviral agents.
Drug: Placebo to match elvitegravir
Drug: Placebo to match raltegravir
Drug: Background regimen
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL) Each Administered With a Background Regimen in HIV-1 Infected, Antiretroviral Treatment-Experienced Adults|
- Proportion of subjects achieving and maintaining confirmed HIV-1 RNA less than 50 copies/mL through Week 48. [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
- Proportion of subjects achieving and maintaining confirmed HIV-1 RNA less than 400 copies/mL through Week 48. [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
- Proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
- Change from baseline in log10 HIV-1 RNA (copies/mL) at Week 48 [ Time Frame: Baseline to Weeks 48 ] [ Designated as safety issue: No ]
- Change from baseline in CD4+ cell count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir 85 mg QD for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR
Elvitegravir administered orally once daily with foodDrug: Placebo to match raltegravir
Placebo to match raltegravir administered as a tablet orally twice dailyDrug: Background regimen
Background regimen (BR) administered according to prescribing information, and containing 1 fully-active ritonavir-boosted protease inhibitor (PI/r) plus 1 or 2 additional agents. Agents may include atazanavir, abacavir, darunavir, didanosine, emtricitabine, enfuvirtide, etravirine, fosamprenavir, lamivudine, lopinavir, maraviroc, tenofovir disoproxil fumarate, tipranavir, and or zidovudine
Active Comparator: Raltegravir
Raltegravir 400 mg BID + BR
Raltegravir administered orally twice daily according to the prescribing information
Other Name: IsentressDrug: Placebo to match elvitegravir
Placebo to match elvitegravir administered as a tablet orally once dailyDrug: Background regimen
This is a double-blind, double-dummy, multicenter, randomized, active-controlled study to assess the safety and efficacy of a regimen containing ritonavir-boosted elvitegravir versus raltegravir, each administered with a background regimen (BR) containing a fully-active ritonavir-boosted protease inhibitor (PI) and a second single agent in HIV-1 infected, antiretroviral treatment-experienced adults. Subjects will be randomized in a 1:1 ratio to one of the following two treatment arms:
- Treatment Arm 1: Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir 85 mg once daily (QD) for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR (N = 350)
- Treatment Arm 2: Raltegravir 400 mg BID + BR (N = 350)
Due to known pharmacokinetic interactions, subjects who are taking atazanavir/r (ATV/r) or lopinavir/r (LPV/r) as part of their BR will receive elvitegravir 85 mg if randomized to Treatment Arm 1.
The BR shall be constructed by the investigator based on viral resistance testing and shall be composed of a fully-active ritonavir-boosted PI and a second single agent.
The fully-active PI is defined by phenotypic resistance analysis. For phenotypic susceptibility, fully active is defined as being below the lower clinical or biological cutoff. The following ritonavir-boosted PIs are allowed to be prescribed by the investigator as part of the BR: atazanavir/r, darunavir/r, fosamprenavir/r, lopinavir/r, or tipranavir/r. Subjects must take their ritonavir dose based on the dosing schedule indicated in the prescribing information for the PI; no additional ritonavir is required to be taken with elvitegravir. No other marketed PIs will be allowed as part of the BR due to unknown pharmacokinetic interactions.
The second single agent may or may not be fully-active and can be one nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), etravirine, maraviroc, or T-20. However, the second single agent must not include an integrase inhibitor; the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz, nevirapine, or delavirdine (due to unknown pharmacokinetic interactions); or fixed-dose combination antiretroviral therapies.
Two identical Phase 3 studies of elvitegravir tablets boosted with ritonavir are currently ongoing in treatment-experienced adults with HIV-1 infection. Initiated in July 2008, Study GS-US-183-0144 (planned N=700) is being conducted in the US and Puerto Rico and Study GS-US-183-0145 (planned N=700) is being conducted in Europe, Australia, Mexico and Canada. Given the declining numbers of patients with unsuppressed viremia, Gilead is combining the two ongoing studies into a single, global Phase 3 study (GS-US-183-0145) to enroll a total of 700 subjects. The protocol amendment enables the transfer of subjects from Study GS-US-183-0144 into study GS-US-183-0145.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00707733
|Study Director:||Steven Chuck, MD||Gilead Sciences|