GRACE: A Study to Compare the Effectiveness, Safety and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race When Administered With Other Antiretroviral Medications in Human Immunodeficiency Virus (HIV) Positive Women and Men.

Condition(s) targeted: HIV

Intervention: darunavir; ritonavir (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Tibotec, Inc

Official(s) and/or principal investigator(s):
Tibotec, Inc. Clinical Trial, Study Director, Affiliation: Tibotec, Inc

The purpose of this study is to evaluate any differences in the effectiveness, safety, and tolerability of PREZISTA (darunavir) 600 mg, administered with ritonavir 100 mg twice a day on virologic response (defined as a viral load of < 50 copies/mL) over a 48-week treatment period in HIV-positive women and men. Additional antiretroviral agents will also be administered and will be chosen by the Investigator based on resistance testing and prior treatment history (referred to as the Optimized Background Regimen (OBR)).

Official title: GRACE: An Open-Label, Multicenter Trial to Compare the Efficacy, Safety, and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race, When Administered in Combination With an Individually Optimized Background Regimen Over a 48-Week Treatment Period.

Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study

Primary outcome: To evaluate any differences, between women and men, in efficacy of darunavir/ritonavir (600/100 mg twice daily) plus an Optimized Background Regimen (OBR) over a 48-week treatment period.

Secondary outcome: Change in viral load and CD4 from Baseline; Safety and Tolerability; Changes in lipid profiles and metabolic parameters; Quality of Life; Assessments of body change and associated distress over the course of the 48 week study period.

Detailed description: This is a multi-center, open-label (doctors and patients know which drug is being administered), Phase IIIb clinical trial to evaluate differences in effectiveness, safety, and tolerability of darunavir/ritonavir by sex and/or race over a 48-week treatment period. This study will be conducted in HIV positive women and men who have been treated previously with antiretroviral therapy. This study will enroll 70% women and will be conducted in the U. S., Puerto Rico, Mexico and Canada in approximately 420 patients who will receive darunavir 600 mg and ritonavir 100 mg twice daily. The primary objective of this study is to determine the percentage of patients who achieve virologic response, defined as a viral load of <50 copies/mL at week 48. Secondary study objectives include comparisons of endpoints between women and men as well as race across multiple parameters including but not limited to change in CD4 count from baseline to week 48, time to loss of virologic response, changes in metabolic parameters (blood chemistry), etc. Within 4 weeks after the Screening Visit (initial visit with investigator to determine eligibility), the Investigator should have received all data required to determine the patient's eligibility and will construct the individual Optimized Background Regimen (OBR) that will be used during the treatment period in combination with darunavir/ritonavir for those patients enrolled in the study. The OBR will consist of additional antiretroviral (ARV) agents that will also be administered during the study chosen by the Investigator and based on resistance testing and prior treatment history. The study Sponsor will provide the following ARV agents, that may be used as options for the OBR: TMC 125 (investigational non-nucleoside reverse transcriptase inhibitor; NNRTI); Truvada (tenofovir/emtricitabine); Viread (tenofovir); Emtriva (emtricitabine); Zidovudine. Other NRTIs (nucleoside reverse transcriptase inhibitors) or NNRTIs may be used at the discretion of the Investigator, but will not be provided by the Sponsor. The Baseline Visit (Day 1) will be followed by a 48-week treatment period during which patients will be evaluated at Weeks 4, 8, 12, 16, 24, 36, 48 and at a final Follow-Up Visit during Week 52. (total of 10 visits from Screening to final visit). At a number of visits throughout the study, blood samples will be obtained to assess defined laboratory values, safety parameters and to determine concentrations of study drugs darunavir, TMC125 (if applicable) and ritonavir). Patients will be assessed for change in CD4 count and HIV-RNA throughout the study. At each visit, vital signs will be assessed and patients will be asked about any untoward medical occurrences and these will be recorded as adverse events (AEs) and/or HIV-related events. Detailed definitions and reporting procedures for AEs will be provided as part of the protocol.

Study patients will receive PREZISTA (darunavir) 600 mg boosted with 100 mg of ritonavir orally (by mouth) twice a day in combination with other antiretroviral drugs for 48 weeks.

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

Criteria:

Inclusion Criteria:

- Documented HIV infection

- Plasma HIV-RNA >= 1000 copies/mL

- Previous intolerance or failure to therapy consisting of a protease inhibitor (PI)

and/or NNRTI based HAART (Highly Active Antiretroviral Therapy) regimen of at least 12 weeks

- Must be able to comply with protocol requirements

Exclusion Criteria:

- No prior use of PREZISTA (darunavir), TMC125, enfuvirtide, or tipranavir

- No currently active AIDS defining illness, Category C conditions according to the

Center for Disease Control [CDC] Classification System for HIV Infection (1993) with the following exceptions, which must be discussed with the Sponsor prior to enrollment: stable cutaneous Kaposi's Sarcoma, Wasting syndrome due to HIV infection

- Not currently using an investigational drug

- Not pregnant or breastfeeding

- No Grade 3 or 4 laboratory abnormality as defined by DAIDS (Division of AIDS, National

Institute of Allergy and Infectious Diseases)

Starting date: September 2006
Ending date: November 2008
Last updated: June 12, 2008