Clinical trial NCT00381303: 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.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Infectious
Keywords: HIV
AIDS
Immunodeficiency Virus, Human
Females
Women
PREZISTA
darunavir
TMC114
Protease Inhibitor
Lead sponsor: Tibotec, Inc
Sponsor class: INDUSTRY
Collaborators: name: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
First posted: 2006-09-27
Enrollment: 429
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate any differences in the effectiveness, safety, and tolerability of PREZISTA (darunavir; DRV) 600 mg, administered with ritonavir (RTV) 100 mg twice a day on virologic response (defined as a viral load (VL) of \< 50 copies/mL) over a 48-week treatment period in HIV-positive women and men. Additional antiretroviral (ARV) 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)).

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 (VL) 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 (TLOVR), 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.

Eligibility criteria: Inclusion Criteria:

* Documented HIV infection
* Plasma HIV-RNA \>= 1000 copies/mL
* 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).

Primary outcomes:
measure: Number of Viral Load (VL) < 50 HIV-1 RNA Copies/mL (Time to Loss of Virologic Response[TLOVR]) Subjects by Sex
timeFrame: Week 48
measure: Number of TLOVR Non-virologic Failure (VF) Censored - VL < 50 HIV-1 RNA Subjects by Sex
timeFrame: Week 48
Secondary outcomes:
measure: Number of VL < 50 HIV-1 RNA Copies/mL (TLOVR) Subjects by Race
timeFrame: Week 48
measure: Number of Etravirine-TMC125 (ETR) Subgroup- VL < 50 HIV-1 RNA Copies/mL (TLOVR) Subjects
timeFrame: Week 48
measure: Descriptive Statistics of [TLOVR Non-virologic Failure (VF) Censored] - VL < 50 HIV-1 RNA by Race
timeFrame: Week 48
measure: Descriptive Statistics of ETR Subgroup [TLOVR Non-virologic Failure (VF) Censored] - VL < 50 HIV-1 RNA
timeFrame: Week 48
measure: Descriptive Statistics of Change From Baseline in CD4+ Cell Count Using Observed Values
timeFrame: Baseline, Week 48
measure: Descriptive Statistics of ETR Subgroup - Change From Baseline in CD4+ Cell Using Observed Values
timeFrame: Week 48
measure: Descriptive Statistics of Change From Baseline in CD4+ Cell Count Using the Imputation Method of Last Observation Carried Forward (LOCF)
timeFrame: Week 48
measure: Descriptive Statistics of ETR Subgroup - Change From Baseline in CD4+ Cell Count Using the Imputation Method of LOCF
timeFrame: Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Torrance
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Fort Lauderdale
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: North Palm Beach
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Port St Lucie
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Neptune
country: United States
state: New Jersey
city: Newark
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Harlingen
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Longview
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Ponce
country: Puerto Rico
city: Rio Piedras
country: Puerto Rico
Study officials:
affiliation: Tibotec, Inc
name: Tibotec, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Tsoukas C, Gilbert L, Lewis T, Hatzakis G, Falcon R, Mrus J. Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy. ISRN AIDS. 2013 Dec 12;2013:358294. doi: 10.1155/2013/358294. eCollection 2013.
citation: Smith KY, Garcia F, Kumar P, Currier JS, Ryan R, Falcon R, Mrus J, Squires K. Assessing darunavir/ritonavir-based therapy in a racially diverse population: 48-week outcomes from GRACE. J Natl Med Assoc. 2012 Jul-Aug;104(7-8):366-76. doi: 10.1016/s0027-9684(15)30179-6.
citation: Currier J, Averitt Bridge D, Hagins D, Zorrilla CD, Feinberg J, Ryan R, Falcon R, Tennenberg A, Mrus J, Squires K; GRACE (Gender, Race, And Clinical Experience) Study Group. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med. 2010 Sep 21;153(6):349-57. doi: 10.7326/0003-4819-153-6-201009210-00002.