GRACE: New HIV Study Shows that Large Numbers of Women and People of Color can be Successfully Enrolled in U.S. HIV Clinical Studies
GRACE compares efficacy and safety of PREZISTA/ritonavir in treatment-experienced women vs. men at 48 weeks
from Jules: More important than enrolling women of color in studies is to provide the needed services.
[Bridgewater, NJ, July 20] - Data from a historic HIV study demonstrate that it is possible to recruit large numbers of women, African Americans and Latinos into U.S.-based HIV-1 treatment studies. The study, known as GRACE, is the largest study to date in treatment-experienced adult women with HIV-1 to examine gender and race differences in response to an HIV-1 therapy - PREZISTA« (darunavir) coadministered with ritonavir as part of combination therapy. GRACE findings were presented today at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) in Cape Town, South Africa.
In the United States, women are increasingly affected by HIV/AIDS, accounting for more than one quarter of all new HIV/AIDS diagnoses, with African American and Latina women representing 79 percent of women living with the disease. Despite the increasing numbers of women with HIV, they have been under-represented in clinical treatment studies. In recent HIV studies of treatment-experienced patients, women accounted for less than 11 percent of the patients being studied, on average. GRACE was able to enroll 67 percent women and 84 percent people of color.
The GRACE (Gender, Race And Clinical Experience) study demonstrated that through 48 weeks of therapy, there were no statistically significant differences in virologic response rates between treatment-experienced women and men receiving the protease inhibitor PREZISTA (600 mg twice daily with 100 mg ritonavir), with a background regimen. In addition, there were no clinically relevant gender-based differences in adverse events.
"GRACE not only showed us that PREZISTA/r had similar efficacy and tolerability in treatment-experienced men and women, but it also taught us that through unique recruitment and retention strategies, a large number of women and people of color can enroll and stay in HIV clinical trials," said Kathleen Squires, MD, Director, Division of Infectious Diseases, Thomas Jefferson University and primary investigator in the GRACE study. "GRACE has the potential to shape how future HIV studies should be conducted because it addressed head-on the social and economic barriers, such as lack of support, stigma, availability of child care and lack of transportation, which often have prevented women and people of color from participating in HIV clinical studies and remaining in care."
Tibotec Therapeutics Clinical Affairs, a division of Centocor Ortho Biotech Services, the sponsor of the GRACE study, assembled a group of physicians and advocates, some of whom are people living with HIV, to help design and advise on the GRACE study. The company is conducting additional research to determine from the participants' perspective which recruitment and retention strategies were most effective for them.
"GRACE sets a new standard for how future HIV studies should be conducted, as we now know that treatment-experienced women and people of color can and will successfully participate in clinical trials if the studies are designed and supported in the right way," said Dawn Averitt Bridge, Founder and Chair, The Well Project. "Tibotec truly partnered with the HIV community and we worked together to design novel strategies that overcame traditional barriers to enrollment of women and people of color, who are disproportionally affected by HIV/AIDS."
About the GRACE Study
GRACE is a multi-center, open-label phase 4 trial that compared gender differences in the efficacy, safety, and tolerability of PREZISTA tablets with 100 mg ritonavir in treatment-experienced, HIV-1-infected women and men. The trial enrolled 287 women and 142 men. The main objective of this study was to compare the percentages of women and men who achieved virologic response, defined as a viral load of <50 copies/mL at week 48. Study participants received PREZISTA (600 mg) boosted with a low dose of ritonavir (100 mg) twice a day in combination with other antiretroviral drugs for 48 weeks.
Results from an intent-to-treat time-to-loss of virological response analysis (ITT-TLOVR) showed that 51 percent of treatment-experienced HIV-1 infected women reached an undetectable viral load (<50 copies/mL) at week 48, compared with 59 percent of men, (p=not significant). When treatment discontinuations for reasons other than virologic failure were censored (non-VF censored-TLOVR), 73 percent of both women and men reached an undetectable viral load (p=not significant). There were no clinically relevant differences in safety or tolerability between women and men. In adult patients receiving a PREZISTA/r-containing regimen, the most common treatment-related adverse events (>= 2 percent) reported of at least moderate to severe intensity (>= Grade 2) were diarrhea (4.5 percent for women and 4.9 percent for men), nausea (5.2 percent for women and 2.8 percent for men), rash (2.1 percent for women and 2.8 percent for men), weight gain (1.7 percent for women 2.1 percent in men) and vomiting (1.4 percent in women and 2.1 percent in men). Discontinuation rates due to adverse events were 7.7 percent for women and 4.2 percent for men, though no specific adverse event was listed as a reason for discontinuation in more than two people. Lost to follow-up was the most common reason for discontinuation.
"We are incredibly proud to have designed and conducted the GRACE study, and couldn't have done it without the collaboration of our physician and community advisors, as well as the women and men who participated in the study," said Glenn Mattes, President of Tibotec Therapeutics. "We hope that GRACE provides a new model for HIV research, so that enrollment in future clinical studies in the U.S. will reflect current trends in HIV/AIDS cases among women and communities of color."
Tibotec will also be presenting results from a GRACE sub-study at IAS 2009, examining recovery of functional immunity. Additional sub-studies from GRACE will follow.
PREZISTA indication: Adults
PREZISTA, co-administered with ritonavir (PREZISTA/rtv), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
This indication is based on analyses of plasma HIV RNA levels and CD4+ cell counts from 2 controlled Phase 3 trials of 48 weeks duration in antiretroviral treatment-na´ve and treatment-experienced patients and 2 controlled Phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced adult patients.
In treatment-experienced adult patients, the following points should be considered when initiating therapy with PREZISTA/rtv:
* Treatment history and, when available, genotypic or phenotypic testing should guide the use of PREZISTA/rtv.
* The use of other active agents with PREZISTA/rtv is associated with a greater likelihood of treatment response.
Important Safety Information
PREZISTA does not cure HIV-1 infection or AIDS, and does not prevent passing HIV to others.
* Coadministration of PREZISTA/r is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, or simvastatin).
* Coadministration of PREZISTA/r is also contraindicated with rifampin and products containing St. John's wort (Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance.
* Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, and pravastatin.
* Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA/r. This list of potential drug interactions is not complete.
Warnings & Precautions
* PREZISTA must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer PREZISTA with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures.
* Drug-induced hepatitis (eg, acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA/r. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of patients receiving combination therapy with PREZISTA/r. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events. Post-marketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA/r therapy has not been established. Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/r and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of PREZISTA/r treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA/r should prompt consideration of interruption or discontinuation of treatment.
* Skin Rash: Cases of severe skin rashes (0.4%) and Stevens-Johnson syndrome (<0.1%) have been reported in subjects receiving PREZISTA. In clinical trials (N=3063), rash (all grades, generally mild to moderate, regardless of causality) occurred in 10.3% of subjects treated with PREZISTA. Discontinuation due to rash was 0.5%. PREZISTA should be discontinued if severe rash develops.
* Sulfa Allergy: PREZISTA should be used with caution in patients with known sulfonamide allergy.
* Diabetes Mellitus / Hyperglycemia and Hemophilia: New-onset or exacerbations of preexisting diabetes mellitus, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established.
* Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving ARV therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established.
* Immune reconstitution syndrome has been reported in patients treated with ARV therapy.
* Resistance / Cross Resistance: The potential for HIV cross-resistance among protease inhibitors has not been fully explored in PREZISTA/r-treated patients.
Use in Specific Populations
* Hepatic impairment: PREZISTA/r is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment.
* Pregnancy: PREZISTA should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women.
* In treatment-na´ve adult patients, the most common adverse drug reactions (>=2%) reported of at least moderate intensity (>=Grade 2) in the PREZISTA/r arm were diarrhea (6%), headache (5%), abdominal pain (4%), nausea (3%), vomiting (2%), and rash (2%).
* In treatment-experienced adult patients, the most common adverse drug reactions (>=2%) reported of at least moderate intensity (>=Grade 2) in the PREZISTA/r arm were diarrhea (12%), nausea (7%), rash (6%), abdominal pain (5%), vomiting (4%), asthenia (3%), headache (2%), abdominal distension (2%), and dyspepsia (2%).
This is not a complete list of all adverse drug reactions reported with the use of PREZISTA/r. Please see full Prescribing Information for more details. Full prescribing information is also available at www.PREZISTA.com.
About Tibotec Therapeutics
Tibotec Therapeutics, a division of Centocor Ortho Biotech Products, L.P., headquartered in Bridgewater, N.J., is dedicated to delivering innovative virology therapeutics that help healthcare professionals address serious unmet needs in people living with HIV.
Centocor Ortho Biotech Products, L.P. is a subsidiary of Johnson & Johnson.
Forward looking statements:
(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Tibotec Therapeutics and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2008. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither Tibotec Therapeutics nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)
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