Human Innunodeficiency Virus (HIV-1) Infections MedDRA version: 15.0 Level: LLT Classification code 10020192 Term: HIV-1 System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Gilead Sciences Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Exemptions for inclusion and exclusion criteria will not be granted. Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: • Plasma HIV-1 RNA levels = 1,000 copies/mL at screening. • Subjects must have documented resistance, as defined by current IAS-USA definitions (refer to Appendix 5 of the protocol), or at least six months experience prior to screening with two or more different classes of antiretroviral agents. Thus, subjects may have resistance to one class and at least six months experience prior to screening with a second class of antiretroviral agents, or resistance to two classes of antiretroviral agents, or at least six months experience with the two classes of antiretroviral agents. Subjects may also have resistance or at least six months experience prior to screening with three or more classes of antiretroviral agents. • Stable antiretroviral regimen for at least 30 days prior to screening; however, subjects may discontinue the antiretroviral regimen after screening and remain off therapy until baseline at the discretion of the investigator. • Subjects must be eligible to receive one of the fully-active ritonavir-boosted-PIs, based on the results of screening phenotype analysis provided by Monogram Biosciences, and an allowed second agent (see Table 3-1). Fully-active PIs are defined as those with fold changes below the lower clinical or biological cutoff for each drug. • Normal ECG (or if abnormal, determined by the investigator to be not clinically significant). • Adequate renal function: Estimated glomerular filtration rate = 60 mL/min according to the Cockcroft-Gault formula: Male: (140 – age in years) × (wt in kg) = CLcr (mL/min)/ 72 × (serum creatinine in mg/dL) Female: (140 – age in years) × (wt in kg) × 0.85 = CLcr (mL/min)/ 72 × (serum creatinine in mg/dL) • Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN). • Total bilirubin = 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert’s Syndrome or hyperbilirubinemia due to indinavir or atazanavir therapy may have total bilirubin up to 5 × ULN). • Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets = 50,000/mm3; hemoglobin = 8.5 g/dL). • Serum amylase 40 mIU/mL. If the FSH is = 40 mIU/mL, the subject must agree to use highly effective method of birth control
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in (or may be discontinued from) this study: • A new AIDS-defining condition diagnosed within the 30 days prior to screening (Refer to Appendix 6 of the protocol) • Prior treatment with any HIV-1 integrase inhibitor • Subjects experiencing ascites • Subjects experiencing encephalopathy • Females who are breastfeeding • Positive serum pregnancy test at any time during the study (female of childbearing potential) • Subjects receiving ongoing therapy with any medication listed in section 4.3. of the protocol that is not to be taken with a component of the BR, including drugs not to be used with ritonavir (refer to prescribing information). Administration of any of the medications detailed in section 4.3. of the protocol must be discontinued at least 30 days prior to the Baseline/Day 1 visit and for the duration of the study. • Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance. • A history of or ongoing malignancy other than cutaneous Kaposi’s sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and are not anticipated to require systemic therapy during the study. • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline. • Participation in any other clinical trial (except for the Etravirine or Maraviroc expanded access programs), without prior approval from the sponsor, is prohibited while participating in this trial. • Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements. • Known hypersensitivity to the study drugs, the metabolites or formulation excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess non-inferiority of a regimen containing ritonavirboosted elvitegravir versus raltegravir, each administered with a background regimen in HIV-1 infected, antiretroviral treatment-experienced adult subjects as determined by the proportion of subjects achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL through Week 48;Secondary Objective: To evaluate the efficacy, safety and tolerability of the two treatment regimens through 96 weeks of treatment To evaluate the long-term safety, tolerability, and efficacy of elvitegravir administered with a background regimen;Primary end point(s): The primary efficacy endpoint is the proportion of subjects achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL through Week 48.;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Virologic response at Weeks 48 and 96 (HIV-1 RNA < 50 copies/mL, snapshot analysis) • The proportion of subjects achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL through Week 96 • The proportion of subjects achieving and maintaining confirmed HIV-1 RNA < 400 copies/mL through Weeks 48 and 96 • The time to pure virologic failure for HIV-1 RNA cutoff at 50 copies/mL up to Weeks 48 and 96 • The time to pure virologic failure for HIV-1 RNA cutoff at 400 copies/mL up to Weeks 48 and 96 • The proportion of subjects with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 • The proportion of subjects with HIV-1 RNA < 400 copies/mL at Weeks 48 and 96 • The change from baseline in log10 HIV-1 RNA (copies/mL) at Weeks 48 and 96 • The change from baseline in CD4+ cell count at Weeks 48 and 96;Timepoint(s) of evaluation of this end point: Week 48 Week 96 | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Mexico, Netherlands, Portugal, Puerto Rico, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd
Outcome results
None listed