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.
- Conditions
- Human Innunodeficiency Virus (HIV-1) InfectionsMedDRA version: 9.1Level: LLTClassification code 10020192Term: HIV-1
- Registration Number
- EUCTR2007-004225-26-FR
- Lead Sponsor
- Gilead Sciences Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 724
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 using the AmpliPrep/Taqman HIV-1 Test® (with a reflex dilution for results > 10,000,000 copies/mL).
• 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 and must remain on screening regimen until the baseline visit.
• 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) = 2.5 × 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).
• Prothrombin Time = 1.25 × ULN.
• Serum amylase < 1.5 × ULN (subjects with serum amylase = 1.5 × ULN will remain
eligible if serum lipase is = 1.5 × ULN).
• Negative serum pregnancy test (females of childbearing potential only).
• Males and females of childbearing potential (i.e., a non-menopausal female or a female with menopausal = 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure; this definition includes a young woman who has not yet started menstruating) must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs.
- Female subjects who utilize hormonal contraceptive as one of their birth control
methods must have used the same method for at least three months prior to study
dosing.
- Female subjects who are postmenopausal for less than two years are required to have FSH > 40 mIU/mL. If the FSH is = 40 mIU/mL, the subject must agree to use highly effective method o
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.
• Malignancy other than cutaneous Kaposi’s sarcoma (KS) or basal cell 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 expanded access
program), 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 arms through 48 weeks of treatment;Primary end point(s): The primary efficacy endpoint is the proportion of subjects achieving and maintaining<br>confirmed HIV-1 RNA < 50 copies/mL through Week 48.
- Secondary Outcome Measures
Name Time Method