Purpose / Objectives

Primary Outcome

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 Outcomes

To evaluate the efficacy, safety and tolerability of the two
treatment arms through 48 weeks of treatment

Diagnosis

• HIV-1
• Infectiology/HIV and AIDS

Antiretroviral treatment-experienced, HIV-1 infected adults with
plasma HIV-1 RNA levels ≥ 1,000 copies/mL

Target population

Age

18-99

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 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), 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.
ü 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.
ü 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 of birth control (as described above) to participate in the study.
ü Male subjects who are sexually active must be willing to use effective barrier
contraception (e.g., condom with spermicide) during heterosexual intercourse fromAdequate 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.
ü 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.
ü 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 of birth control (as described above) to participate in the study.
ü Malscreening through completion of the study and continue for at least 30 days from date
of last dose of study drug.
• Age ≥ 18 years.
• Life expectancy ≥ 1 year.
• The ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures.e subjects who are sexually active must be willing to use effective barrier
contraception (e.g., condom with spermicide) during heterosexual intercourse from

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)
• 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 below that is not to be
taken with a component of the BR, including drugs not to be used with ritonavir (refer to
prescribing information); examples include the following

Study design

• Phase III
• Multicenter
• Prospective
• Two-arm
• Double-blind
• Randomized
• Placebo-controlled

Intervention

Treatment Arm 1: Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir
85 mg QD for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR (N = 350)
Treatment Arm 2: Raltegravir 400 mg BID + BR (N = 350)
Randomization will be stratified by screening HIV-1 RNA level (≤ 100,000 copies/mL or
> 100,000 copies/mL) and the class of the second single agent (NRTI versus other classes).

Documents (password protected)

Go to download area

Responsibilities in overall study

Sponsor

Gilead Sciences, Inc.

(National) Coordinating Investigator

Dr. med. Albrecht Stoehr

Monitoring

Parexel International GmbH

• Tel. +49 30 30 685 0
• Fax +49 30 30 685 299