A Simplification Study of Unboosted Reyataz With Epzicom (ASSURE)

ViiV Healthcare297 enrolled

Overview

This study is designed to compare the efficacy and safety of simplifying therapy from a regimen of atazanavir (ATV) + ritonavir (RTV) + tenofovir/emtricitabine (TDF/FTC) to a regimen of ATV + abacavir sulfate/lamivudine (ABC/3TC) without RTV in virologically suppressed, HIV-1 infected, HLA-B\*5701 negative subjects for 48 weeks.

A prospective, randomized, multicenter, open-label study to compare the efficacy and safety of simplifying from a regimen of atazanavir (ATV) + ritonavir (RTV) + tenofovir/emtricitabine (TDF/FTC) to ATV + abacavir sulfate/lamivudine (ABC/3TC) without RTV for 48 weeks in virologically suppressed, HIV-1 infected, HLA-B\*5701 negative subjects. ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

297

Conditions

Infection, Human Immunodeficiency Virus

Interventions

Reyataz + Norvir + TruvadaDRUG

atazanavir 300mg + ritonavir 100mg + tenofovir 300mg/emtricitabine 200mg

Reyataz + EpzicomDRUG

atazanavir 400mg + abacavir 600mg/lamivudine 300mg

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subject is an adult (greater than or equal to 18 years) with documented HIV-1 infection * Subject is a male or female of non-childbearing potential (physiologically incapable of becoming pregnant, is pre-menarchal or post-menopausal) or child-bearing potential with a negative pregnancy test who agrees to avoid pregnancy by sexual abstinence or utilization of a highly effective method of birth control throughout the study period * Subject is receiving a once-daily regimen of ATV (300mg) + RTV (100mg) + TDF/FTC (300mg/200mg) for at least 6 months prior to or by the first day of screening. ATV + RTV + TDF/FTC must be the subejct's INITIAL regimen or FIRST or SECOND SWITCH regimen. If ATV + RTV + TDF/FTC is subject's first or second switch regimen, then subject may ONLY have received the following prior regimens: a) any currently licensed non-nucleoside reverse transcriptase inhibitor (NNRTI) + TDF/FTC or ZDV/3TC; b) RTV-boosted PI with TDF/FTC or ZDV/3TC; or c) an alternative regimen not listed above after approval by Sponsor. * Subject is virologically suppressed on ATV + RTV + TDF/FTC defined as HIV-1 RNA \</=75 copies/mL at 2 consecutive timepoints, one of which is at Screening and the other at least 28 days prior to Screening Exclusion Criteria: * Subject has evidence of virologic failure * Subject has any known HIV genotyping results indicating HIV virus contains any of the following resistance mutations in reverse transcriptase including K65R, K70E, L74V, M184I/V or Y115F, a combination of two or more thymidine analog mutations including M41L, D67N, K70R, K219Q or E that include changes at either L210 or T215), or 3 or more of the following HIV-1 protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90 * Subject is HLA-B\*5701 positive * Subject has hypersensitivity to any component of the study drugs * SUbject is pregnant or breastfeeding * Subject is enrolled in one or more investigational drug protocols within 30 days of screening * Subject has an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial * Subject has ongoing clinically relevant hepatitis at screening and/or positive for Hepatitis B (+ HbsAg) * Subject has a creatinine clearance \<50 mL/min via the Cockcroft-Gault method * Subject has a verified Grade 4 laboratory abnormality at screening unless the Investigator can provide a compelling explanation (e.g. elevated CPK due to exercise) for the laboratory result(s) and has the assent of the Sponsor * Subject has any other laboratory abnormality or medical condition at screening, which, in the opinion of the investigator, would preclude the subject's participation in the study * Subject has had an immunization within 30 days prior to first dose of investigational product * Subject has had any exposure to treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, or interferons) or receipt of an HIV-1 immunotherapeutic vaccine within 90 days prior to screening. Subjects using inhaled corticosteroids or short-course systemic corticosteroids (less than or equal to 14 days) are eligible for enrollment. * Subject has had treatment with radiation therapy or cytotoxic chemotherapeutic agents within 90 days prior to screening, or has an anticipated need for these agents within the study period * Subject has had treatment within 30 days prior to first dose of investigational product for or an anticipated need during the study of any medications which can have interactions with the study medications, TDF, FTC, ABC, 3TC, ATV and/or RTV, as described in current product labelling * Subject has had treatment with any previous abacavir-containing regimen

Locations (46)

Outcomes

Primary Outcomes

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c)/Milliliter (mL) at the Week 24 Visit: TLOVR Analysis

The percentage of PAR with HIV-1 RNA virus \<50 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load \<50 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA \<50 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/mL, or had an unconfirmed HIV RNA of at least 50 c/mL at the last visit.

Time frame: Week 24

Secondary Outcomes

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 24 Visit: Observed, M/D=F, and SNAPSHOT Analyses

The percentage of PAR with HIV-1 RNA virus \<50 c/mL determined from blood samples drawn through Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.

Time frame: Week 24

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 48 Visit: TLOVR, Observed, M/D=F, and SNAPSHOT Analyses

The percentage of PAR with HIV-1 RNA virus \<50 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.

Time frame: Week 48

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: TLOVR Analysis

The percentage of PAR with HIV-1 RNA virus \<400 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load \<400 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA \<400 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 400 c/mL, or had an unconfirmed HIV RNA of at least 400 c/mL at the last visit.

Data from ClinicalTrials.gov

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GSK Investigational Site

Hobson City, Alabama, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Bakersfield, California, United States

GSK Investigational Site

Beverly Hills, California, United States

GSK Investigational Site

Fountain Valley, California, United States

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Newport Beach, California, United States

GSK Investigational Site

Oakland, California, United States

...and 36 more locations

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: TLOVR Analysis

The percentage of PAR with HIV-1 RNA virus \<400 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load \<400 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA \<400 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 400 c/mL, or had an unconfirmed HIV RNA of at least 400 c/mL at the last visit.

Time frame: Week 48

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: Observed, MD=F, and SNAPSHOT Analyses

Time frame: Week 24

Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: Observed, MD=F, and SNAPSHOT Analyses

Time frame: Week 48

Change From Baseline in HIV-1 RNA at Week 24

Change from Baseline was calculated as the Week 24 value minus the Baseline value. Blood was drawn to analyze for plasma HIV viral load.

Time frame: Baseline and Week 24

Change From Baseline in HIV-1 RNA at Week 48

Change from Baseline was calculated as the Week 48 value minus the Baseline value. Blood was drawn to analyze for plasma HIV viral load.

Time frame: Baseline and Week 48

Change From Baseline in CD4+ Cell Count at Week 24

Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from Baseline was calculated as the Week 24 value minus the Baseline value.

Time frame: Baseline and Week 24

Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline and Week 48

Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 24

Triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured at Week 24. A Fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 24 value minus the Baseline value for each parameter.

Time frame: Baseline and Week 24

Change From Baseline in Cholesterol/HDL Ratio at Week 24

A Fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 24 value minus the Baseline value.

Time frame: Baseline and Week 24

Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 48

Triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured or calculated at Week 48. A fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 48 value minus the Baseline value for each parameter.

Time frame: Baseline and Week 48

Change From Baseline in Cholesterol/HDL Ratio at Week 48

A fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 48 value minus the Baseline value for each parameter.

Time frame: Baseline and Week 48

Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 24

The number of participants that failed to remain virologically suppressed through 24 weeks on treatment was assessed. Viral failure is defined per protocol as confirmed HIV-1 RNA \>=400 c/mL.

Time frame: From Baseline to Week 24

Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 48

The number of participants that failed to remain virologically suppressed from baseline through 48 weeks on treatment was assessed. Viral failure is defined per protocol as confirmed HIV-1 RNA \>=400 c/mL.