Clinical trial NCT01102972: A Simplification Study of Unboosted Reyataz With Epzicom (ASSURE)
Official title: 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 to ATV + Abacavir/Lamivudine Without RTV in Virologically Suppressed, HIV-1 Infected, HLA-B*5701 Negative Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infection, Human Immunodeficiency Virus
Keywords: HIV-1
HIV
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2010-04-13
Enrollment: 297
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c)/Milliliter (mL) at the Week 24 Visit: TLOVR Analysis
timeFrame: Week 24
Secondary outcomes:
measure: 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
timeFrame: Week 24
measure: 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
timeFrame: Week 48
measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: TLOVR Analysis
timeFrame: Week 24
measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: TLOVR Analysis
timeFrame: Week 48
measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: Observed, MD=F, and SNAPSHOT Analyses
timeFrame: Week 24
measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: Observed, MD=F, and SNAPSHOT Analyses
timeFrame: Week 48
measure: Change From Baseline in HIV-1 RNA at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in HIV-1 RNA at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Cholesterol/HDL Ratio at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in Cholesterol/HDL Ratio at Week 48
timeFrame: Baseline and Week 48
measure: Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 24
timeFrame: From Baseline to Week 24
measure: Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 48
timeFrame: From Baseline to Week 48
measure: Number of Participants Who Experienced Death and/or Disease Progression
timeFrame: From Baseline to Week 48
measure: Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 24
timeFrame: From Baseline to Week 24
measure: Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 48
timeFrame: From Baseline to Week 48
measure: Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 24 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir
timeFrame: From Baseline to Week 24
measure: Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 48 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir
timeFrame: From Baseline to Week 48
measure: Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group
timeFrame: From Baseline to Week 24
measure: Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group
timeFrame: From Baseline to Week 48
Other outcomes:
Locations:
city: Hobson City
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Beverly Hills
country: United States
facility: GSK Investigational Site
state: California
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Daytona Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Wilton Manor
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Boise
country: United States
facility: GSK Investigational Site
state: Idaho
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Berkeley
country: United States
facility: GSK Investigational Site
state: Michigan
city: East Lansing
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Hillsborough
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Valhalla
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Ponce
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Robertson K, Maruff P, Wohl D, et al. Similar cognition outcomes after 24 weeks for tenofovir/FTC + atazanavir/r (ATV/r)-experienced HIV+ subjects or subjects simplifying to abacavir/3TC+ATV. Published at: Conference on Retroviruses and Opportunistic Infections - 20th Annual; March 3-6, 2013; Atlanta, GA.
citation: D. Wohl, L. Bhatti, P. Maruff, K. Robertson, C. Small, H. Edelstein, H. Zhao, D. Margolis, L. Ross, M. Shaefer, on behalf of the ASSURE (EPZ113734) Study Team. Prevalence of HIV Associated Neurocognitive Disorders (HAND) in Virologically Suppressed HIV+ Individuals. 19th International AIDS Conference; July 22-27, 2012; Washington, DC. Poster WEPE092.
citation: C. B. Small, D. Wohl, D. A. Margolis, B. Wine, L. L. Ross, H. Zhao, and M. S. Shaefer. Prevalence of HLA-B*5701 Allele in HIV-infected Subjects in North America and Reductions in Risk for Development of Abacavir Associated Hypersensitivity Reaction (ABC HSR). 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 9-12, 2012; San Francisco, CA. Poster H-895
citation: D. Wohl, L. Bhatti, C. B. Small, H. Edelstein, H. Zhao, D. A. Margolis, L. L. Ross, M.S. Shaefer. Simplification to Abacavir/Lamivudine (ABC/3TC) + Atazanavir (ATV) from Tenofovir/Emtricitabine (TDF/FTC) + ATV/Ritonavir (RTV, /r) Maintains Viral Suppression and Improves Bone Biomarkers. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 9-12, 2012; San Francisco, CA. Oral presentation H-556c.
citation: Small CB, Margolis DA, Shaefer MS, Ross LL. HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects. BMC Infect Dis. 2017 Apr 11;17(1):256. doi: 10.1186/s12879-017-2331-y.
citation: Wohl DA, Bhatti L, Small CB, Edelstein H, Zhao HH, Margolis DA, DeJesus E, Weinberg WG, Ross LL, Shaefer MS. Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial. PLoS One. 2014 May 13;9(5):e96187. doi: 10.1371/journal.pone.0096187. eCollection 2014.