A Simplification Study of Unboosted Reyataz With Epzicom (ASSURE)

NCT ID: NCT01102972

Last Updated: 2013-11-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

297 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Study Completion Date

2012-12-31

Brief Summary

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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

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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.

Conditions

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Infection, Human Immunodeficiency Virus

Keywords

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HIV-1 HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ATV + ABC/3TC

Subjects will change to ATV 400mg administered as two 200mg capsules orally, once daily and to the fixed-dose combination tablet of ABC 600mg/3TC 300mg (EPZICOM) administered as one tablet orally, once daily for 48 weeks. The subject's pre-study RTV will be discontinued.

Group Type EXPERIMENTAL

Reyataz + Epzicom

Intervention Type DRUG

atazanavir 400mg + abacavir 600mg/lamivudine 300mg

ATV + RTV + TDF/FTC

Subjects will continue their pre-study therapy, un-modified, of ATV 300mg administered as one capsule orally, once daily plus RTV 100mg administered orally, once daily plus fixed dose combination tablet tenofovir 300mg/emtricitabine 200mg administered as one tablet orally, once daily for 48 weeks.

Group Type ACTIVE_COMPARATOR

Reyataz + Norvir + Truvada

Intervention Type DRUG

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

Interventions

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Reyataz + Norvir + Truvada

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

Intervention Type DRUG

Reyataz + Epzicom

atazanavir 400mg + abacavir 600mg/lamivudine 300mg

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

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GSK Investigational Site

Hobson City, Alabama, United States

Site Status

GSK Investigational Site

Phoenix, Arizona, United States

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GSK Investigational Site

Phoenix, Arizona, United States

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Bakersfield, California, United States

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Beverly Hills, California, United States

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Fountain Valley, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Newport Beach, California, United States

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Oakland, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Denver, Colorado, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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GSK Investigational Site

Washington D.C., District of Columbia, United States

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Daytona Beach, Florida, United States

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Fort Lauderdale, Florida, United States

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Ft. Pierce, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Beach, Florida, United States

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Orlando, Florida, United States

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West Palm Beach, Florida, United States

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Wilton Manors, Florida, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Savannah, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Berkeley, Michigan, United States

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East Lansing, Michigan, United States

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Minneapolis, Minnesota, United States

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GSK Investigational Site

Kansas City, Missouri, United States

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Hillsborough, New Jersey, United States

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Newark, New Jersey, United States

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Valhalla, New York, United States

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Chapel Hill, North Carolina, United States

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GSK Investigational Site

Charlotte, North Carolina, United States

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GSK Investigational Site

Memphis, Tennessee, United States

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Dallas, Texas, United States

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GSK Investigational Site

Houston, Texas, United States

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GSK Investigational Site

Lynchburg, Virginia, United States

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GSK Investigational Site

Spokane, Washington, United States

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GSK Investigational Site

Ponce, Puerto Rico, Puerto Rico

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GSK Investigational Site

San Juan, Puerto Rico, Puerto Rico

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Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND

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.

Reference Type RESULT

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

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type DERIVED
PMID: 28399804 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24825167 (View on PubMed)

Related Links

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http://www.viivhealthcare.com

ViiV Healthcare Website

http://www.epzicom.com

Click here for more information about Epzicom

Other Identifiers

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113734

Identifier Type: -

Identifier Source: org_study_id