A Simplification Study of Unboosted Reyataz With Epzicom (ASSURE)

NCT01102972 | Completed Phase 4 Results

• 1 other identifier: 113734
• Study Type: interventional
• Target: 297
• Locations: 2 countries
• Sites: 46

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.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

HIV-1; HIV

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 24

Secondary Outcomes (23)

• 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

  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

  Week 48

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

  Week 24

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

  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

  Week 24

Study Arms (2)

ATV + ABC/3TC

EXPERIMENTAL

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.

Drug: Reyataz + Epzicom

ATV + RTV + TDF/FTC

ACTIVE COMPARATOR

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.

Drug: Reyataz + Norvir + Truvada

Interventions

Reyataz + Norvir + Truvada DRUG

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

ATV + RTV + TDF/FTC

Reyataz + Epzicom DRUG

atazanavir 400mg + abacavir 600mg/lamivudine 300mg

ATV + ABC/3TC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (46)

GSK Investigational Site

Hobson City, Alabama, 36201, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85012, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85015, United States

Location

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Los Angeles, California, 90069, United States

Location

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

Oakland, California, 94602, United States

Location

GSK Investigational Site

San Diego, California, 92103, United States

Location

GSK Investigational Site

San Francisco, California, 94109, United States

Location

GSK Investigational Site

Denver, Colorado, 80220, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

Location

GSK Investigational Site

Daytona Beach, Florida, 32117, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33308, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Miami, Florida, 33133, United States

Location

GSK Investigational Site

Miami, Florida, 33137, United States

Location

GSK Investigational Site

Miami Beach, Florida, 33139, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33401, United States

Location

GSK Investigational Site

Wilton Manors, Florida, 33305, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30309, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30339, United States

Location

GSK Investigational Site

Savannah, Georgia, 31401, United States

Location

GSK Investigational Site

Boise, Idaho, 83704, United States

Location

GSK Investigational Site

Chicago, Illinois, 60613, United States

Location

GSK Investigational Site

Berkeley, Michigan, 48072, United States

Location

GSK Investigational Site

East Lansing, Michigan, 48824, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55415, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64106, United States

Location

GSK Investigational Site

Hillsborough, New Jersey, 08844, United States

Location

GSK Investigational Site

Newark, New Jersey, 07102, United States

Location

GSK Investigational Site

Valhalla, New York, 10595, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38103, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Houston, Texas, 77098, United States

Location

GSK Investigational Site

Lynchburg, Virginia, 24501, United States

Location

GSK Investigational Site

Spokane, Washington, 99204, United States

Location

GSK Investigational Site

Ponce, Puerto Rico, 00717, Puerto Rico

Location

GSK Investigational Site

San Juan, Puerto Rico, 00909, Puerto Rico

Location

Related Publications (6)

• 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.

  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.

  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

  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.

  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.

  PMID: 28399804 DERIVED

• 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.

  PMID: 24825167 DERIVED

Related Links

• ViiV Healthcare Website
• Click here for more information about Epzicom

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

Atazanavir Sulfate; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; abacavir, lamivudine drug combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

This study consists of a 35-day Screening Period, a 48-week Treatment Period, and a Follow-up Period (contact \~2-4 weeks after the Week 48/Withdrawal Visit). Data from Week 24 (primary endpoint) and Week 48 (final data) are presented in this summary.

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2010
• First Posted: April 13, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 19, 2013
• Results First Posted: December 31, 2012

Record last verified: 2013-09

Locations

US (44); PR (2)