A Study to Determine Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) in Human Immunodeficiency Virus (HIV)-1 Infected Antiretroviral Therapy (ART) Naïve Women (ARIA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by ViiV Healthcare
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01910402
First received: July 25, 2013
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)


Condition Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: Dolutegravir/abacavir/lamivudine FDC
Drug: Atazanavir
Drug: Ritonavir
Drug: Tenofovir/emtricitabine FDC
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IIIb, Randomized, Open-label Study of the Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine Once Daily Compared to Atazanavir and Ritonavir Plus Tenofovir/Emtricitabine Once Daily in HIV-1 Infected Antiretroviral Therapy Naïve Women

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Proportion of subjects with plasma HIV-1 ribonucleic acid (RNA) <50 copies/milliliter (c/mL) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 will be assessed. Plasma samples will be collected for the quantitative assessment of HIV-1 RNA based on the Snapshot algorithm.


Secondary Outcome Measures:
  • Proportion of subjects with plasma HIV-1 RNA <50 c/mL and <400 c/mL over time [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
    The proportion of participants with plasma HIV-1 RNA <50 c/mL and <400 c/mL will be assessed

  • Absolute values and change from Baseline in plasma HIV-1 RNA over time [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
  • Absolute values and changes from Baseline in CD4+ cell counts over time [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
    Blood sample will be collected for measurement of lymphocyte subset CD4+ cells count

  • Incidence of disease progression [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
    Incidence of disease progression includes number of subjects with HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death

  • Incidence and severity of adverse events (AEs) and proportion of subjects who discontinue treatment due to AEs [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
  • Incidence, severity, absolute values and changes over time in laboratory parameters abnormalities [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
    Absolute values and change over time will be assessed for laboratory test results includes: hematology, clinical chemistry, and urinalysis

  • Change from Baseline in fasting lipids and glucose [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Blood samples will be collected to assess change from Baseline in fasting lipid and glucose concentration

  • Changes from Baseline in renal and bone markers [ Time Frame: Up to Week 48 (and beyond week 48 for renal markers in DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
    Urine and blood samples will be collected for assessment of renal markers, and blood sample wil be collected for assessment of bone markers

  • Change from Baseline in health related quality of life and treatment satisfaction [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline in health related quality of life will be assessed using SF-12 (12-Item Short Form Health Survey) and treatment satisfaction will be assessed using the HIV Treatment Satisfaction Questionnaire (HIVTSQ), a 10-item self-reported scale

  • Incidence of treatment emergent genotypic and phenotypic resistance in subjects who meet confirmed virologic withdrawal criteria [ Time Frame: Up to Week 48 (and beyond week 48 for DTG/ABC/3TC arm) ] [ Designated as safety issue: No ]
    Blood samples will be obtained for viral genotypic and phenotypic analyses


Estimated Enrollment: 474
Study Start Date: August 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DTG/ABC/3TC FDC
As per the randomization schedule subjects will be administered with DTG/ABC/3TC (50mg/600mg/300mg) FDC tablet OD up to Week 48 and if continued if applicable in the Continuation Phase. DTG/ABC/3TC FDC may be administered with or without food
Drug: Dolutegravir/abacavir/lamivudine FDC
Dolutegravir/abacavir/lamivudine FDC tablets, 50 mg/600 mg/300 mg
Active Comparator: ATV +RTV +TDF/FTC FDC
As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food
Drug: Atazanavir
Atazanavir capsule 300 mg
Drug: Ritonavir
Ritonavir tablet 100 mg
Drug: Tenofovir/emtricitabine FDC
Tenofovir/emtricitabine FDC tablet 300 mg/200 mg of FTC

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected females (gender at birth) >=18 years of age
  • Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
  • HIV-1 infection as documented by Screening plasma HIV-1 RNA >=500 c/mL.
  • Documentation that the subject is negative for the HLA-B*5701 allele.
  • Antiretroviral-naïve (<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection).
  • Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.

Exclusion Criteria:

  • Women who are pregnant or breastfeeding
  • Women who plan to become pregnant during the first 48 weeks of the study
  • Any subject who has had a medical intervention for gender reassignment
  • Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease
  • Subjects with any degree of hepatic impairment
  • Subjects positive for hepatitis B at Screening, or anticipated need for HCV therapy during the study
  • History or presence of allergy to the study drugs or their components or drugs of their class
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia
  • poses a significant suicidality risk
  • History of osteoporosis with fracture or requiring pharmacologic therapy
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
  • Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses;
  • Treatment with any agent, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product (IP)
  • Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP
  • Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result
  • Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities (total cholesterol, triglycerides, High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) cholesterol)
  • Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound
  • Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin)
  • Subject has CrCL of <50 mL/min via Cockroft-Gault method
  • Corrected QT interval (QTc (Bazett)) ≥450msec or QTc (Bazett) ≥480msec for subjects with bundle branch block.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01910402

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 92 Study Locations
Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

No publications provided

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01910402     History of Changes
Other Study ID Numbers: 117172
Study First Received: July 25, 2013
Last Updated: July 10, 2014
Health Authority: Mexico: Ministry of Health
Portugal: The National Institue of Pharmacy and Medicines (Infarmed)
Italy: Italian Medicines Agency
Argentina: Ministry of Health - A.N.M.A.T
South Africa: Medicines Control Council
Thailand: Food and Drug Administration
United States: Food and Drug Administration
Russia: Russian Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: National Agency for the Safety of Medicine and Health Products
Spain: Spanish Agency for Medicines and Health Products
Canada: Health Canada

Keywords provided by ViiV Healthcare:
antiretroviral therapy naïve
women
once daily
HIV infection
atazanavir
tenofovir/emtricitabine
dolutegravir/abacavir/lamivudine fixed dose combination
integrase inhibitor
ritonavir

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Lamivudine
Tenofovir
Tenofovir disoproxil
Abacavir
Ritonavir
Atazanavir
Emtricitabine
Integrase Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014