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)

ViiV Healthcare

Status and phase: Completed; Phase 3

Conditions: Infection, Human Immunodeficiency Virus; HIV Infections

Treatments: Drug: Atazanavir; Drug: Tenofovir/emtricitabine FDC; Drug: Ritonavir; Drug: Dolutegravir/abacavir/lamivudine FDC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01910402

2012-005823-34 (EudraCT Number)

117172

Details and patient eligibility

About

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)

Enrollment: 499 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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499 participants in 2 patient groups

DTG/ABC/3TC FDC

Experimental group

Description:

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

Treatment:

Drug: Dolutegravir/abacavir/lamivudine FDC

ATV +RTV +TDF/FTC FDC

Active Comparator group

Description:

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

Treatment:

Drug: Tenofovir/emtricitabine FDC

Drug: Atazanavir

Drug: Ritonavir