Clinical trial NCT01910402: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infection, Human Immunodeficiency Virus
HIV Infections
Keywords: antiretroviral therapy naïve
women
once daily
HIV infection
atazanavir
tenofovir/emtricitabine
dolutegravir/abacavir/lamivudine fixed dose combination
integrase inhibitor
ritonavir
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2013-07-29
Enrollment: 499
Sex: FEMALE
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 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)


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA <50 and <400 c/mL Over Time-Randomized Phase
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL in Continuation Phase
timeFrame: Week 96 and Week 432
measure: Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase
timeFrame: Baseline (Day 1), Week 96 and Week 432
measure: Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase
timeFrame: Week 96 and Week 432
measure: Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Randomized Phase
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Continuation Phase
timeFrame: Baseline (Day 1), Week 96, Week 432
measure: Absolute Values in CD4+ Cell Count at Indicated Timepoints-Randomized Phase
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Absolute Values in CD4+ Cell Count at Indicated Timepoints-Continuation Phase
timeFrame: Week 96 and Week 432
measure: Change From Baseline in Carbon Dioxide, Electrolytes, Lipids, Glucose, Urea at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Bilirubin and Creatinine at Indicated Timepoints
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Albumin at Indicated Timepoints
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Creatinine Clearance at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Lipase at Indicated Timepoints
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Total CHLS/HDL CHLS Ratio at Indicated Timepoints
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Erythrocytes at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Hematocrit Count at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Erythrocyte Mean Corpuscular Volume at Indicated Time Points
timeFrame: Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in Triglycerides at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in TC/HDL Ratio at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Urine Albumin Creatinine Ratio at Indicated Time Points
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Number of Participants With AEs by Maximum Toxicity-Randomized Phase
timeFrame: Up to Week 48
measure: Number of Participants With AEs by Maximum Toxicity-Continuation Phase
timeFrame: From Weeks 48 to 432
measure: Number of Participants With Any Adverse Events (AEs), and Serious Adverse Events (SAEs)-Randomized Phase
timeFrame: Up to Week 48
measure: Number of Participants With Any AEs, and SAEs in Continuation Phase
timeFrame: From Weeks 48 to 432
measure: Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Randomized Phase
timeFrame: Up to Week 48
measure: Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Continuation Phase
timeFrame: From Weeks 48 to 432
measure: Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Randomized Phase
timeFrame: Up to Week 48
measure: Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Continuation Phase
timeFrame: From Weeks 48 to 432
measure: Number of Participants Who Withdrew From Treatment Due to AEs-Randomized Phase
timeFrame: Up to Week 48
measure: Number of Participants Who Withdrew From Treatment Due to AEs-Continuation Phase
timeFrame: From Weeks 48 to 432
measure: Change From Baseline in Bone Specific Alkaline Phosphatase, Osteocalcin and Procollagen 1 N-terminal Propeptide at Indicated Timepoints
timeFrame: Baseline (Day 1), Weeks 24 and 48
measure: Change From Baseline in Type I Collagen C-telopeptides at Indicated Timepoints
timeFrame: Baseline (Day 1), Weeks 24 and 48
measure: Change From Baseline in Vitamin D, Vitamin D2 and Vitamin D3 at Week 24 and Week 48
timeFrame: Baseline (Day 1), Weeks 24 and 48
measure: Bone Specific Alkaline Phosphatase, Osteocalcin, Procollagen 1 N-terminal Propeptide, Type 1 Collagen C-Telopeptide, Vitamin D Ratio of Week 48 Results Over Baseline
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline at Week 48 in SF-12 Total Score, MCS and PCS
timeFrame: Baseline (Day 1) and Week 48
measure: HIVTSQs Total Score at Indicated Timepoints
timeFrame: Weeks 4, 12, 24 and 48
measure: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 by Subgroups
timeFrame: Week 48
measure: Number of Participants With Post-Baseline HIV-1 Disease Progression-Randomized Phase
timeFrame: Up to week 48
measure: Number of Participants With Post-Baseline HIV-1 Disease Progression for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase)
timeFrame: Up to week 432
measure: Number of Participants With Treatment Emergent Resistances for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase)
timeFrame: Up to week 432
measure: Number of Participants With Treatment Emergent Resistances for ATV 300 mg+RTV 100 mg+TDF 300 mg/FTC 200mg QD (Randomized Phase)
timeFrame: Up to week 48
Other outcomes:
Locations:
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: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Pierce
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: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Neptune
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
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: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Allentown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Bellaire
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Bobigny
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Bergamo
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Brescia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Busto Arsizio (VA)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Mexico
country: Mexico
facility: GSK Investigational Site
city: Amadora
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Ponce
country: Puerto Rico
facility: GSK Investigational Site
city: Rio Piedras
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Orel
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Toliyatti
country: Russian Federation
facility: GSK Investigational Site
city: Observatory, Cape Town
country: South Africa
facility: GSK Investigational Site
state: Western Province
city: Mamelodi East
country: South Africa
facility: GSK Investigational Site
city: (Móstoles) Madrid
country: Spain
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Nonthaburi
country: Thailand
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
city: Tooting, London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Orrell C, Hagins DP, Belonosova E, Porteiro N, Walmsley S, Falco V, Man CY, Aylott A, Buchanan AM, Wynne B, Vavro C, Aboud M, Smith KY; ARIA study team. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV. 2017 Dec;4(12):e536-e546. doi: 10.1016/S2352-3018(17)30095-4. Epub 2017 Jul 17.