A Phase IIIb Study of the Safety, Efficacy, and Tolerability of Switching to a Fixed-dose Combination of Abacavir/Dolutegravir/ Lamivudine From Current Antiretroviral Regimen
This study is a 48-week, Phase IIIb, randomly assigned, open-label, active-controlled, multicenter, parallel group, non-inferiority study. This study is designed to demonstrate the non-inferior antiviral activity of switching to the Abacavir (ABC) 600 milligrams (mg)/Dolutegravir(DTG) 50 mg/Lamivudine (3TC) 300 mg fixed-dose combination (FDC) compared with continuing the subject's current suppressive regimen through 24 weeks. The study will be conducted in approximately 538 Human Immunodeficiency Virus -1 (HIV-1) infected individuals who are on stable suppressive combination antiretroviral therapy (cART) with 2 Nucleoside reverse transcriptase inhibitors (NRTIs) plus either a protease inhibitor (PI), an non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (INI). Eligible subjects will be randomly assigned 1:1 to continue their current regimen (approximately 269 subjects) or be switched to ABC/DTG/3TC FDC (approximately 269 subjects) once daily for 24 weeks. At Week 24, individuals originally randomly assigned to continue their current regimen will switch to ABC/DTG/3TC FDC and be followed for an additional 24 weeks. Individuals initially randomly assigned to ABC/DTG/3TC FDC will continue on that treatment arm for an additional 24 weeks. A pharmacokinetic (PK) substudy will be conducted at a small number of sites (approximately 5) to evaluate predose DTG concentrations as well as residual drug concentrations of efavirenz (EFV), nevaripine (NVP), amprenavir (APV) and tipranavir (TPV) in a subgroup of subjects who switch from EFV, NVP, fosamprenavir/ritonavir (FPV/r) or tipranavir/ritonavir (TPV/r).
Infection, Human Immunodeficiency Virus
Drug: ABC/DTG/3TC FDC
Drug: Ongoing cART regimen
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||201147: a Phase IIIb, Randomized, Open-label Study of the Safety, Efficacy, and Tolerability of Switching to a Fixed-dose Combination of Abacavir/Dolutegravir/ Lamivudine From Current Antiretroviral Regimen Compared With Continuation of the Current Antiretroviral Regimen in HIV-1 Infected Adults Who Are Virologically Suppressed, The STRIIVING Study.|
- Proportion of subjects with plasma HIV-1 Ribonucleic acid (RNA) <50 copies per millilitre (c/mL) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]Plasma HIV-1 RNA will be measured by HIV-1 Assay with lower limit of detection (LLOD) of 40 c/mL. Additional exploratory methods may be used in some cases.
- Change from Baseline in CD4+ cell counts at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]CD4+ lymphocyte count will be obtained by flow cytometry
- Incidence and severity of adverse events (AEs) over 24 weeks [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
- Incidence and severity of laboratory abnormalities over 24 weeks [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]Laboratory tests will include hematology, clinical chemistry, and urinalysis parameters.
- Proportion of subjects discontinuing treatment due to AEs over 24 weeks [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
- Change from Baseline in fasting lipids at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]Lipid parameters will be assessed in blood samples collected preferably with an overnight fast or after a minimum of a 6-hour fasting
- Change from Baseline in renal, bone, and cardiovascular markers at Week 24Change from Baseline in renal, bone, and cardiovascular markers at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]Blood samples will be collected for bone, cardiovascular and renal marker assessments. Planned assessments include bone specific alkaline phosphatise, procollagen type 1-N-propeptide, type 1 collagen cross-linked C-telopeptide, osteocalcin, Interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), d dimer, Soluble Form of Vascular Cell Adhesion
- Incidence of genotypic and phenotypic resistance in subjects meeting virologic withdrawal criteria over 24 weeks [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]Subjects meeting 'confirmed virologic withdrawal criterion' will have plasma samples tested for HIV-1 protease (PRO), reverse transcriptase (RT) genotype and phenotype, and HIV-1 integrase genotype and phenotype from samples collected at the time of meeting 'suspected virologic withdrawal criterion'
- Change from Baseline in treatment satisfaction assessed by using the HIV Treatment Satisfaction Questionnaire (TSQ) at Week 4 and Week 24 [ Time Frame: Baseline, Week 4, and Week 24 ] [ Designated as safety issue: No ]HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility.
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Subject will take ABC 600 mg/DTG 50 mg/3TC 300 mg FDC once daily in the morning or the evening, at approximately the same time each day for 24 weeks. After Week 24, subjects will continue on this treatment arm for an additional 24 weeks.
Drug: ABC/DTG/3TC FDC
Purple, oval, biconvex tablets containing 702 mg Abacavir sulphate which is equivalent to 600 mg ABC, 52.62 mg Dolutegravir sodium which is equivalent to 50 mg Dolutegravir free acid and 300 mg 3TC
Active Comparator: Comparator
Subjects will continue on their current Combination antiretroviral therapy (cART) regimen for 24 weeks. At Week 24, subjects will switch to ABC/DTG/3TC FDC for an additional 24 weeks.
Drug: Ongoing cART regimen
Stable cART regimens including boosted PI (or ATV unboosted) + 2 NRTIs; NNRTI + 2 NRTIs, or INI (RAL or EVG)+ 2 NRTIs
Please refer to this study by its ClinicalTrials.gov identifier: NCT02131025
|Contact: US GSK Clinical Trials Call Center||877-379-3718||GSKClinicalSupportHD@gsk.com|
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|Study Director:||GSK Clinical Trials||ViiV Healthcare|