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Trial record 1 of 1 for:    TANGO dolutegravir
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Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)

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ClinicalTrials.gov Identifier: NCT03446573
Recruitment Status : Active, not recruiting
First Posted : February 27, 2018
Results First Posted : May 4, 2020
Last Update Posted : June 2, 2020
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE January 5, 2018
First Posted Date  ICMJE February 27, 2018
Results First Submitted Date  ICMJE April 16, 2020
Results First Posted Date  ICMJE May 4, 2020
Last Update Posted Date June 2, 2020
Actual Study Start Date  ICMJE January 18, 2018
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2020)
Percentage of Participants With Virologic Failure Endpoint as Per Food and Drug Administration (FDA) Snapshot Category at Week 48 [ Time Frame: Week 48 ]
Percentage of participants with virologic failure (plasma HIV-1 RNA >=50 c/mL) was evaluated using FDA snapshot algorithm at Week 48. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. Intent-to-treat exposed (ITT-E) Population comprises of all randomized participants who receive at least one dose of study treatment either DTG + 3TC or TBR. Participants were assessed according to the treatment to which the participant was randomized. Any participant receiving a treatment randomization number was considered to be randomized.
Original Primary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
Number of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48 [ Time Frame: Week 48 ]
Number of participants with virologic failure was evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks. Plasma samples for HIV-1 RNA was collected at Week 48.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
  • Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Week 48 [ Time Frame: Week 48 ]
    Percentage of participants with plasma HIV-1 RNA <50 c/mL (virologic success) was evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest.
  • Percentage of Participants With Virologic Failure Endpoint as Per FDA Snapshot Category at Week 24 [ Time Frame: Week 24 ]
    Percentage of participants with plasma HIV-1 RNA >=50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest.
  • Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Week 24 [ Time Frame: Week 24 ]
    Percentage of participants with plasma HIV-1 RNA <50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest.
  • Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable.
  • Change From Baseline in CD4+/CD8+ Cell Count Ratio at Weeks 24 and 48 [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio. It was assessed by flow cyclometry to evaluate the immunologic activity of switching to DTG+3TC once daily compared to continuation of TBR over 48 Weeks. Baseline (Day 1) values were the actual CD4+ cell count ratio values at pre-dose Day 1. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable .
  • Number of Participants With Disease Progression at Weeks 24 and 48 [ Time Frame: At Weeks 24 and 48 ]
    HIV-associated conditions were recorded during the study and was assessed according to the 2014 CDC Classification System for HIV Infection in Adults. CDC classification for HIV were: Stage 1: No AIDS defining condition and CD4+ T-lymphocyte count: >=500 cells/mcL; Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3: with HIV infection and CD4+ T-lymphocye count <200 cells/mcL. Disease progression summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrolment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrolment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death.
  • Number of Participants With Any Serious Adverse Events (SAEs) and Common (>=2%) Non-serious Adverse Events (Non-SAEs) [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population included all participants who received at least one dose of study treatment either DTG + 3TC or TBR. This population was based on the treatment the participant actually received. Number of participants with any SAE and common (>=2%) non-SAEs are presented.
  • Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Any SAEs and Common (>=2%) Non-SAEs [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Number of TDF-based regimen participants with any SAE and common (>=2%) non-SAEs are presented.
  • Number of Participants With AEs by Their Severity Grades [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.
  • Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With AEs by Their Severity Grades [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of TDF-based regimen participants with adverse events by maximum grade have been presented.
  • Number of Participants Who Discontinued the Treatment Due to AEs [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented.
  • Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen Who Discontinued the Treatment Due to AEs [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented.
  • Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities [ Time Frame: Up to Week 48 ]
    Blood samples were collected up to Week 48 for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.
  • Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Maximum Post-Baseline Emergent Hematology Toxicities [ Time Frame: Up to Week 36 ]
    Blood samples were collected up to the Week 36 visit for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those TDF-based regimen participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.
  • Number of Participants With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities [ Time Frame: Up to Week 48 ]
    Blood samples were collected up to Week 48 for the analysis of clinical chemistry parameters: alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotransferase (AST), bilirubin, carbon dioxide (CO2), cholesterol, creatinine kinase (CK), creatinine, direct bilirubin, glomerular filtration rate (GFR) from creatinine adjusted for body surface area (BSA), GFR from cystatin C adjusted using chronic kidney disease-epidemiology collaboration (CKD-EPI), hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol, phosphate and triglycerides. Any abnormality in clinical chemistry parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.
  • Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities [ Time Frame: Up to Week 36 ]
    samples were collected up to the Week 36 visit for the analysis of clinical chemistry parameters: alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotransferase (AST), bilirubin, carbon dioxide (CO2), cholesterol, creatinine kinase (CK), creatinine, direct bilirubin, glomerular filtration rate (GFR) from creatinine adjusted for body surface area (BSA), GFR from cystatin C adjusted using chronic kidney disease-epidemiology collaboration (CKD-EPI), hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol, phosphate and triglycerides. Any abnormality in clinical chemistry parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.
  • Change From Baseline in Renal Biomarkers- Urine Albumin/Creatinine (UA/C) Ratio and Urine Protein/Creatinine (UP/C) Ratio at Weeks 24 and 48 [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine samples were collected at Baseline, Week 24 and Week 48. Baseline is defined as Day 1. Change from Baseline in UA/C was calculated as UA/C ratio at post-Baseline visit minus UA/C ratio calculated at Baseline. Estimated geometric mean adjusted ratio (each visit over Baseline) and 95% CI have been presented. Change from Baseline in UP/C and UA/C was calculated as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio calculated at Baseline, respectively. Estimated geometric mean adjusted ratio (each visit over Baseline) and 95% CI have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- UA/C Ratio and UP/C Ratio at Weeks 24 and 48 in Participants Randomized to TBR Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine samples were collected at Baseline, Week 24 and Week 48 to assess renal biomarkers - urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline in UA/C was calculated as UA/C ratio at post-Baseline visit minus UA/C ratio calculated at Baseline. Change from Baseline in UP/C was calculated as UP/C ratio at post-Baseline visit minus UP/C ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine biomarker samples were collected at Baseline and Week 48 to assess urine beta-2 microglobulin/urine creatinine. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine biomarker samples were collected to assess urine beta-2 microglobulin/urine creatinine. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- Urine Phosphate [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine biomarker samples were collected at Baseline and at Weeks 24 and 48 to assess urine phosphate. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- Urine Phosphate in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine biomarker samples were collected to assess urine phosphate. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine biomarker samples were collected at Baseline and Week 48 to assess urine retinol binding protein 4/urine creatinine. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in Urine retinol binding protein 4/urine creatinine ratio was calculated as Urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus Urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Urine biomarker samples were collected to assess urine retinol binding protein 4/urine creatinine. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine retinol binding protein 4/urine creatinine was calculated as urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Fasting Lipids at Weeks 24 and 48 [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma high density lipoprotein (HDL) cholesterol and plasma triglycerides. Baseline value was the value from the latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Fasting Lipids at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at weeks 24 and 48 ]
    Blood samples were collected up to the Week 48 visit (participant withdrew from the study at Week 36) to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma HDL cholesterol and plasma triglycerides. Baseline value was the value from the latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for fasting lipids in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Number of Participants With Genotypic Resistance [ Time Frame: Up to Week 48 ]
    Plasma samples were collected for drug resistance testing. Number of participants, who met confirmed virologic withdrawal (CVW) criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with emergent genotypic resistance to INSTI, nucleoside reverse transcriptase inhibitor (NRTI), NNRTI and PI was summarized.
  • Number of Participants With Phenotypic Resistance [ Time Frame: Up to Week 48 ]
    Number of participants, who meet CVW criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with emergent phenotypic resistance to INSTI and/or NRTI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences), which provided the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The phenotypic resistance was calculated using binary scoring system, where 0 was considered as sensitive and 1 as resistance. Phenotypic Resistance data for the following INSTI, NNRTI, NRTI and PI drugs in participants Meeting CVW Criteria has been presented.
  • Change From Baseline in Bone Biomarkers-serum Bone-specific ALP (Bone-ALP), Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Type 1 Collagen C-telopeptides (CTX-1) [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected for analysis of bone biomarkers. Baseline was latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, body mass index (BMI) (continuous), smoking status, vitamin D use, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Bone Biomarkers-serum Bone-specific ALP (Bone-ALP), Osteocalcin, Serum P1NP and Serum CTX-1 in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected for analysis of bone biomarkers. Baseline was latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected for analysis of 25-hydroxyvitamin D. Baseline value was latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, BMI (continuous), smoking status, vitamin D use, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected for the analysis of 25-hydroxyvitamin D. Baseline value was the value from latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum 25-hydroxyvitamin D in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarker- Serum Cystatin C [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected to assess renal biomarker. Baseline was latest pre-dose assessment value (Day 1) with non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for following:treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarker- Serum Cystatin C in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - cystatin C. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum cystatin -C biomarker in TDF based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24 and 48 [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected to assess serum GFR from cystatin C and from creatinine adjusted using CKD-EPI. Baseline was Day 1 with non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarkers - serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarker- Serum Creatinine [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected to assess renal inflammation biomarker - serum creatinine. Baseline was Day 1 with a non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, BMI (continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in Renal Biomarker- Serum Creatinine in Participants Randomized to TBR Arm Receiving TDF-based Regimen [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - serum creatinine. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum creatinine in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
  • Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score at Week 24 and 48 [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health.
  • Change From Baseline in EQ-5D-5L Thermometer Scores at Week 24 and 48 [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    EEQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
  • Number of participants with plasma HIV-1 RNA <50 c/mL at Weeks 24 and 48 using the Snapshot algorithm [ Time Frame: Week 24 and Week 48 ]
    Number of participants with plasma HIV-1 RNA <50 c/mL were evaluated using the FDA snapshot algorithm at Weeks 24 and 48 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 24 and 48 weeks. Plasma samples for HIV-1 RNA were collected at Week 24 and Week 48.
  • Number of participants with virologic failure endpoint as per FDA snapshot category at Week 24 [ Time Frame: Week 24 ]
    Number of participants with virologic failure was evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 24 weeks. Plasma samples for HIV-1 RNA was collected at Week 24 .
  • Change from Baseline in CD4+ lymphocyte count at Weeks 24 and 48 [ Time Frame: Baseline and up to Week 48 ]
    Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Weeks 24 and 48 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected at Week 0 (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48.
  • Change from Baseline in CD4+/CD8+ cell count ratio [ Time Frame: Baseline and up to Week 48 ]
    Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+/CD8+ cell count ratio was assessed at Weeks 24 and 48 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected at Week 0 (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48.
  • Number of participants with HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death through Weeks 24 and 48 [ Time Frame: Up to Week 48 ]
    HIV-associated conditions will be assessed according to the 2014 CDC Classification System for HIV Infection in Adults to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR.
  • Number of participants with any adverse event (AE), serious AE (SAE), SAE and AE leading to discontinuation through 24 and 48 weeks [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward event that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. An SAE may also include any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the safety of the participant or may require medical or surgical intervention. Number of participant with any AE, SAE, or AE leading to discontinuation through 24 and 48 weeks will be summarized.
  • Number of participants with laboratory abnormalities through 24 and 48 weeks [ Time Frame: Up to Week 48 ]
    Blood samples will be collected at Week 0 (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48 to evaluate laboratory parameters.
  • Time to first Adverse Event (AE) [ Time Frame: Up to Week 48 ]
    Time to first AE will be assessed to evaluate the safety and tolerability of DTG + 3TC once daily compared to TBR over time.
  • Change from Baseline in total cholesterol at Weeks 24 and 48 [ Time Frame: Up to Week 48 ]
    Blood samples will be collected at Week 0 (Day 1), 24 and 48 to assess total cholesterol.
  • Change from Baseline in low density lipoprotein (LDL) cholesterol at Weeks 24 and 48 [ Time Frame: Up to Week 48 ]
    Blood samples will be collected at Week 0 (Day 1), 24 and 48 to assess low density lipoprotein (LDL) cholesterol.
  • Change from Baseline in high density lipoprotein (HDL) cholesterol at Weeks 24 and 48 [ Time Frame: Up to Week 48 ]
    Blood samples will be collected at Week 0 (Day 1), 24 and 48 to assess high density lipoprotein (HDL) cholesterol.
  • Change from Baseline in triglycerides at Weeks 24 and 48 [ Time Frame: Up to Week 48 ]
    Blood samples will be collected at Week 0 (Day 1), 24 and 48 to assess triglycerides.
  • Number of participants with observed genotypic and phenotypic resistance to antiretrovirals (ARVs) for participants meeting Virologic Withdrawal Criteria [ Time Frame: Up to Week 48 ]
    Blood samples will be collected at Week 0 (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48 for potential viral genotypic and phenotypic analyses to assess viral resistance. Participants meeting Confirmed Virologic Withdrawal (CVW) or Precautionary Virologic Withdrawal (PVW) criteria will have plasma samples tested for HIV-1 protease (PRO), reverse transcriptase (RT), and integrase (IN) genotypic and phenotypic resistance. The earliest plasma sample with HIV-1 RNA ≥200 c/mL will be used for this resistance testing.
  • Change from Baseline in Cystatin C [ Time Frame: Baseline and up to Week 48 ]
    Blood and urine samples will be collected for Cystatin C at Week 0 (Day 1) and at Weeks 24 and 48.
  • Change from Baseline in Beta-2-Microglobulin [ Time Frame: Baseline and up to Week 48 ]
    Blood and urine samples will be collected for Beta-2-Microglobulin at Week 0 (Day 1) and at Weeks 24 and 48
  • Change from Baseline in Retinol Binding Protein [ Time Frame: Baseline and up to Week 48 ]
    Blood and urine samples will be collected for Retinol Binding Protein at Week 0 (Day 1) and at Weeks 24 and 48
  • Change from Baseline in bone specific alkaline phosphatase at Weeks 24 and 48 [ Time Frame: Baseline and up to Week 48 ]
    Blood samples will be collected for bone specific alkaline phosphatase at Week 0 (Day 1) and at Weeks 24 and 48.
  • Change from Baseline in procollagen type 1-N-propeptide at Weeks 24 and 48 [ Time Frame: Baseline and up to Week 48 ]
    Blood samples will be collected for procollagen type 1-N-propeptide at Week 0 (Day 1) and at Weeks 24 and 48.
  • Change from Baseline in type 1 collagen cross-linked C-telopeptide at Weeks 24 and 48 [ Time Frame: Baseline and up to Week 48 ]
    Blood samples will be collected for type 1 collagen cross-linked C-telopeptide at Week 0 (Day 1) and at Weeks 24 and 48.
  • Change from Baseline in osteocalcin at Weeks 24 and 48 [ Time Frame: Baseline and up to Week 48 ]
    Blood samples will be collected for osteocalcin at Week 0 (Day 1) and at Weeks 24 and 48.
  • Change from Baseline in 25 hydroxy-Vitamin D at Weeks 24 and 48 [ Time Frame: Baseline and up to Week 48 ]
    Blood samples will be collected for 25 hydroxy-Vitamin D at Week 0 (Day 1) and at Weeks 24 and 48.
  • Change from Baseline in health status using European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Weeks 24 and 48 (or Withdrawal from the study) [ Time Frame: Baseline and up to Week 48 ]
    The EQ-5D-5L is a standardized, generic questionnaire that provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: 1) mobility, 2) self-care, 3) usual activities, 4) pain/discomfort, and 5) anxiety/depression, and 5 levels for each dimension (no problems, slight problems, moderate problems, severe problems and extreme problems). The EQ-5D-5L also includes a visual analog scale (VAS) that assesses overall health. EQ-5D-5L will be conducted at Week 0 (Day 1) and at Week 4, 24 and 48.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)
Official Title  ICMJE A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Dolutegravir Plus Lamivudine in HIV-1 Infected Adults Who Are Virologically Suppressed
Brief Summary

The aim of the study is to establish if human immunodeficiency virus type 1 (HIV-1) infected adult subjects with current virologic suppression on a ≥3-drug tenofovir alafenamide (TAF) based regimen (TBR) remain suppressed upon switching to a two-drug regimen of dolutegravir (DTG) 50 milligram (mg) + lamivudine (3TC) 300 mg. This study will also provide important information regarding the safety and subject satisfaction with this two-drug regimen. The primary objective of this trial is to demonstrate the non-inferior antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 48 weeks in HIV-1 infected, ART-experienced, virologically suppressed subjects. This study also will characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC compared to TBR through Week 144 and characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC through Week 200.

This will be a 200-week, Phase III, randomized, open-label, active-controlled, multicenter, parallel-group study. The study will include a screening phase (up to 28 days), a randomized early switch phase (Day 1 up to Week 148), a randomized late switch phase (Week 148 up to Week 200), and a continuation phase (post Week 200). Approximately 550 HIV-1 infected adults on stable TBR will be randomized 1:1 to switch to DTG + 3TC once daily for up to 200 weeks, or to continue their TBR for 148 weeks, at which time and if HIV-1 ribonucleic acid (RNA) <50 copies per milliliter (c/mL) at Week 144, these subjects will switch to DTG + 3TC up to Week 200.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a randomized study with parallel group assignment where subjects will be randomized into one of the two treatment groups. Subjects randomized to DTG + 3TC will receive DTG + 3TC up to Week 200. Subjects randomized to TBR will continue to take their current regimen up to Week 148, at which time and if HIV-1 RNA <50 c/mL at Week 144, these subjects will switch to DTG + 3TC up to Week 200. Randomization will be stratified by Baseline third agent class (protease inhibitor [PI], integrase inhibitor [INI], or non-nucleoside reverse transcriptase inhibitor [NNRTI]).
Masking: None (Open Label)
Masking Description:
This will be an open-label study and therefore no blinding is required. The Sponsor team aims to remain blinded to subject assignment, and will instruct sites to refrain from mentioning assignment when sending in queries (as the sites/subjects will not be blinded). No summaries of the study data according to actual randomized treatment groups will be available to sponsor staff prior to the planned Week 24 preliminary analysis.
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: DTG + 3TC
    DTG+3TC is supplied as white, oval, film-coated, fixed dose combination tablet. The tablets will be available in packed high density polyethylene (HDPE) bottles with induction seals and child-resistant closures.
  • Drug: TAF based regimen (TBR)
    Subjects will continue to receive their TBR.
Study Arms  ICMJE
  • Experimental: DTG + 3TC 50 mg/300 mg
    Subjects will receive a single tablet of a two-drug regimen of DTG 50 mg + 3TC 300 mg once daily from Day 1 through Week 200 (Early and Late Switch Phase).
    Intervention: Drug: DTG + 3TC
  • Active Comparator: TAF based regimen (TBR)
    Subjects will continue their TBR from Day 1 to Week 148 (Early Switch Phase), and eligible subjects will switch to DTG + 3TC once daily from Week 148 to 200 (Late Switch Phase).
    Intervention: Drug: TAF based regimen (TBR)
Publications * van Wyk J, Ajana F, Bisshop F, De Wit S, Osiyemi O, Portilla J, Routy JP, Wyen C, Ait-Khaled M, Nascimento MC, Pappa KA, Wang R, Wright J, Tenorio AR, Wynne B, Aboud M, Gartland MJ, Smith KY. Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose Two-Drug Regimen Versus Continuing a Tenofovir Alafenamide-Based Three- or Four-Drug Regimen for Maintenance of Virologic Suppression in Adults With HIV-1: Phase 3, Randomized, Non-inferiority TANGO Study. Clin Infect Dis. 2020 Jan 6. pii: ciz1243. doi: 10.1093/cid/ciz1243. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 19, 2019)
743
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2018)
550
Estimated Study Completion Date  ICMJE May 13, 2022
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject must be able to understand and comply with protocol requirements, instructions, and restrictions;
  • Subject must be likely to complete the study as planned;
  • Subject must be considered an appropriate candidate for participation in an investigative clinical trial with medication (e.g. no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country).
  • Aged 18 years or older (older where required by local regulatory agencies), at the time of signing the informed consent.
  • HIV-1 infected men or women.
  • Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.
  • Plasma HIV-1 RNA <50 c/mL at Screening.
  • Must be on uninterrupted ART for at least 6 months prior to screening. Only the following regimens are allowed:

    • Subject on a TAF-based regimen for at least 6 months, or
    • Subjects who switched from tenofovir disoproxil fumarate (TDF) (as part of first-line regimen) to tenofovir alafenamide (TAF), without any changes to the other drugs in their regimen, and have been on the TAF-based regimen for at least 3 months immediately prior to Screening. The switch must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for suspected or established treatment failure.
  • A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at randomization), not lactating, and at least one of the following conditions applies:

    a. Non-reproductive potential defined as:

  • Pre-menopausal females with one of the following:

    • Documented tubal ligation
    • Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
    • Hysterectomy
    • Documented bilateral oophorectomy
  • Post-menopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

    b. Reproductive potential and agrees to follow highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) from 30 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication.

  • The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. All subjects participating in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions of the consent form and the protocol. Eligible subjects or their legal guardians must sign a written informed consent form before any protocol-specified assessments are conducted.

Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

  • Women who are breastfeeding or plan to become pregnant or breastfeed during the study.
  • Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease, EXCEPT cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/millimeter (mm)^3 are NOT exclusionary.
  • Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: subjects positive for HBsAg are excluded; subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.

Note: Subjects positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Anti-HBc must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and NOT anti-HBc IgM.

  • Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study, for HCV therapy based on interferon or for any drugs that have a potential for adverse drug-drug interactions with study treatment throughout the entire study period.
  • Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Subjects who are at least 7 days post completed treatment are eligible.
  • History or presence of allergy or intolerance 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, anal or penile intraepithelial neoplasia.
  • Subjects who in the investigator's judgment, poses a significant suicidality risk.
  • 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 systemic immune suppressant.
  • 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 investigational product (IP).
  • Use of any regimen consisting of single or dual ART.
  • Any evidence of major nucleoside reverse transcriptase inhibitor (NRTI) mutation or presence of any major INSTI resistance-associated mutation in any available prior resistance genotype assay test result, if known.
  • Any verified Grade 4 laboratory abnormality.
  • Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3 times ULN and bilirubin ≥1.5 times ULN (with >35% direct bilirubin).
  • Creatinine clearance of <50 mL/minute/1.73 meter^2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method.
  • Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.
  • Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements ≥50 c/mL.
  • Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement ≥50 c/mL.
  • Any drug holiday during the 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
  • Any history of switch to another regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA ≥400 c/mL.
  • Subjects enrolled in France (or in other countries as required by local regulations or Ethics Committee/Institutional Review Board [IRB]) who:

    • Participated in any study using an investigational drug or vaccine during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study, or
    • Participate simultaneously in another clinical study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Japan,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries Denmark,   Finland,   Italy,   Korea, Republic of,   Puerto Rico,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT03446573
Other Study ID Numbers  ICMJE 204862
2015-004401-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request Site
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP