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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02831673




Registration number
NCT02831673
Ethics application status
Date submitted
8/07/2016
Date registered
13/07/2016
Date last updated
18/04/2019

Titles & IDs
Public title
An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 1)
Scientific title
A Phase III, Randomised, Double Blind, Multicentre, Parallel Group, Non Inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Dolutegravir Plus Lamivudine Compared to Dolutegravir Plus Tenofovir/Emtricitabine in Human Immunodeficiency Virus 1 Infected Treatment naïve Adults
Secondary ID [1] 0 0
2015-004418-95
Secondary ID [2] 0 0
204861
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infection, Human Immunodeficiency Virus 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dolutegravir (DTG)
Treatment: Drugs - Lamivudine (3TC)
Treatment: Drugs - Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)

Experimental: DTG + 3TC (50 mg+300 mg) - Eligible subjects will receive one 50 mg tablet of DTG plus one overencapsulated 300 mg 3TC tablet orally once daily upto 96 weeks; thereafter will receive DTG plus 3TC tablet upto Week 148 and will continue to receive this schedule until (i) DTG and 3TC are both locally approved for use as part of a dual regimen, and the single entities of DTG and 3TC are available to patients (e.g. through public health services), or (ii) the DTG/3TC FDC tablet, if required by local regulations, is available, , or (iii) the subject no longer derives clinical benefit, or (iv) the subject meets a protocol defined reason for discontinuation, or (v) development of the DTG plus 3TC dual regimen is terminated.

Active Comparator: DTG + TDF/FTC FDC (50 mg+300/200 mg) - Eligible subjects will receive one 50 mg tablet of DTG plus one overencapsulated TDF/ FTC FDC (300/200 mg) tablet orally once daily upto 96 weeks; thereafter will receive DTG plus TDF/FTC FDC tablets upto Week 148 (open-label randomised phase).


Treatment: Drugs: Dolutegravir (DTG)
DTG is available as 50 mg white, round, biconvex, film coated tablet debossed on one side with 'SV 572' and on the other side with '50'. The tablets are packaged into high density polyethylene (HDPE) bottles with induction seals and child resistant closures. Each 45 ml bottle contains 30 tablets and a desiccant. DTG 50 mg tablet will be orally administered once daily with or without food upto 148 weeks.

Treatment: Drugs: Lamivudine (3TC)
Lamivudine is available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg lamivudine to visually match overencapsulated TDF/FTC FDC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated 3TC 300 mg tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, lamivudine will be dispensed as 300 mg white, diamond shaped, scored, film coated tablets debossed with 'GX CJ7' on both sides, packed in over labelled HDPE bottles with child-resistant closures each containing 30 tablets.

Treatment: Drugs: Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)
Tenofovir disoproxil fumarate and Emtricitabine are available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg TDF and 200 mg FTC to visually match overencapsulated 3TC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated tenofovir disoproxil fumarate/emtricitabine tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, tenofovir disoproxil fumarate/emtricitabine will be dispensed as 300/200 mg white, blue, capsule shaped, film coated tablets debossed with 'GILEAD' on one side and '701' on another side, packed in overlabelled HDPE bottles with polypropylene childresistant closures each containing 30 tablets and a desiccant.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48 - Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. 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. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who receive at least one dose of study treatment.
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 - Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel weights.
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Time to Viral Suppression (HIV-1 RNA <50 c/mL) - Time of viral suppression is defined as the first viral load value <50 c/mL. Nonparametric Kaplan-Meier method was performed. Participants who withdrew for any reason without being suppressed were censored at date of withdrawal. Participants who have not been withdrawn and have not had viral suppression at time of the analysis were censored at last viral load date. Confidence Interval (CI) was estimated using the Brookmeyer-Crowley method. Median along with interquartile range (first Quartile and third Quartile) have been presented.
Timepoint [2] 0 0
Up to Week 48
Secondary outcome [3] 0 0
CD4+ Cell Counts 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.
Timepoint [3] 0 0
Weeks 24 and 48
Secondary outcome [4] 0 0
Changes From Baseline in CD4+ Cell Counts at Week 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 the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.
Timepoint [4] 0 0
Baseline (Day 1) and Weeks 24, 48
Secondary outcome [5] 0 0
Number of Participants With HIV-1 Disease Progression - HIV-associated conditions were recorded during the study and was assessed according to the 2014 Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. 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.
Timepoint [5] 0 0
Up to Week 48
Secondary outcome [6] 0 0
Number of Participants With Treatment-emergent Genotypic Resistance - Number of participants, who meet confirmed virologic withdrawal (CVW) criteria, with treatment emergent phenotypic resistance to Integrase strand transfer inhibitor (INSTI) and/or Nucleoside reverse transcriptase inhibitor (NRTI) was summarized. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data.
Timepoint [6] 0 0
Up to Week 48
Secondary outcome [7] 0 0
Number of Participants With Treatment-emergent Phenotypic Resistance - Number of participants, who meet CVW criteria, with treatment 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) and provides the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. Number of participants with phenotype at time of CVW by phenotypic cut-off at or prior to Week 48 have been presented. The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data.
Timepoint [7] 0 0
Up to Week 48
Secondary outcome [8] 0 0
Number of Participants With Any Adverse Event (AE) and Serious AE (SAE) - 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, 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 participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. Safety Population was used which comprised of all participants who received at least one dose of study treatment.
Timepoint [8] 0 0
Up to Week 48
Secondary outcome [9] 0 0
Number of Participants With AEs by Their Severity Grades - 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.
Timepoint [9] 0 0
Up to Week 48
Secondary outcome [10] 0 0
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade - 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 participants with drug related AEs and drug related AEs by maximum grade have been presented.
Timepoint [10] 0 0
Up to Week 48
Secondary outcome [11] 0 0
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities - Blood samples were collected up to Week 48 for assessment of hematology parameters to assess any abnormality per toxicity scales for platelet count, neutrophils, hemoglobin. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 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.
Timepoint [11] 0 0
Up to Week 48
Secondary outcome [12] 0 0
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities - Blood samples were collected up to Week 48 for assessment of Alanine Aminotransferase (ALT), Aspartate aminotransferase (AST), Creatinine, Glucose, Potassium, Sodium, Chloride, Calcium, Total carbon dioxide (CO2), Alkaline phosphatase (ALP), Phosphate, Total bilirubin, Total protein, Albumin, Creatine phosphokinase (CPK), Creatinine clearance,Glomerular filtration rate (GFR), Total cholesterol, High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglyceride and Lipase. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.
Timepoint [12] 0 0
Up to Week 48
Secondary outcome [13] 0 0
Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 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. Data cut-off dates for analysis at Week 24 and Week 48 were 19-Jan-2018 and 22-May-2018 respectively. Number of participants who discontinued treatment due to AEs have been reported.
Timepoint [13] 0 0
Up to Week 48
Secondary outcome [14] 0 0
Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 - Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the latest pre-dose assessment. Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Timepoint [14] 0 0
Baseline and at Weeks 24, 48
Secondary outcome [15] 0 0
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 - Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI (GFR-cystatin C adjusted)and Serum or Plasma GFR from creatinine adjusted using CKD-EPI. Baseline value is the latest pre-dose assessment. Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Timepoint [15] 0 0
Baseline and at Weeks 24, 48
Secondary outcome [16] 0 0
Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 - Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Timepoint [16] 0 0
Baseline and at Weeks 24, 48
Secondary outcome [17] 0 0
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 - Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value is defined as the latest pre-dose assessment. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been presented.
Timepoint [17] 0 0
Baseline and at Weeks 24, 48
Secondary outcome [18] 0 0
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 - Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Timepoint [18] 0 0
Baseline and at Weeks 24, 48
Secondary outcome [19] 0 0
Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48 - Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
Timepoint [19] 0 0
Baseline and at Weeks 24, 48
Secondary outcome [20] 0 0
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 - Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value is defined as the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value).
Timepoint [20] 0 0
Baseline (Day 1) and at Weeks 24, 48
Secondary outcome [21] 0 0
Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48 - Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value).
Timepoint [21] 0 0
Baseline (Day 1) and at Weeks 24, 48
Secondary outcome [22] 0 0
Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 - Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents are not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values.
Timepoint [22] 0 0
Up to Week 48
Secondary outcome [23] 0 0
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 - Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other).
Timepoint [23] 0 0
Week 24
Secondary outcome [24] 0 0
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 - Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other).
Timepoint [24] 0 0
Week 48
Secondary outcome [25] 0 0
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups - 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 the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Timepoint [25] 0 0
Baseline (Day 1) and Week 48
Secondary outcome [26] 0 0
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups - 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 the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age, Gender, and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Timepoint [26] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [27] 0 0
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 - EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has 1 question assessing each of 5 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. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value.
Timepoint [27] 0 0
Baseline and Weeks 4, 24, 48
Secondary outcome [28] 0 0
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 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. 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, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value.
Timepoint [28] 0 0
Baseline (Day 1) and Weeks 4, 24, 48

Eligibility
Key inclusion criteria
- Must be an HIV 1 infected adult >=18 years of age (or older, if required by local
regulations) at the time of signing the informed consent

- An eligible female subject should not be pregnant (as confirmed by a negative serum
human chorionic gonadotrophin (hCG) test at Screening and negative urine test at
Baseline), not lactating, and at least one of the following conditions applies

- Non reproductive premenopausal women are those that have undergone documented
tubal ligation or documented hysteroscopic tubal occlusion procedure with follow
up confirmation of bilateral tubal occlusion or documented bilateral oophorectomy
or hysterectomy

- Non reproductive premenopausal women are those with 12 months of spontaneous
amenorrhea and >=45 years of age

- Women with reproductive potential agree to follow one of the protocol-defined
methods for avoiding pregnancy

- Should have screening plasma HIV 1 RNA levels of 1000 c/mL to <=100,000 c/mL. If an
independent review of accumulated data from other clinical trials investigating the
DTG plus 3TC dual regimen is supportive of the DTG plus 3TC treatment regimen,
enrolment will be opened to subjects with Screening plasma HIV 1 RNA of 1000 c/mL to
<=500,000 c/mL

- Subject should be antiretroviral naïve (defined as <=10 days of prior therapy with any
antiretroviral agent following a diagnosis of HIV 1 infection). Subjects who received
HIV post exposure prophylaxis (PEP) or pre exposure prophylaxis (PrEP) in the past are
allowed as long as the last PEP/PrEP dose was >1 year from HIV diagnosis or there is
documented HIV seronegativity between the last prophylactic dose and the date of HIV
diagnosis

- Subject or the subject's legal representative capable of giving signed informed
consent which includes compliance with the requirements and restrictions listed in the
consent form and the protocol

- Subjects enrolled in France: a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 (CDC, 2014), except cutaneous Kaposi's sarcoma not requiring systemic therapy
and historical or current CD4 cell counts less than 200 cells/mm^3

- 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 or HBV surface antibody (anti-HBs or
HBsAb) based on:

Subjects positive for HBV surface antigen (HBsAg) at screening will be excluded Subjects
negative for HBV core antibody (anti HBs) but positive for anti HBc (negative HBsAg status)
and positive for HBV deoxyribose nucleic acid (DNA) will be excluded; however, subjects
positive for anti HBc (negative HBsAg status) and positive for anti HBs (past and/or
current evidence) are immune to HBV and will not be excluded

- Anticipated need for any hepatitis B virus (HCV) therapy during the first 48 weeks of
the study and for HCV therapy based on interferon or any drugs that have a potential
for adverse drug:drug interactions with study treatment throughout the entire study
period

- Untreated syphilis infection positive RPR at Screening without clear documentation of
treatment. Subjects who are at least 14 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; other localised malignancies require agreement between the
investigator and the Study Medical Monitor for inclusion of the subject

- Subjects who in the Investigator's judgment, poses a significant suicidality risk.
Recent history of suicidal behaviour and/or suicidal ideation may be considered as
evidence of serious suicide 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

- Treatment with any agent, except recognised ART as allowed above, with documented
activity against HIV 1 in vitro within 28 days of first dose of study treatment

- 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 study treatment

- Subjects enrolled in France: the subject has participated in any study using an
investigational drug 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 the subject will participate
simultaneously in another clinical study

- Any evidence of pre existing viral resistance based on the presence of any major
resistance associated mutation in the Screening result or, if known, in any historical
resistance test result

- Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during
the Screening period to verify a result

- 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)

- Creatinine clearance of <50 mL/min per 1.73 m^2 via the chronic kidney disease
epidemiology collaboration (CKD EPI) method

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [3] 0 0
GSK Investigational Site - Fortitude Valley
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
4006 - Fortitude Valley
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Rhode Island
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Belgium
State/province [14] 0 0
Antwerpen
Country [15] 0 0
Belgium
State/province [15] 0 0
Brussels
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
France
State/province [19] 0 0
Le Kremlin-Bicetre Cedex
Country [20] 0 0
France
State/province [20] 0 0
Marseille
Country [21] 0 0
France
State/province [21] 0 0
Paris Cedex 10
Country [22] 0 0
France
State/province [22] 0 0
Paris Cedex 12
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Toulouse Cedex 9
Country [25] 0 0
Germany
State/province [25] 0 0
Bayern
Country [26] 0 0
Germany
State/province [26] 0 0
Nordrhein-Westfalen
Country [27] 0 0
Germany
State/province [27] 0 0
Berlin
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Italy
State/province [29] 0 0
Emilia-Romagna
Country [30] 0 0
Italy
State/province [30] 0 0
Liguria
Country [31] 0 0
Italy
State/province [31] 0 0
Lombardia
Country [32] 0 0
Italy
State/province [32] 0 0
Padova
Country [33] 0 0
Italy
State/province [33] 0 0
Reggio Emilia
Country [34] 0 0
Italy
State/province [34] 0 0
Roma
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Busan
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Daegu
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Mexico
State/province [38] 0 0
Jalisco
Country [39] 0 0
Mexico
State/province [39] 0 0
Distrito Federal
Country [40] 0 0
Netherlands
State/province [40] 0 0
Rotterdam
Country [41] 0 0
Portugal
State/province [41] 0 0
Coimbra
Country [42] 0 0
Portugal
State/province [42] 0 0
Lisboa
Country [43] 0 0
Portugal
State/province [43] 0 0
Porto
Country [44] 0 0
Romania
State/province [44] 0 0
Cluj-Napoca
Country [45] 0 0
Romania
State/province [45] 0 0
Galati
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Ekaterinburg
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Krasnojarsk
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Orel
Country [50] 0 0
Russian Federation
State/province [50] 0 0
St. Petersburg
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Toliyatti
Country [52] 0 0
South Africa
State/province [52] 0 0
Observatory, Cape Town
Country [53] 0 0
Spain
State/province [53] 0 0
Alicante
Country [54] 0 0
Spain
State/province [54] 0 0
Badalona
Country [55] 0 0
Spain
State/province [55] 0 0
Córdoba
Country [56] 0 0
Spain
State/province [56] 0 0
Elche (Alicante)
Country [57] 0 0
Spain
State/province [57] 0 0
Madrid
Country [58] 0 0
Spain
State/province [58] 0 0
Mataró
Country [59] 0 0
Spain
State/province [59] 0 0
San Sebastian
Country [60] 0 0
Spain
State/province [60] 0 0
Santiago de Compostela
Country [61] 0 0
Spain
State/province [61] 0 0
Valencia
Country [62] 0 0
Spain
State/province [62] 0 0
Vigo ( Pontevedra)
Country [63] 0 0
Taiwan
State/province [63] 0 0
Kaohsiung
Country [64] 0 0
Taiwan
State/province [64] 0 0
Taipei
Country [65] 0 0
United Kingdom
State/province [65] 0 0
London
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PPD
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
GlaxoSmithKline
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will compare safety, efficacy, and tolerability of a two drug regimen of
dolutegravir (DTG) plus (+) lamivudine (3TC) administered once daily with DTG plus two
nucleoside reverse transcriptase inhibitors (Tenofovir [TDF]/Emtricitabine [FTC] fixed dose
combination [FDC]) administered once daily in human immunodeficiency virus (HIV) 1 infected
adult subjects that have not previously received antiretroviral therapy. The study is
designed to demonstrate the non-inferior antiviral activity of DTG plus 3TC regimen to that
of DTG plus TDF/FTC FDC and will characterise the long term antiviral activity, tolerability
and safety of DTG plus 3TC through Week 148. Approximately, 700 subjects will be randomised
1:1 to receive DTG + 3TC or DTG + TDF/FTC FDC. Subjects will be stratified by screening HIV 1
ribonucleotide nucleic acid (RNA) levels and by screening CD4+ (cluster of differentiation 4)
cell count.
Trial website
https://clinicaltrials.gov/show/NCT02831673
Trial related presentations / publications
Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Rockstroh JK, Girard PM, Sievers J, Man C, Currie A, Underwood M, Tenorio AR, Pappa K, Wynne B, Fettiplace A, Gartland M, Aboud M, Smith K; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019 Jan 12;393(10167):143-155. doi: 10.1016/S0140-6736(18)32462-0. Epub 2018 Nov 9. Erratum in: Lancet. 2018 Nov 28;:.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications