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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03446573




Registration number
NCT03446573
Ethics application status
Date submitted
5/01/2018
Date registered
19/02/2018
Date last updated
26/11/2018

Titles & IDs
Public title
Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)
Scientific title
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
Secondary ID [1] 0 0
2015-004401-17
Secondary ID [2] 0 0
204862
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DTG + 3TC
Treatment: Drugs - TAF based regimen (TBR)

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).

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).


Treatment: Drugs: 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.

Treatment: Drugs: TAF based regimen (TBR)
Subjects will continue to receive their TBR.

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

Outcomes
Primary outcome [1] 0 0
Number of subjects with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48 - Number of subjects 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.
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Number of subjects with plasma HIV-1 RNA <50 c/mL at Week 24 using the Snapshot algorithm - Number of subjects with plasma HIV-1 RNA <50 c/mL were evaluated using the FDA snapshot algorithm at Week 24 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 were collected at Week 24.
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Number of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using the Snapshot algorithm - Number of subjects with plasma HIV-1 RNA <50 c/mL were evaluated using the FDA snapshot algorithm at Week 48 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 48 weeks. Plasma samples for HIV-1 RNA were collected at Week 48.
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Number of subjects with plasma HIV-1 RNA <50 c/mL at Week 96 using the Snapshot algorithm - Number of subjects with plasma HIV-1 RNA <50 c/mL were evaluated using the FDA snapshot algorithm at Week 96 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 96 weeks. Plasma samples for HIV-1 RNA were collected at Week 96.
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Number of subjects with plasma HIV-1 RNA <50 c/mL at Week 144 using the Snapshot algorithm - Number of subjects with plasma HIV-1 RNA <50 c/mL were evaluated using the FDA snapshot algorithm at Week 144 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 144 weeks. Plasma samples for HIV-1 RNA were collected at Week 144.
Timepoint [4] 0 0
Week 144
Secondary outcome [5] 0 0
Number of subjects with virologic failure endpoint as per FDA snapshot category at Week 24 - Number of subjects 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.
Timepoint [5] 0 0
Week 24
Secondary outcome [6] 0 0
Number of subjects with virologic failure endpoint as per FDA snapshot category at Week 96 - Number of subjects with virologic failure was evaluated using FDA snapshot algorithm at Week 96 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 96 weeks. Plasma samples for HIV-1 RNA was collected.
Timepoint [6] 0 0
Week 96
Secondary outcome [7] 0 0
Number of subjects with virologic failure endpoint as per FDA snapshot category at Week 144 - Number of subjects with virologic failure was evaluated using FDA snapshot algorithm at Week 144 to demonstrate the antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 144 weeks. Plasma samples for HIV-1 RNA was collected.
Timepoint [7] 0 0
Week 144
Secondary outcome [8] 0 0
Change from Baseline in CD4+ lymphocyte count at Week 24 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 24 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [8] 0 0
Baseline and Week 24
Secondary outcome [9] 0 0
Change from Baseline in CD4+ lymphocyte count at Week 48 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 48 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [9] 0 0
Baseline and Week 48
Secondary outcome [10] 0 0
Change from Baseline in CD4+ lymphocyte count at Week 96 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 96 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [10] 0 0
Baseline and Week 96
Secondary outcome [11] 0 0
Change from Baseline in CD4+ lymphocyte count at Week 144 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 144 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [11] 0 0
Baseline and Week 144
Secondary outcome [12] 0 0
Change from Baseline in CD4+/CD8+ cell count ratio at Week 24 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+/CD8+ cell count ratio was assessed at Week 24 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [12] 0 0
Baseline and Week 24
Secondary outcome [13] 0 0
Change from Baseline in CD4+/CD8+ cell count ratio at Week 48 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+/CD8+ cell count ratio was assessed at Week 48 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [13] 0 0
Baseline and Week 48
Secondary outcome [14] 0 0
Change from Baseline in CD4+/CD8+ cell count ratio at Week 96 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+/CD8+ cell count ratio was assessed at Week 96 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [14] 0 0
Baseline and Week 96
Secondary outcome [15] 0 0
Change from Baseline in CD4+/CD8+ cell count ratio at Week 144 - Lymphocyte subsets will be collected for assessment by flow cytometry. Change from Baseline in CD4+/CD8+ cell count ratio was assessed at Week 144 to evaluate the immune effects of DTG + 3TC once daily compared to continuation of TBR. Plasma samples for lymphocyte subsets were collected.
Timepoint [15] 0 0
Baseline and Week 144
Secondary outcome [16] 0 0
Number of subjects with HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death through Week 24 - 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.
Timepoint [16] 0 0
Week 24
Secondary outcome [17] 0 0
Number of subjects with HIV-associated conditions, AIDS and death through 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.
Timepoint [17] 0 0
Week 48
Secondary outcome [18] 0 0
Number of subjects with HIV-associated conditions, AIDS and death through Week 96 - 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.
Timepoint [18] 0 0
Week 96
Secondary outcome [19] 0 0
Number of subjects with HIV-associated conditions, AIDS and death through Week 144 - 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.
Timepoint [19] 0 0
Week 144
Secondary outcome [20] 0 0
Number of subjects with any adverse event (AE), serious AE (SAE), SAE and AE leading to discontinuation through 144 weeks - An AE is any untoward medical occurrence in a clinical investigation subject 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 subject or may require medical or surgical intervention. Number of subjects with any AE, SAE, or AE leading to discontinuation through 144 weeks will be summarized.
Timepoint [20] 0 0
Up to Week 144
Secondary outcome [21] 0 0
Number of subjects with laboratory abnormalities through 144 weeks - Blood samples will be collected to evaluate laboratory parameters.
Timepoint [21] 0 0
Up to Week 144
Secondary outcome [22] 0 0
Change from Baseline in total cholesterol at Week 24 - Blood samples will be collected to assess total cholesterol.
Timepoint [22] 0 0
Week 24
Secondary outcome [23] 0 0
Change from Baseline in total cholesterol at Week 48 - Blood samples will be collected to assess total cholesterol.
Timepoint [23] 0 0
Week 48
Secondary outcome [24] 0 0
Change from Baseline in total cholesterol at Week 96 - Blood samples will be collected to assess total cholesterol.
Timepoint [24] 0 0
Week 96
Secondary outcome [25] 0 0
Change from Baseline in total cholesterol at Week 144 - Blood samples will be collected to assess total cholesterol.
Timepoint [25] 0 0
Week 144
Secondary outcome [26] 0 0
Change from Baseline in low density lipoprotein (LDL) cholesterol at Week 24 - Blood samples will be collected to assess LDL cholesterol.
Timepoint [26] 0 0
Week 24
Secondary outcome [27] 0 0
Change from Baseline in LDL cholesterol at Week 48 - Blood samples will be collected to assess LDL cholesterol.
Timepoint [27] 0 0
Week 48
Secondary outcome [28] 0 0
Change from Baseline in LDL cholesterol at Week 96 - Blood samples will be collected to assess LDL cholesterol.
Timepoint [28] 0 0
Week 96
Secondary outcome [29] 0 0
Change from Baseline in LDL cholesterol at Week 144 - Blood samples will be collected to assess LDL cholesterol.
Timepoint [29] 0 0
Week 144
Secondary outcome [30] 0 0
Change from Baseline in high density lipoprotein (HDL) cholesterol at Week 24 - Blood samples will be collected to assess HDL cholesterol.
Timepoint [30] 0 0
Week 24
Secondary outcome [31] 0 0
Change from Baseline in HDL cholesterol at Week 48 - Blood samples will be collected to assess HDL cholesterol.
Timepoint [31] 0 0
Week 48
Secondary outcome [32] 0 0
Change from Baseline in HDL cholesterol at Week 96 - Blood samples will be collected to assess HDL cholesterol.
Timepoint [32] 0 0
Week 96
Secondary outcome [33] 0 0
Change from Baseline in HDL cholesterol at Week 144 - Blood samples will be collected to assess HDL cholesterol.
Timepoint [33] 0 0
Week 144
Secondary outcome [34] 0 0
Change from Baseline in triglycerides at Week 24 - Blood samples will be collected to assess triglycerides.
Timepoint [34] 0 0
Week 24
Secondary outcome [35] 0 0
Change from Baseline in triglycerides at Week 48 - Blood samples will be collected to assess triglycerides.
Timepoint [35] 0 0
Week 48
Secondary outcome [36] 0 0
Change from Baseline in triglycerides at Week 96 - Blood samples will be collected to assess triglycerides.
Timepoint [36] 0 0
Week 96
Secondary outcome [37] 0 0
Change from Baseline in triglycerides at Week 144 - Blood samples will be collected to assess triglycerides.
Timepoint [37] 0 0
Week 144
Secondary outcome [38] 0 0
Number of subjects with observed genotypic and phenotypic resistance to antiretrovirals (ARVs) for subjects meeting Virologic Withdrawal Criteria - Blood samples will be collected for potential viral genotypic and phenotypic analyses to assess viral resistance. Subjects 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.
Timepoint [38] 0 0
Up to Week 144
Secondary outcome [39] 0 0
Change from Baseline in Cystatin C at Week 24 - Blood and urine samples will be collected for Cystatin C.
Timepoint [39] 0 0
Baseline and Week 24
Secondary outcome [40] 0 0
Change from Baseline in Cystatin C at Week 48 - Blood and urine samples will be collected for Cystatin C.
Timepoint [40] 0 0
Baseline and Week 48
Secondary outcome [41] 0 0
Change from Baseline in Cystatin C at Week 96 - Blood and urine samples will be collected for Cystatin C.
Timepoint [41] 0 0
Baseline and Week 96
Secondary outcome [42] 0 0
Change from Baseline in Cystatin C at Week 144 - Blood and urine samples will be collected for Cystatin C.
Timepoint [42] 0 0
Baseline and Week 144
Secondary outcome [43] 0 0
Change from Baseline in Beta-2-Microglobulin at Week 24 - Blood and urine samples will be collected for Beta-2-Microglobulin.
Timepoint [43] 0 0
Baseline and Week 24
Secondary outcome [44] 0 0
Change from Baseline in Beta-2-Microglobulin at Week 48 - Blood and urine samples will be collected for Beta-2-Microglobulin.
Timepoint [44] 0 0
Baseline and Week 48
Secondary outcome [45] 0 0
Change from Baseline in Beta-2-Microglobulin at Week 96 - Blood and urine samples will be collected for Beta-2-Microglobulin.
Timepoint [45] 0 0
Baseline and Week 96
Secondary outcome [46] 0 0
Change from Baseline in Beta-2-Microglobulin at Week 144 - Blood and urine samples will be collected for Beta-2-Microglobulin.
Timepoint [46] 0 0
Baseline and Week 144
Secondary outcome [47] 0 0
Change from Baseline in Retinol Binding Protein at Week 24 - Blood and urine samples will be collected for Retinol Binding Protein.
Timepoint [47] 0 0
Baseline and Week 24
Secondary outcome [48] 0 0
Change from Baseline in Retinol Binding Protein at Week 48 - Blood and urine samples will be collected for Retinol Binding Protein.
Timepoint [48] 0 0
Baseline and Week 48
Secondary outcome [49] 0 0
Change from Baseline in Retinol Binding Protein at Week 96 - Blood and urine samples will be collected for Retinol Binding Protein.
Timepoint [49] 0 0
Baseline and Week 96
Secondary outcome [50] 0 0
Change from Baseline in Retinol Binding Protein at Week 144 - Blood and urine samples will be collected for Retinol Binding Protein.
Timepoint [50] 0 0
Baseline and Week 144
Secondary outcome [51] 0 0
Change from Baseline in bone specific alkaline phosphatase at Weeks 24 - Blood samples will be collected to assess bone specific alkaline phosphatase.
Timepoint [51] 0 0
Baseline and Week 24
Secondary outcome [52] 0 0
Change from Baseline in bone specific alkaline phosphatase at Week 48 - Blood samples will be collected to assess bone specific alkaline phosphatase.
Timepoint [52] 0 0
Baseline and Week 48
Secondary outcome [53] 0 0
Change from Baseline in bone specific alkaline phosphatase at Week 96 - Blood samples will be collected to assess bone specific alkaline phosphatase.
Timepoint [53] 0 0
Baseline and Week 96
Secondary outcome [54] 0 0
Change from Baseline in bone specific alkaline phosphatase at Week 144 - Blood samples will be collected to assess bone specific alkaline phosphatase.
Timepoint [54] 0 0
Baseline and Week 144
Secondary outcome [55] 0 0
Change from Baseline in procollagen type 1-N-propeptide at Week 24 - Blood samples will be collected to assess procollagen type 1-N-propeptide.
Timepoint [55] 0 0
Baseline and Week 24
Secondary outcome [56] 0 0
Change from Baseline in procollagen type 1-N-propeptide at Week 48 - Blood samples will be collected for procollagen type 1-N-propeptide.
Timepoint [56] 0 0
Baseline and Week 48
Secondary outcome [57] 0 0
Change from Baseline in procollagen type 1-N-propeptide at Week 96 - Blood samples will be collected to assess procollagen type 1-N-propeptide.
Timepoint [57] 0 0
Baseline and Week 96
Secondary outcome [58] 0 0
Change from Baseline in procollagen type 1-N-propeptide at Week 144 - Blood samples will be collected to assess procollagen type 1-N-propeptide.
Timepoint [58] 0 0
Baseline and Week 144
Secondary outcome [59] 0 0
Change from Baseline in type 1 collagen cross-linked C-telopeptide at Week 24 - Blood samples will be collected to assess type 1 collagen cross-linked C-telopeptide.
Timepoint [59] 0 0
Baseline and Week 24
Secondary outcome [60] 0 0
Change from Baseline in type 1 collagen cross-linked C-telopeptide at Week 48 - Blood samples will be collected to assess type 1 collagen cross-linked C-telopeptide.
Timepoint [60] 0 0
Baseline and Week 48
Secondary outcome [61] 0 0
Change from Baseline in type 1 collagen cross-linked C-telopeptide at Week 96 - Blood samples will be collected to assess type 1 collagen cross-linked C-telopeptide.
Timepoint [61] 0 0
Baseline and Week 96
Secondary outcome [62] 0 0
Change from Baseline in type 1 collagen cross-linked C-telopeptide at Week 144 - Blood samples will be collected to assess type 1 collagen cross-linked C-telopeptide.
Timepoint [62] 0 0
Baseline and Week 144
Secondary outcome [63] 0 0
Change from Baseline in osteocalcin at Week 24 - Blood samples will be collected for osteocalcin.
Timepoint [63] 0 0
Baseline and Week 24
Secondary outcome [64] 0 0
Change from Baseline in osteocalcin at Week 48 - Blood samples will be collected for osteocalcin.
Timepoint [64] 0 0
Baseline and Week 48
Secondary outcome [65] 0 0
Change from Baseline in osteocalcin at Week 96 - Blood samples will be collected for osteocalcin.
Timepoint [65] 0 0
Baseline and Week 96
Secondary outcome [66] 0 0
Change from Baseline in osteocalcin at Week 144 - Blood samples will be collected for osteocalcin.
Timepoint [66] 0 0
Baseline and Week 144
Secondary outcome [67] 0 0
Change from Baseline in 25 hydroxy-Vitamin D at Week 24 - Blood samples will be collected for 25 hydroxy-Vitamin D.
Timepoint [67] 0 0
Baseline and Week 24
Secondary outcome [68] 0 0
Change from Baseline in 25 hydroxy-Vitamin D at Week 48 - Blood samples will be collected for 25 hydroxy-Vitamin D.
Timepoint [68] 0 0
Baseline and Week 48
Secondary outcome [69] 0 0
Change from Baseline in 25 hydroxy-Vitamin D at Week 96 - Blood samples will be collected for 25 hydroxy-Vitamin D.
Timepoint [69] 0 0
Baseline and Week 96
Secondary outcome [70] 0 0
Change from Baseline in 25 hydroxy-Vitamin D at Week 144 - Blood samples will be collected for 25 hydroxy-Vitamin D.
Timepoint [70] 0 0
Baseline and Week 144
Secondary outcome [71] 0 0
Change from Baseline in health status using European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 24 - The EQ-5D-5L is a standardized, generic questionnaire that provides a profile of subject 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.
Timepoint [71] 0 0
Baseline and Week 24
Secondary outcome [72] 0 0
Change from Baseline in health status using EQ-5D-5L at Week 48 - The EQ-5D-5L is a standardized, generic questionnaire that provides a profile of subject 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 VAS that assesses overall health.
Timepoint [72] 0 0
Baseline and Week 48
Secondary outcome [73] 0 0
Change from Baseline in health status using EQ-5D-5L at Week 96 - The EQ-5D-5L is a standardized, generic questionnaire that provides a profile of subject 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 VAS that assesses overall health.
Timepoint [73] 0 0
Baseline and Week 96
Secondary outcome [74] 0 0
Change from Baseline in health status using EQ-5D-5L at Week 144 - The EQ-5D-5L is a standardized, generic questionnaire that provides a profile of subject 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 VAS that assesses overall health.
Timepoint [74] 0 0
Baseline and Week 144

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
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,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
GSK Investigational Site - Surry Hills
Recruitment hospital [4] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [5] 0 0
GSK Investigational Site - Cairns North
Recruitment hospital [6] 0 0
GSK Investigational Site - Fortitude Valley
Recruitment hospital [7] 0 0
GSK Investigational Site - Highgate Hill
Recruitment hospital [8] 0 0
GSK Investigational Site - Carlton
Recruitment hospital [9] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [10] 0 0
GSK Investigational Site - North Fitzroy
Recruitment hospital [11] 0 0
GSK Investigational Site - Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Surry Hills
Recruitment postcode(s) [4] 0 0
2010 - Sydney
Recruitment postcode(s) [5] 0 0
4870 - Cairns North
Recruitment postcode(s) [6] 0 0
4006 - Fortitude Valley
Recruitment postcode(s) [7] 0 0
4101 - Highgate Hill
Recruitment postcode(s) [8] 0 0
3053 - Carlton
Recruitment postcode(s) [9] 0 0
3168 - Clayton
Recruitment postcode(s) [10] 0 0
3068 - North Fitzroy
Recruitment postcode(s) [11] 0 0
3181 - Prahran
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Hawaii
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Nevada
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oklahoma
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Washington
Country [27] 0 0
Belgium
State/province [27] 0 0
Antwerpen
Country [28] 0 0
Belgium
State/province [28] 0 0
Brussels
Country [29] 0 0
Belgium
State/province [29] 0 0
Brussel
Country [30] 0 0
Belgium
State/province [30] 0 0
Bruxelles
Country [31] 0 0
Belgium
State/province [31] 0 0
Gent
Country [32] 0 0
Belgium
State/province [32] 0 0
Lodelinsart
Country [33] 0 0
Canada
State/province [33] 0 0
British Columbia
Country [34] 0 0
Canada
State/province [34] 0 0
Manitoba
Country [35] 0 0
Canada
State/province [35] 0 0
Ontario
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
Denmark
State/province [37] 0 0
Aalborg
Country [38] 0 0
Denmark
State/province [38] 0 0
Aarhus N
Country [39] 0 0
Denmark
State/province [39] 0 0
Hvidovre
Country [40] 0 0
Denmark
State/province [40] 0 0
Koebenhavn
Country [41] 0 0
Denmark
State/province [41] 0 0
Odense C
Country [42] 0 0
Finland
State/province [42] 0 0
Helsinki
Country [43] 0 0
France
State/province [43] 0 0
Bobigny
Country [44] 0 0
France
State/province [44] 0 0
Bordeaux
Country [45] 0 0
France
State/province [45] 0 0
Creteil
Country [46] 0 0
France
State/province [46] 0 0
Garches
Country [47] 0 0
France
State/province [47] 0 0
Marseille
Country [48] 0 0
France
State/province [48] 0 0
Nice
Country [49] 0 0
France
State/province [49] 0 0
Paris Cedex 10
Country [50] 0 0
France
State/province [50] 0 0
Paris Cedex 13
Country [51] 0 0
France
State/province [51] 0 0
Paris
Country [52] 0 0
France
State/province [52] 0 0
Tourcoing
Country [53] 0 0
Germany
State/province [53] 0 0
Baden-Wuerttemberg
Country [54] 0 0
Germany
State/province [54] 0 0
Bayern
Country [55] 0 0
Germany
State/province [55] 0 0
Hessen
Country [56] 0 0
Germany
State/province [56] 0 0
Niedersachsen
Country [57] 0 0
Germany
State/province [57] 0 0
Nordrhein-Westfalen
Country [58] 0 0
Germany
State/province [58] 0 0
Berlin
Country [59] 0 0
Germany
State/province [59] 0 0
Hamburg
Country [60] 0 0
Germany
State/province [60] 0 0
Koeln
Country [61] 0 0
Germany
State/province [61] 0 0
München
Country [62] 0 0
Italy
State/province [62] 0 0
Emilia-Romagna
Country [63] 0 0
Italy
State/province [63] 0 0
Lazio
Country [64] 0 0
Italy
State/province [64] 0 0
Liguria
Country [65] 0 0
Italy
State/province [65] 0 0
Lombardia
Country [66] 0 0
Italy
State/province [66] 0 0
Piemonte
Country [67] 0 0
Italy
State/province [67] 0 0
Sardegna
Country [68] 0 0
Italy
State/province [68] 0 0
Brescia
Country [69] 0 0
Italy
State/province [69] 0 0
Milano
Country [70] 0 0
Japan
State/province [70] 0 0
Aichi
Country [71] 0 0
Japan
State/province [71] 0 0
Chiba
Country [72] 0 0
Japan
State/province [72] 0 0
Osaka
Country [73] 0 0
Japan
State/province [73] 0 0
Tokyo
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Daegu
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Daejeon
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Gwangju
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Incheon
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Seoul
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Suwon
Country [80] 0 0
Netherlands
State/province [80] 0 0
Rotterdam
Country [81] 0 0
Puerto Rico
State/province [81] 0 0
Ponce
Country [82] 0 0
Puerto Rico
State/province [82] 0 0
San Juan
Country [83] 0 0
Spain
State/province [83] 0 0
Galicia
Country [84] 0 0
Spain
State/province [84] 0 0
Alcala de Henares
Country [85] 0 0
Spain
State/province [85] 0 0
Alicante
Country [86] 0 0
Spain
State/province [86] 0 0
Badalona
Country [87] 0 0
Spain
State/province [87] 0 0
Barcelona
Country [88] 0 0
Spain
State/province [88] 0 0
Cartagena (Murcia)
Country [89] 0 0
Spain
State/province [89] 0 0
Elche
Country [90] 0 0
Spain
State/province [90] 0 0
Granada
Country [91] 0 0
Spain
State/province [91] 0 0
Granollers (Barcelona)
Country [92] 0 0
Spain
State/province [92] 0 0
Huelva
Country [93] 0 0
Spain
State/province [93] 0 0
Lleida
Country [94] 0 0
Spain
State/province [94] 0 0
Madrid
Country [95] 0 0
Spain
State/province [95] 0 0
Majadahonda( Madrid
Country [96] 0 0
Spain
State/province [96] 0 0
Marbella
Country [97] 0 0
Spain
State/province [97] 0 0
Mataró
Country [98] 0 0
Spain
State/province [98] 0 0
Murcia
Country [99] 0 0
Spain
State/province [99] 0 0
Málaga
Country [100] 0 0
Spain
State/province [100] 0 0
Santiago de Compostela
Country [101] 0 0
Spain
State/province [101] 0 0
Sevilla
Country [102] 0 0
Spain
State/province [102] 0 0
Valencia
Country [103] 0 0
Spain
State/province [103] 0 0
Vilajoyosa
Country [104] 0 0
Spain
State/province [104] 0 0
Zaragoza
Country [105] 0 0
Sweden
State/province [105] 0 0
Göteborg
Country [106] 0 0
Sweden
State/province [106] 0 0
Malmö
Country [107] 0 0
Sweden
State/province [107] 0 0
Stockholm
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Berkshire
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Midlothian
Country [110] 0 0
United Kingdom
State/province [110] 0 0
West Midlands
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Yorkshire
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Birmingham
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Brighton
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Bristol
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Crumpsall, Manchester
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Hull
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Liverpool
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Sheffield
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Tooting, London

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
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03446573
Trial related presentations / publications
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
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable