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    Clinical Trial Results:
    Phase IIb, randomized, double-blind, parallel-group study to assess the efficacy, safety, tolerability, and resistance profile of GSK3640254 in combination with dolutegravir compared to dolutegravir plus lamivudine in HIV-1 infected, treatment naïve adults

    Summary
    EudraCT number
    		 2021-000016-28
    Trial protocol
    		 FR   DE   PT   ES   IT  
    Global end of trial date
    11 May 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Feb 2024
    First version publication date
    16 Feb 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    212483
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ViiV Healthcare
    Sponsor organisation address
    980 GreatWest Road, Brentford,Middlesex, United Kingdom, TW8 9GS
    Public contact
    ViiV Healthcare, GSK Response Center, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Jul 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 May 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate antiviral efficacy of GSK3640254 (all concentrations)+ DTG, relative to DTG+3TC at week 24 in HIV-1 infected ART (anti-retroviral therapy) naive participants.
    Protection of trial subjects
    Not applicable.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Aug 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 8
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Puerto Rico: 8
    Country: Number of subjects enrolled
    South Africa: 7
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    United States: 10
    Worldwide total number of subjects
    85
    EEA total number of subjects
    50
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    85
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study assessed efficacy, safety and resistance of GSK3640254 in combination with dolutegravir (DTG) compared to DTG+lamivudine in HIV-1 infected treatment-naïve adults. Study was terminated after primary analysis as the sponsor determined further development of study regimen would not be differentiated enough from existing similar regimens.

    Pre-assignment
    Screening details
    		 The changes from the planned subsequent analyses were presented as pre-specified in Statistical Analysis Plan. Secondary analyses at week 48 were not evaluated. Safety analysis is presented based on the Entire Duration of Treatment Exposure period, defined as from Day 1 up to end of continued access to treatment post-study termination (Day 478).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg
    Arm description
    		 Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir (50 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 50 mg tablet administered daily via oral administration

    Investigational medicinal product name
    GSK3640254 (100 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One or more tablets (equivalent of 100 mg product) administered daily via oral administration

    Arm title
    		 GSK3640254 150 mg + DTG 50 mg
    Arm description
    		 Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir (50 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 50 mg tablet administered daily via oral administration

    Investigational medicinal product name
    GSK3640254 (150 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One or more tablets (equivalent of 150 mg product) administered daily via oral administration

    Arm title
    		 GSK3640254 200 mg + DTG 50 mg
    Arm description
    		 Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir (50 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 50 mg tablet administered daily via oral administration

    Investigational medicinal product name
    GSK3640254 (200 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One or more tablets (equivalent of 200 mg product) administered daily via oral administration

    Arm title
    		 DTG 50 mg + Lamivudine (3TC) 300 mg
    Arm description
    		 Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Lamivudine (300 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    One 300 mg capsule administered daily via oral administration

    Investigational medicinal product name
    Dolutegravir (50 mg)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 50 mg tablet administered daily via oral administration

    Number of subjects in period 1
    		GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Started
    22
    20
    22
    21
    Completed
    2
    3
    2
    3
    Not completed
    20
    17
    20
    18
         Consent withdrawn by subject
    -
    1
    -
    -
         Protocol-defined stoping criteria reached
    -
    -
    2
    2
         Adverse event, non-fatal
    1
    -
    1
    1
         Protocol Deviation
    1
    1
    -
    -
         Study terminated by sponsor
    18
    15
    17
    14
         Lost to follow-up
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK3640254 100 mg + Dolutegravir (DTG) 50 mg
    Reporting group description
    		 Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    GSK3640254 150 mg + DTG 50 mg
    Reporting group description
    		 Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    GSK3640254 200 mg + DTG 50 mg
    Reporting group description
    		 Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    DTG 50 mg + Lamivudine (3TC) 300 mg
    Reporting group description
    		 Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.

    Reporting group values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg Total
    Number of subjects
    		 22 20 22 21 85
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 22 20 22 21 85
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 34.2 ( 7.53 ) 36.9 ( 10.51 ) 32.6 ( 8.41 ) 32.1 ( 8.62 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 3 4 5 3 15
        Male
    		 19 16 17 18 70
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 0 0 0 1 1
        Black or African American
    		 3 4 3 3 13
        White
    		 18 14 16 14 62
        Mixed Race
    		 0 1 1 0 2
        Other - Unspecified
    		 1 1 2 3 7

    End points

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    End points reporting groups
    Reporting group title
    GSK3640254 100 mg + Dolutegravir (DTG) 50 mg
    Reporting group description
    		 Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    GSK3640254 150 mg + DTG 50 mg
    Reporting group description
    		 Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    GSK3640254 200 mg + DTG 50 mg
    Reporting group description
    		 Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    DTG 50 mg + Lamivudine (3TC) 300 mg
    Reporting group description
    		 Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.

    Primary: Percentage of participants with plasma HIV-1 ribonucleic acid (RNA) less than (<)50 copies per milliliter (c/mL) at Week 24

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    End point title
    		 Percentage of participants with plasma HIV-1 ribonucleic acid (RNA) less than (<)50 copies per milliliter (c/mL) at Week 24 [1]
    End point description
    Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity in HIV-1 infected ART (anti-retroviral therapy)-naïve participants. Analysis was performed on Intent-to-Treat Exposed (ITT-E) Population included all randomized participants who received at least one dose of study intervention and had data for plasma HIV-1 RNA <50 c/mL as per timeline assessed.
    End point type
    Primary
    End point timeframe
    At Week 24
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analysis was performed.
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: Percentage of participants
    95
    85
    77
    86
    No statistical analyses for this end point

    Secondary: Absolute values of HIV-1 RNA through Week 24

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    End point title
    		 Absolute values of HIV-1 RNA through Week 24
    End point description
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log 10) values for plasma HIV-1 RNA has been presented. Baseline is defined as the latest non-missing value prior to first dose of treatment according to date and time including unscheduled visits. Analysis was performed on ITT-E Population that had data for absolute values of HIV-1 RNA as per timeline assessed.
    End point type
    Secondary
    End point timeframe
    At Baseline (Day 1) and Week 24
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: log10 copies per milliliter(log10 c/mL)
    arithmetic mean (standard deviation)
        Baseline (Day 1) (N=22,20,22,21)
    4.614 ( 0.5253 )
    4.446 ( 0.5913 )
    4.535 ( 0.4165 )
    4.179 ( 0.5907 )
        Week 24 (N=21,19,20,19)
    1.315 ( 0.0737 )
    1.532 ( 0.7086 )
    1.349 ( 0.1431 )
    1.379 ( 0.2439 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in HIV-1 RNA through Week 24

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    End point title
    		 Change from Baseline in HIV-1 RNA through Week 24
    End point description
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log 10) values for plasma HIV-1 RNA has been presented. Change from Baseline is defined as post-dose visit value minus Baseline value. Analysis was performed on ITT-E Population that had data for absolute values of HIV-1 RNA as per timeline assessed.
    End point type
    Secondary
    End point timeframe
    At Week 24 compared to baseline (Day 1)
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    20
    19
    Units: log10 c/mL
        arithmetic mean (standard deviation)
    -3.306 ( 0.5163 )
    -2.874 ( 0.8476 )
    -3.186 ( 0.4809 )
    -2.767 ( 0.5531 )
    No statistical analyses for this end point

    Secondary: Absolute values of cluster of differentiation 4+ (CD4+) T-cell counts through Week 24

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    End point title
    		 Absolute values of cluster of differentiation 4+ (CD4+) T-cell counts through Week 24
    End point description
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity. Baseline is defined as the latest non-missing value prior to first dose of treatment according to date and time including unscheduled visits. Analysis was performed on ITT-E Population that had data for CD4+ T-cells analysis as per timeline assessed.
    End point type
    Secondary
    End point timeframe
    At Baseline (Day 1) and Week 24
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: cells per cubic millimeter (cells/mm^3)
    arithmetic mean (standard deviation)
        Baseline (Day 1) (N=22,20,22,21)
    436.7 ( 161.93 )
    451.4 ( 164.86 )
    534.8 ( 200.99 )
    506.9 ( 165.14 )
        Week 24 (N=22,20,19,21)
    753.4 ( 222.73 )
    661.0 ( 193.50 )
    756.1 ( 267.69 )
    627.5 ( 175.94 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in CD4+ T-cell counts through Week 24

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    End point title
    		 Change from Baseline in CD4+ T-cell counts through Week 24
    End point description
    Blood samples were collected and CD4+ cell count assessment was carried out to evaluate the immunologic activity. Change from Baseline is defined as post-dose visit value minus Baseline value. Analysis was performed on ITT-E Population that had data for CD4+ T-cells analysis as per timeline assessed.
    End point type
    Secondary
    End point timeframe
    At Week 24 compared to baseline (Day 1)
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    21
    19
    19
    19
    Units: cells/mm^3
        arithmetic mean (standard deviation)
    317.7 ( 175.42 )
    200.6 ( 126.68 )
    241.2 ( 168.83 )
    139.5 ( 126.63 )
    No statistical analyses for this end point

    Secondary: Number of participants with serious adverse events (SAEs) and deaths, up to end of continued access to treatment post-study termination (Day 478)

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    End point title
    		 Number of participants with serious adverse events (SAEs) and deaths, up to end of continued access to treatment post-study termination (Day 478)
    End point description
    An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478). Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to end of continued access to treatment post-study termination (Day 478)
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: Participants
        SAEs
    2
    0
    0
    1
        Death
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants with adverse events (AEs) leading to discontinuation, up to end of continued access to treatment post-study termination (Day 478)

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    End point title
    		 Number of participants with adverse events (AEs) leading to discontinuation, up to end of continued access to treatment post-study termination (Day 478)
    End point description
    Number of participants who discontinued treatment due to AEs are presented. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478). Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to end of continued access to treatment post-study termination (Day 478)
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: Participants
    1
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Number of participants with adverse events of special interest (AESIs), up to end of continued access to treatment post-study termination (Day 478)

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    End point title
    		 Number of participants with adverse events of special interest (AESIs), up to end of continued access to treatment post-study termination (Day 478)
    End point description
    AEs of special interest (AESIs) included AEs related to QT prolongation, gastrointestinal (GI) intolerability/toxicity, psychiatric events, nervous system disorders, skin and subcutaneous tissue disorders and cardiac disorders. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478). Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to end of continued access to treatment post-study termination (Day 478)
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: Participants
        AEs related to QT prolongation
    0
    0
    0
    0
        AEs related to GI intolerability/toxicity
    5
    7
    8
    5
        AEs related to psychiatric events
    0
    3
    0
    4
        AEs related to nervous system disorders
    2
    4
    5
    2
        AEs related to skin, subcutaneous tissue disorder
    4
    0
    4
    0
        AEs related to cardiac disorders
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants who develop phenotypic resistance up to Week 24

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    End point title
    		 Number of participants who develop phenotypic resistance up to Week 24
    End point description
    Blood samples were collected for drug resistance testing to assess the development of viral resistance to GSK3640254 and other on-study Anti-Retroviral Therapy (ART) in participants experiencing virologic failure through Week 24. Only plasma HIV-1 RNA values determined by the central laboratory were used to assess virologic failure. PDVF was defined as having virologic non-response (HIV-1 RNA <1.0 log10 c/mL reduction from baseline and <200 copies/mL by Week 12, confirmed levels >=200 c/mL at or after Week 24 and plasma HIV-1 RNA <= 50 c/mL from testing on Week 24, virologic rebound (confirmed HIV-1 RNA >=200 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL). Analysis was performed on ITT-E population.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to Week 24
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants who develop genotypic resistance up to Week 24

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    End point title
    		 Number of participants who develop genotypic resistance up to Week 24
    End point description
    Blood samples were collected for drug resistance testing to assess the development of viral resistance to GSK3640254 through Week 24. New mutations were tabulated by drug class: integrase strand transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI). Protocol-Defined Virologic Failure (PDVF) was defined as having virologic non-response (HIV-1 RNA <1.0 log10 c/mL reduction from baseline and <200 copies/mL by Week 12, confirmed levels >=200 c/mL at or after Week 24 and plasma HIV-1 RNA <= 50 c/mL from testing on Week 24, virologic rebound (confirmed HIV-1 RNA >=200 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL). Analysis was performed on ITT-E population.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to Week 24
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Number of subjects analysed
    22
    20
    22
    21
    Units: Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Trough concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24

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    End point title
    		 Trough concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 [2]
    End point description
    Trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. This was determined to assess the steady-state exposure of GSK3640254 when given in combination with DTG. Analysis performed on Pharmacokinetic population, which included all participants who received GSK3640254, underwent sparse PK sampling during the study, and provided evaluable GSK3640254 plasma concentration data, demographic and baseline characteristics, and/or information on concomitant medications. Only those participants with data available at specified time points were analyzed for the specific category titles.
    End point type
    Secondary
    End point timeframe
    At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE)
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint presented the Ctrough analysis only for the arms that received one of the GSK3640254 doses (administered along with DTG), hence the DTG 50 mg + Lamivudine (3TC) 300 mg arm was not included in this endpoint.
    End point values
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg
    Number of subjects analysed
    22
    20
    22
    Units: nanogram per milliliter (ng/mL)
    geometric mean (confidence interval 95%)
        Week 2 (N=21,19,22)
    340.2 (269.5 to 411.0)
    549.9 (390.9 to 708.9)
    724.2 (563.4 to 885.0)
        Week 4 (N=21,20,21)
    417.8 (330.5 to 505.0)
    632.7 (470.4 to 795.0)
    799.6 (640.9 to 958.3)
        Week 8 (N=22,20,22)
    386.2 (293.7 to 478.6)
    646.6 (421.7 to 871.5)
    821.1 (620.2 to 1022.0)
        Week 12 (PRE DOSE) (N=22,20,22)
    481.3 (388.6 to 574.0)
    611.4 (430.6 to 792.1)
    877.2 (704.1 to 1050.3)
        Week 12 (2-6HR POST DOSE) (N=21,20,21)
    767.8 (612.3 to 923.3)
    1081.2 (759.5 to 1402.8)
    1658.1 (1305.8 to 2010.4)
        Week 24 (PRE DOSE) (N=21,19,19)
    396.0 (331.0 to 460.8)
    570.1 (333.6 to 806.6)
    848.8 (600.3 to 1097.4)
        Week 24 (2-6HR POST DOSE) (N=20,20,19)
    759.0 (623.1 to 894.8)
    1107.0 (660.8 to 1553.2)
    1584.1 (1067.3 to 2100.9)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478).
    Adverse event reporting additional description
    The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v26.0
    Reporting groups
    Reporting group title
    GSK3640254 100 mg + Dolutegravir (DTG) 50 mg
    Reporting group description
    		 Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    GSK3640254 150 mg + DTG 50 mg
    Reporting group description
    		 Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    GSK3640254 200 mg + DTG 50 mg
    Reporting group description
    		 Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.

    Reporting group title
    DTG 50 mg + Lamivudine (3TC) 300 mg
    Reporting group description
    		 Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.

    Serious adverse events
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Nervous system disorders
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anogenital dysplasia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 GSK3640254 100 mg + Dolutegravir (DTG) 50 mg GSK3640254 150 mg + DTG 50 mg GSK3640254 200 mg + DTG 50 mg DTG 50 mg + Lamivudine (3TC) 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 22 (72.73%)
    15 / 20 (75.00%)
    17 / 22 (77.27%)
    14 / 21 (66.67%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anogenital warts
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Investigations
    Blood pressure increased
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    2
    1
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Headache
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 20 (15.00%)
    3 / 22 (13.64%)
    2 / 21 (9.52%)
         occurrences all number
    2
    4
    3
    5
    Sciatica
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 20 (10.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    0
    1
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 20 (10.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    2
    2
    1
    1
    Fatigue
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 20 (15.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    0
    1
    Toothache
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 20 (10.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    0
    1
    Nausea
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    2 / 21 (9.52%)
         occurrences all number
    1
    1
    1
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    0
    1
    Faeces soft
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Dyspepsia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    2
    Diarrhoea
         subjects affected / exposed
    1 / 22 (4.55%)
    4 / 20 (20.00%)
    5 / 22 (22.73%)
    2 / 21 (9.52%)
         occurrences all number
    2
    6
    6
    2
    Abdominal pain upper
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 20 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Reproductive system and breast disorders
    Vascular disorders Hypertension
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    1
    Erectile dysfunction
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Cough
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 20 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Catarrh
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Skin lesion
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    0
    1
    Rash
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 20 (0.00%)
    3 / 22 (13.64%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    3
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 20 (10.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    0
    1
    Musculoskeletal and connective tissue disorders
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Back pain
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 20 (10.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    2
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 20 (10.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Infections and infestations
    Folliculitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    1
    Urethritis chlamydial
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    0
    1
    COVID-19
         subjects affected / exposed
    3 / 22 (13.64%)
    2 / 20 (10.00%)
    5 / 22 (22.73%)
    3 / 21 (14.29%)
         occurrences all number
    3
    2
    5
    3
    Herpes simplex
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Influenza
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    0
    3
    Monkeypox
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    3 / 22 (13.64%)
    3 / 21 (14.29%)
         occurrences all number
    1
    1
    5
    3
    Oropharyngeal gonococcal infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    1
    1
    Pharyngeal chlamydia infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    2 / 22 (9.09%)
    0 / 21 (0.00%)
         occurrences all number
    1
    2
    2
    0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    1
    Respiratory tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 20 (5.00%)
    2 / 22 (9.09%)
    3 / 21 (14.29%)
         occurrences all number
    2
    1
    2
    6
    Conjunctivitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    1
    1
    Viral infection
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Gastroeneteritis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 20 (5.00%)
    2 / 22 (9.09%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Sep 2022
    The changes in this amendments were the reduction of the sample size of the participants and adjustment of number of participants among the 3 experimental arms.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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