HIV Infections
Conditions
Keywords
Human immunodeficiency virus-1, GSK3640254, Dolutegravir, Lamivudine, Treatment-naive
Brief summary
The purpose of this study was to evaluate the efficacy of GSK3640254 + DTG relative to lamivudine (3TC) + DTG in treatment-naïve adult participants living with human immunodeficiency virus (HIV)-1. The participants were randomized to one of the three doses of blinded GSK3640254 (100, 150, or 200 milligrams \[mgs\]) or a reference arm of blinded 3TC-each in combination with open label DTG.
Interventions
DRUGGSK3640254
GSK3640254 was available as 25 mg or 100 mg tablets administered orally.
DRUGDolutegravir
DTG was available as 50 mg tablets administered orally.
DRUGLamivudine capsules
3TC was available as 300 mg capsules administered orally as a blinded treatment.
DRUGLamivudine tablets
3TC was available as 300 mg tablets administered orally as an unblinded treatment.
Sponsors
Syneos Health
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The dose level of GSK3640254 in each of the treatment arms containing GSK3640254 was blinded to the research participants and all study personnel during the study through the Week 24 primary endpoint.
Intervention model description
This is a randomized, parallel-group study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy) received after a known diagnosis of HIV-1 infection. * Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (\>=)1000 c/mL. * Screening CD4+ T-cell count \>=250 cells per millimeter\^3 (cells/cubic millimeter). * Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs.\]) for men and \>=45.0 kg (99 lbs.) for women and body mass index (BMI) \>18.5 kilograms per meter\^2 (kg/meter square). Calculations will utilize sex assigned at birth.
Exclusion criteria
* 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. * Presence of primary HIV infection, evidenced by acute retroviral syndrome (example \[e.g.\], fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion. * Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment); * History of ongoing or clinically relevant hepatitis within the previous 6 months. * Any history of significant underlying psychiatric disorder. * Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment. * A pre-existing condition, in the opinion of the Investigator or Medical Monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease \[GERD\], gastric ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, or with the absorption, metabolism, and/or excretion of the study interventions or render the participant unable to take oral study treatment. * Familial or personal history of long QT syndrome or sudden cardiac death. * Active treatment for a viral infection other than HIV-1, such as Hepatitis B, with an agent that is active against HIV-1 (were known to be infected with HIV-1 after treatment for Hepatitis B was completed). * Participants who require concomitant medications known to be associated with a prolonged corrected QT (QTc) interval. * Exposure to an experimental drug, human blood product, monoclonal antibody, or vaccine (which does not have emergency, conditional, or standard market authorization) within 28 days prior to the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | At Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HIV-1 RNA Through Week 24 | At Week 24 compared to baseline (Day 1) | 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. |
| Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | At Baseline (Day 1) and Week 24 | 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. |
| Change From Baseline in CD4+ T-cell Counts Through Week 24 | At Week 24 compared to baseline (Day 1) | 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. |
| Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | From Day 1 up to end of continued access to treatment post-study termination (Day 478) | 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). |
| Absolute Values of HIV-1 RNA Through Week 24 | At Baseline (Day 1) and Week 24 | 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. |
| Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | From Day 1 up to end of continued access to treatment post-study termination (Day 478) | 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). |
| Number of Participants Who Develop Genotypic Resistance up to Week 24 | From Day 1 up to Week 24 | 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). |
| Number of Participants Who Develop Phenotypic Resistance up to Week 24 | From Day 1 up to Week 24 | 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). |
| Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE) | 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. |
| Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478) | From Day 1 up to end of continued access to treatment post-study termination (Day 478) | 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). |
Countries
Argentina, Canada, France, Germany, Italy, Portugal, Puerto Rico, South Africa, Spain, United States
Participant flow
Recruitment details
This study assessed efficacy, safety and resistance of GSK3640254 in combination with dolutegravir compared to dolutegravir + lamivudine in HIV-1 infected, treatment-naïve adults. The study was terminated by the sponsor after primary analysis (at week 24) as the sponsor determined further development of GSK3640254-containing daily oral regimen would not be differentiated enough from existing 2-drug daily oral regimens. Thus, secondary analyses at week 48 were not evaluated.
Pre-assignment details
The changes from the planned subsequent analyses were presented as pre-specified in Statistical Analysis Plan. Safety analysis is presented based on the Entire Duration of Treatment Exposure period, which is defined from Day 1 up to end of continued access to treatment post-study termination (Day 478).
Participants by arm
| Arm | Count |
|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg 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. | 22 |
| GSK3640254 150 mg + DTG 50 mg 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. | 20 |
| GSK3640254 200 mg + DTG 50 mg 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. | 22 |
| DTG 50 mg + Lamivudine (3TC) 300 mg 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. | 21 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Participant reached protocol-defined stoping criteria | 0 | 0 | 2 | 2 |
| Overall Study | Protocol Deviation | 1 | 1 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 18 | 15 | 17 | 14 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|
| Age, Continuous | 34.2 Years STANDARD_DEVIATION 7.53 | 36.9 Years STANDARD_DEVIATION 10.51 | 32.6 Years STANDARD_DEVIATION 8.41 | 32.1 Years STANDARD_DEVIATION 8.62 | 33.9 Years STANDARD_DEVIATION 8.83 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 13 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other - Unspecified | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 14 Participants | 16 Participants | 14 Participants | 62 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 5 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 19 Participants | 16 Participants | 17 Participants | 18 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 | 0 / 22 | 0 / 21 |
| other Total, other adverse events | 16 / 22 | 15 / 20 | 17 / 22 | 14 / 21 |
| serious Total, serious adverse events | 2 / 22 | 0 / 20 | 0 / 22 | 1 / 21 |
Outcome results
Primary
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24
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.
Time frame: At Week 24
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 95 Percentage of participants |
| GSK3640254 150 mg + DTG 50 mg | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 85 Percentage of participants |
| GSK3640254 200 mg + DTG 50 mg | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 77 Percentage of participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 86 Percentage of participants |
Secondary
Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24
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.
Time frame: At Baseline (Day 1) and Week 24
Population: Analysis was performed on ITT-E Population that had data for CD4+ T-cells analysis as per timeline assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Baseline (Day 1) | 436.7 cells per cubic millimeter (cells/mm^3) | Standard Deviation 161.93 |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Week 24 | 753.4 cells per cubic millimeter (cells/mm^3) | Standard Deviation 222.73 |
| GSK3640254 150 mg + DTG 50 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Week 24 | 661.0 cells per cubic millimeter (cells/mm^3) | Standard Deviation 193.5 |
| GSK3640254 150 mg + DTG 50 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Baseline (Day 1) | 451.4 cells per cubic millimeter (cells/mm^3) | Standard Deviation 164.86 |
| GSK3640254 200 mg + DTG 50 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Week 24 | 756.1 cells per cubic millimeter (cells/mm^3) | Standard Deviation 267.69 |
| GSK3640254 200 mg + DTG 50 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Baseline (Day 1) | 534.8 cells per cubic millimeter (cells/mm^3) | Standard Deviation 200.99 |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Week 24 | 627.5 cells per cubic millimeter (cells/mm^3) | Standard Deviation 175.94 |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 | Baseline (Day 1) | 506.9 cells per cubic millimeter (cells/mm^3) | Standard Deviation 165.14 |
Secondary
Absolute Values of HIV-1 RNA Through Week 24
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.
Time frame: At Baseline (Day 1) and Week 24
Population: Analysis was performed on ITT-E Population that had data for absolute values of HIV-1 RNA as per timeline assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Absolute Values of HIV-1 RNA Through Week 24 | Baseline (Day 1) | 4.614 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.5253 |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Absolute Values of HIV-1 RNA Through Week 24 | Week 24 | 1.315 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.0737 |
| GSK3640254 150 mg + DTG 50 mg | Absolute Values of HIV-1 RNA Through Week 24 | Week 24 | 1.532 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.7086 |
| GSK3640254 150 mg + DTG 50 mg | Absolute Values of HIV-1 RNA Through Week 24 | Baseline (Day 1) | 4.446 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.5913 |
| GSK3640254 200 mg + DTG 50 mg | Absolute Values of HIV-1 RNA Through Week 24 | Baseline (Day 1) | 4.535 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.4165 |
| GSK3640254 200 mg + DTG 50 mg | Absolute Values of HIV-1 RNA Through Week 24 | Week 24 | 1.349 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.1431 |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Absolute Values of HIV-1 RNA Through Week 24 | Baseline (Day 1) | 4.179 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.5907 |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Absolute Values of HIV-1 RNA Through Week 24 | Week 24 | 1.379 log10 copies per milliliter(log10 c/mL) | Standard Deviation 0.2439 |
Secondary
Change From Baseline in CD4+ T-cell Counts Through Week 24
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.
Time frame: At Week 24 compared to baseline (Day 1)
Population: Analysis was performed on ITT-E Population that had data for CD4+ T-cells analysis as per timeline assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Change From Baseline in CD4+ T-cell Counts Through Week 24 | 317.7 cells/mm^3 | Standard Deviation 175.42 |
| GSK3640254 150 mg + DTG 50 mg | Change From Baseline in CD4+ T-cell Counts Through Week 24 | 200.6 cells/mm^3 | Standard Deviation 126.68 |
| GSK3640254 200 mg + DTG 50 mg | Change From Baseline in CD4+ T-cell Counts Through Week 24 | 241.2 cells/mm^3 | Standard Deviation 168.83 |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Change From Baseline in CD4+ T-cell Counts Through Week 24 | 139.5 cells/mm^3 | Standard Deviation 126.63 |
Secondary
Change From Baseline in HIV-1 RNA Through Week 24
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.
Time frame: At Week 24 compared to baseline (Day 1)
Population: Analysis was performed on ITT-E Population that had data for absolute values of HIV-1 RNA as per timeline assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Change From Baseline in HIV-1 RNA Through Week 24 | -3.306 log10 c/mL | Standard Deviation 0.5163 |
| GSK3640254 150 mg + DTG 50 mg | Change From Baseline in HIV-1 RNA Through Week 24 | -2.874 log10 c/mL | Standard Deviation 0.8476 |
| GSK3640254 200 mg + DTG 50 mg | Change From Baseline in HIV-1 RNA Through Week 24 | -3.186 log10 c/mL | Standard Deviation 0.4809 |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Change From Baseline in HIV-1 RNA Through Week 24 | -2.767 log10 c/mL | Standard Deviation 0.5531 |
Secondary
Number of Participants Who Develop Genotypic Resistance up to Week 24
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).
Time frame: From Day 1 up to Week 24
Population: Analysis was performed on ITT-E population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants Who Develop Genotypic Resistance up to Week 24 | 0 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants Who Develop Genotypic Resistance up to Week 24 | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants Who Develop Genotypic Resistance up to Week 24 | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants Who Develop Genotypic Resistance up to Week 24 | 0 Participants |
Secondary
Number of Participants Who Develop Phenotypic Resistance up to Week 24
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).
Time frame: From Day 1 up to Week 24
Population: Analysis was performed on ITT-E Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants Who Develop Phenotypic Resistance up to Week 24 | 0 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants Who Develop Phenotypic Resistance up to Week 24 | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants Who Develop Phenotypic Resistance up to Week 24 | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants Who Develop Phenotypic Resistance up to Week 24 | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478)
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).
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
Population: Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478) | 1 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478) | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478) | 1 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478) | 0 Participants |
Secondary
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478)
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).
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
Population: Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to QT prolongation | 0 Participants |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to GI intolerability/toxicity | 5 Participants |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to psychiatric events | 0 Participants |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to nervous system disorders | 2 Participants |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to skin and subcutaneous tissue disorder | 4 Participants |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to cardiac disorders | 1 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to cardiac disorders | 0 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to nervous system disorders | 4 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to QT prolongation | 0 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to psychiatric events | 3 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to GI intolerability/toxicity | 7 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to skin and subcutaneous tissue disorder | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to GI intolerability/toxicity | 8 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to psychiatric events | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to nervous system disorders | 5 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to cardiac disorders | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to skin and subcutaneous tissue disorder | 4 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to QT prolongation | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to skin and subcutaneous tissue disorder | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to cardiac disorders | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to GI intolerability/toxicity | 5 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to nervous system disorders | 2 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to QT prolongation | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) | AEs related to psychiatric events | 4 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478)
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).
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
Population: Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | SAEs | 2 Participants |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | Death | 0 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | Death | 0 Participants |
| GSK3640254 150 mg + DTG 50 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | SAEs | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | SAEs | 0 Participants |
| GSK3640254 200 mg + DTG 50 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | Death | 0 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | SAEs | 1 Participants |
| DTG 50 mg + Lamivudine (3TC) 300 mg | Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) | Death | 0 Participants |
Secondary
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24
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.
Time frame: At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 4 | 417.8 nanogram per milliliter (ng/mL) |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 12 (2-6HR POST DOSE) | 767.8 nanogram per milliliter (ng/mL) |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 12 ( PRE DOSE) | 481.3 nanogram per milliliter (ng/mL) |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 2 | 340.2 nanogram per milliliter (ng/mL) |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 24 (2-6HR POST DOSE) | 759.0 nanogram per milliliter (ng/mL) |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 24 ( PRE DOSE) | 396.0 nanogram per milliliter (ng/mL) |
| GSK3640254 100 mg + Dolutegravir (DTG) 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 8 | 386.2 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 12 ( PRE DOSE) | 611.4 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 2 | 549.9 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 4 | 632.7 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 8 | 646.6 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 12 (2-6HR POST DOSE) | 1081.2 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 24 ( PRE DOSE) | 570.1 nanogram per milliliter (ng/mL) |
| GSK3640254 150 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 24 (2-6HR POST DOSE) | 1107.0 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 12 (2-6HR POST DOSE) | 1658.1 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 4 | 799.6 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 24 (2-6HR POST DOSE) | 1584.1 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 24 ( PRE DOSE) | 848.8 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 12 ( PRE DOSE) | 877.2 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 8 | 821.1 nanogram per milliliter (ng/mL) |
| GSK3640254 200 mg + DTG 50 mg | Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 | Week 2 | 724.2 nanogram per milliliter (ng/mL) |