Clinical trial NCT04900038: A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults
Official title: A 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Human immunodeficiency virus-1
GSK3640254
Dolutegravir
Lamivudine
Treatment-naive
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2021-05-25
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, parallel-group study.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24
timeFrame: At Week 24
Secondary outcomes:
measure: Absolute Values of HIV-1 RNA Through Week 24
timeFrame: At Baseline (Day 1) and Week 24
measure: Change From Baseline in HIV-1 RNA Through Week 24
timeFrame: At Week 24 compared to baseline (Day 1)
measure: Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24
timeFrame: At Baseline (Day 1) and Week 24
measure: Change From Baseline in CD4+ T-cell Counts Through Week 24
timeFrame: At Week 24 compared to baseline (Day 1)
measure: Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478)
timeFrame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
measure: Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478)
timeFrame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
measure: Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478)
timeFrame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
measure: Number of Participants Who Develop Genotypic Resistance up to Week 24
timeFrame: From Day 1 up to Week 24
measure: Number of Participants Who Develop Phenotypic Resistance up to Week 24
timeFrame: From Day 1 up to Week 24
measure: Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24
timeFrame: At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE)
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Palm Springs
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Paris
country: France
facility: GSK Investigational Site
city: Tourcoing cedex
country: France
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Bergamo
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Vila Nova de Gaia
country: Portugal
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Parow
country: South Africa
facility: GSK Investigational Site
city: Vosloorus Ext 2
country: South Africa
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: Elche
country: Spain
facility: GSK Investigational Site
city: La Laguna-Tenerife
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Sant Boi de Llobregat
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vigo
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: