A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults (DYNAMIC)

ViiV Healthcare

Status and phase: Terminated; Phase 2

Conditions: HIV Infections

Treatments: Drug: GSK3640254; Drug: Dolutegravir; Drug: Lamivudine capsules; Drug: Lamivudine tablets

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04900038

212483

Details and patient eligibility

About

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.

Enrollment: 85 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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85 participants in 4 patient groups

GSK3640254 100 mg + Dolutegravir (DTG) 50 mg

Experimental 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.

Treatment:

Drug: Dolutegravir

Drug: GSK3640254

GSK3640254 150 mg + DTG 50 mg

Experimental 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.

Treatment:

Drug: Dolutegravir

Drug: GSK3640254

GSK3640254 200 mg + DTG 50 mg

Experimental 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.

Treatment:

Drug: Dolutegravir

Drug: GSK3640254

DTG 50 mg + Lamivudine (3TC) 300 mg

Active Comparator 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.

Treatment:

Drug: Lamivudine capsules

Drug: Dolutegravir

Drug: Lamivudine tablets