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

NCT04900038 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 212483
• Study Type: interventional
• Target: 85
• Locations: 10 countries
• Sites: 44

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.

Conditions

HIV Infections

Keywords

Human immunodeficiency virus-1; GSK3640254; Dolutegravir; Lamivudine; Treatment-naive

Outcome Measures

Primary Outcomes (1)

• 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.

  At Week 24

Secondary Outcomes (10)

• Absolute Values of HIV-1 RNA Through Week 24

  At Baseline (Day 1) and Week 24

• Change From Baseline in HIV-1 RNA Through Week 24

  At Week 24 compared to baseline (Day 1)

• Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24

  At Baseline (Day 1) and Week 24

• Change From Baseline in CD4+ T-cell Counts Through Week 24

  At Week 24 compared to baseline (Day 1)

• 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)

Study Arms (4)

GSK3640254 100 mg + Dolutegravir (DTG) 50 mg

EXPERIMENTAL

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.

Drug: GSK3640254; Drug: Dolutegravir

GSK3640254 150 mg + DTG 50 mg

EXPERIMENTAL

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.

Drug: GSK3640254; Drug: Dolutegravir

GSK3640254 200 mg + DTG 50 mg

EXPERIMENTAL

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.

Drug: GSK3640254; Drug: Dolutegravir

DTG 50 mg + Lamivudine (3TC) 300 mg

ACTIVE COMPARATOR

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.

Drug: Dolutegravir; Drug: Lamivudine capsules; Drug: Lamivudine tablets

Interventions

GSK3640254 DRUG

GSK3640254 was available as 25 mg or 100 mg tablets administered orally.

GSK3640254 100 mg + Dolutegravir (DTG) 50 mg; GSK3640254 150 mg + DTG 50 mg; GSK3640254 200 mg + DTG 50 mg

Dolutegravir DRUG

DTG was available as 50 mg tablets administered orally.

DTG 50 mg + Lamivudine (3TC) 300 mg; GSK3640254 100 mg + Dolutegravir (DTG) 50 mg; GSK3640254 150 mg + DTG 50 mg; GSK3640254 200 mg + DTG 50 mg

Lamivudine capsules DRUG

3TC was available as 300 mg capsules administered orally as a blinded treatment.

DTG 50 mg + Lamivudine (3TC) 300 mg

Lamivudine tablets DRUG

3TC was available as 300 mg tablets administered orally as an unblinded treatment.

DTG 50 mg + Lamivudine (3TC) 300 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Syneos Health: collaborator

Study Sites (44)

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Palm Springs, California, 92262, United States

Location

GSK Investigational Site

Denver, Colorado, 80246, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Miami, Florida, 33140, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64111, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68198, United States

Location

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1405CKC, Argentina

Location

GSK Investigational Site

Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425AGC, Argentina

Location

GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4P9, Canada

Location

GSK Investigational Site

Paris, 75012, France

Location

GSK Investigational Site

Tourcoing, 59208, France

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50668, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Hamburg, 20146, Germany

Location

GSK Investigational Site

Bergamo, Lombardy, 24127, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20127, Italy

Location

GSK Investigational Site

Porto, 4369-004, Portugal

Location

GSK Investigational Site

Vila Nova de Gaia, 4434-502, Portugal

Location

GSK Investigational Site

San Juan, 00909, Puerto Rico

Location

GSK Investigational Site

Durban, 4091, South Africa

Location

GSK Investigational Site

Johannesburg, 2113, South Africa

Location

GSK Investigational Site

Parow, 7505, South Africa

Location

GSK Investigational Site

Vosloorus Ext 2, 1475, South Africa

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Barcelona, 8003, Spain

Location

GSK Investigational Site

Bilbao, 48013, Spain

Location

GSK Investigational Site

Elche, ?03203, Spain

Location

GSK Investigational Site

La Laguna-Tenerife, 38320, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28031, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Murcia, 30120, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07198, Spain

Location

GSK Investigational Site

Sant Boi de Llobregat, 08830, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Vigo, 36312, Spain

Location

Related Publications (1)

• Joshi SR, Masia M, Mitha E, Castagna A, Cordova E, Ramgopal M, Gaudion A, Karthika S, Oyee J, Bainbridge V, Wynne B, Lataillade M. Efficacy and safety of the HIV-1 maturation inhibitor GSK3640254 plus dolutegravir as a two-drug regimen in adults naive to antiretroviral therapy (DYNAMIC): 24-week results from a randomised phase 2b study. EClinicalMedicine. 2025 Oct 17;89:103566. doi: 10.1016/j.eclinm.2025.103566. eCollection 2025 Nov.

  PMID: 41357331 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

GSK3640254; dolutegravir; Lamivudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, parallel-group study.

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: May 25, 2021
• Study Start: August 18, 2021
• Primary Completion: November 22, 2022
• Study Completion: May 11, 2023
• Last Updated: December 14, 2023
• Results First Posted: December 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CA (2); ES (16); FR (2); PR (1); DE (4); ZA (4); AR (3); IT (2); PT (2); US (8)