A Dose-Range Finding Clinical Trial Study in Human Immunodeficiency Virus (HIV-1) Infected Treatment-Naive Adults

NCT04493216 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 208379
• Study Type: interventional
• Target: 161
• Locations: 11 countries
• Sites: 65

Brief Summary

This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses \[100, 150 and 200 milligrams {mg}\]), active controlled clinical trial. It aims to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine \[ABC/3TC\] or emtricitabine/tenofovir alafenamide \[FTC/TAF\]).

Conditions

HIV Infections

Keywords

HIV infection; GSK3640254; Nucleoside Reverse Transcriptase Inhibitor; Dolutegravir; Abacavir (ABC)/Lamivudine (3TC); Emtricitabine (FTC)/tenofovir alafenamide (TAF); Maturation Inhibitor

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 was assessed using the Food and Drug Administration (FDA) snapshot algorithm to demonstrate the antiviral activity of GSK3640254 given in combination with either ABC/3TC or FTC/TAF compared to the reference treatment of DTG given in combination with either ABC/3TC or FTC/TAF.

  At Week 24

Secondary Outcomes (18)

• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48

  At Week 48

• Absolute Values of HIV-1 RNA at Weeks 24 and 48

  Baseline (Day 1) and at Weeks 24 and 48

• Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48

  Baseline (Day 1) and at Weeks 24 and 48

• Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48

  Baseline (Day 1) and at Weeks 24 and 48

• Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48

  Baseline (Day 1) and at Weeks 24 and 48

Study Arms (4)

GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF

EXPERIMENTAL

Participants with human immunodeficiency virus type 1 (HIV-1), orally received one 100 mg tablet per day of GSK3640254 and two tablets per day of matching placebo in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day of 600 mg abacavir (ABC) / 300 mg lamivudine (3TC) OR 200 mg emtricitabine (FTC) / 25 mg tenofovir alafenamide (TAF) orally.

Drug: GSK3640254; Drug: ABC/3TC; Drug: FTC/TAF; Drug: Placebo

GSK3640254 150 mg + ABC/3TC or FTC/TAF

EXPERIMENTAL

Participants with HIV-1, orally received 150 mg (one 100 mg tablet + two 25 mg tablets per day) of GSK3640254 in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally.

Drug: GSK3640254; Drug: ABC/3TC; Drug: FTC/TAF

GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF

EXPERIMENTAL

Participants with HIV-1, orally received two 100 mg tablets (200 mg) per day of GSK3640254 and one tablet per day of matching placebo in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally.

Drug: GSK3640254; Drug: ABC/3TC; Drug: FTC/TAF; Drug: Placebo

Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF

ACTIVE COMPARATOR

Participants with HIV-1, orally received one 50 mg tablet per day of DTG in an open label setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally.

Drug: ABC/3TC; Drug: FTC/TAF; Drug: Dolutegravir

Interventions

GSK3640254 DRUG

GSK3640254 was available as a 25 mg and 100 mg tablets to be administered via oral route.

GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF; GSK3640254 150 mg + ABC/3TC or FTC/TAF; GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF

ABC/3TC DRUG

ABC/3TC was available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.

Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF; GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF; GSK3640254 150 mg + ABC/3TC or FTC/TAF; GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF

FTC/TAF DRUG

FTC/TAF was available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.

Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF; GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF; GSK3640254 150 mg + ABC/3TC or FTC/TAF; GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF

Dolutegravir DRUG

Dolutegravir was available as a 50 mg tablet to be administered via oral route.

Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF

Placebo DRUG

Placebo matching GSK3640254 was administered in the form of tablets via oral route.

GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF; GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 years of age inclusive, at the time of signing the informed consent.
• Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (\>=)1000 c/mL.
• Screening CD4+ T-cell count \>=250 cells/mm\^3.
• Antiviral susceptibility to the NRTI backbone selected should be demonstrated
• Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index (BMI) greater than (\>)18.5 kg/meter square (m\^2).Calculations utilized sex assigned at birth
• Participants who are male at birth and participants who are female at birth.
• Participants who are female at birth: Contraceptive use by participant who are female at birth should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A participant who was female at birth was eligible to participate if they were not pregnant or breastfeeding, and one of the following conditions applies:
• Was a participant of non-childbearing potential (PONCBP)
• Or was a POCBP and using an acceptable contraceptive method during the study intervention period (at a minimum until after the last dose of study intervention).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy.
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.
• Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
• Known history of liver cirrhosis with or without viral hepatitis co-infection.
• 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.
• History of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
• Any history of significant underlying psychiatric disorder, in the opinion of the Investigator or ViiV Medical Monitor, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder or a clinical assessment of suicidality based on the responses on the Columbia-Suicide Severity Rating Scale (eCSSRS).
• 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.
• Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the Investigator or ViiV Medical Monitor (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.
• A pre-existing condition, in the opinion of the Investigator or ViiV 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 drugs or render the participant unable to take oral study treatment.
• Myocardial infarction in the past 3 months.
• Familial or personal history of long QT syndrome or sudden cardiac death.
• Medical history, current or historical, of significant cardiac arrhythmias or Electrocardiogram (ECG) findings which, in the opinion of the Investigator or ViiV Medical Monitor, will interfere with the safety of the participant.
• 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).

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (65)

GSK Investigational Site

Los Angeles, California, 90027, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Berkley, Michigan, 48072, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39216-4505, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68198, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45267-0405, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1128AAF, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1207AAP, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425AWK, Argentina

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Buenos Aires, 1141, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425AGC, Argentina

Location

GSK Investigational Site

San Juan, 5400, Argentina

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4P9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Marseille, 13003, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Tourcoing, 59208, France

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44787, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50674, Germany

Location

GSK Investigational Site

Rome, Lazio, 00149, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20127, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10149, Italy

Location

GSK Investigational Site

Brescia, 25123, Italy

Location

GSK Investigational Site

Milan, 20157, Italy

Location

GSK Investigational Site

Almada, 2801-951, Portugal

Location

GSK Investigational Site

Aveiro, 3814-501, Portugal

Location

GSK Investigational Site

Porto, 4099-001, Portugal

Location

GSK Investigational Site

Porto, 4200-319, Portugal

Location

GSK Investigational Site

Kazan', 420061, Russia

Location

GSK Investigational Site

Saint Petersburg, 190103, Russia

Location

GSK Investigational Site

Saint Petersburg, 191167, Russia

Location

GSK Investigational Site

Samara, 443029, Russia

Location

GSK Investigational Site

Smolensk, 214006, Russia

Location

GSK Investigational Site

Johannesburg, Gauteng, 2113, South Africa

Location

GSK Investigational Site

Wentworth, KwaZulu-Natal, 4052, South Africa

Location

GSK Investigational Site

Observatory, Cape Town, 7925, South Africa

Location

GSK Investigational Site

Vosloorus Ext 2, 1475, South Africa

Location

GSK Investigational Site

A Coruña, 15006, Spain

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Badalona, Barcelona, 8916, Spain

Location

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Marbella, 29600, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Murcia, 30003, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07010, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Seville, 41014, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

Location

GSK Investigational Site

Valencia, 46014, Spain

Location

GSK Investigational Site

Zurich, 8091, Switzerland

Location

Related Publications (2)

• Joshi SR, Cordova E, Mitha E, Castagna A, Ramgopal M, Llibre JM, Potthoff A, Chernova OE, Nunez SA, Man C, Jeffrey JL, Fishman C, Oyee J, Joshi A, Zhang Y, Bainbridge V, Wynne B, Lataillade M. Efficacy and safety of the HIV-1 maturation inhibitor GSK3640254 plus two NRTIs in adults naive to antiretroviral therapy (DOMINO): 24-week results from a randomised phase 2b study. EClinicalMedicine. 2025 Oct 17;89:103567. doi: 10.1016/j.eclinm.2025.103567. eCollection 2025 Nov.

  PMID: 41357330 DERIVED

• Spinner CD, Felizarta F, Rizzardini G, Philibert P, Mitha E, Domingo P, Stephan CJ, DeGrosky M, Bainbridge V, Zhan J, Dumitrescu TP, Jeffrey JL, Xu J, Halliday F, Gan J, Johnson M, Gartland M, Joshi SR, Lataillade M. Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254. Clin Infect Dis. 2022 Sep 14;75(5):786-794. doi: 10.1093/cid/ciab1065.

  PMID: 34996113 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

GSK3640254; dolutegravir

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

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study treatment assignments was not blinded (GSK3640254 versus Dolutegravir control arm). However, 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. The Sponsor personnel remained blinded until the database lock for the Week 24 analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 30, 2020
• Study Start: November 18, 2020
• Primary Completion: September 5, 2022
• Study Completion: May 29, 2023
• Last Updated: June 26, 2024
• Results First Posted: November 18, 2023

Record last verified: 2024-05

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, 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

AR (8); DE (3); PT (4); CH (1); FR (3); ZA (4); IT (6); CA (4); RU (5); ES (18); US (9)