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

NCT ID: NCT04493216

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-18
• Study Completion Date: 2023-05-29

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

GSK3640254

Intervention Type: DRUG

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

ABC/3TC

Intervention Type: DRUG

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

FTC/TAF

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

GSK3640254

Intervention Type: DRUG

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

ABC/3TC

Intervention Type: DRUG

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

FTC/TAF

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

GSK3640254

Intervention Type: DRUG

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

ABC/3TC

Intervention Type: DRUG

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

FTC/TAF

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

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

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.

Group Type: ACTIVE_COMPARATOR

ABC/3TC

Intervention Type: DRUG

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

FTC/TAF

Intervention Type: DRUG

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

Dolutegravir

Intervention Type: DRUG

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

Interventions

GSK3640254

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

Intervention Type: DRUG

ABC/3TC

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

Intervention Type: DRUG

FTC/TAF

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

Intervention Type: DRUG

Dolutegravir

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants must be 18 years of age inclusive, at the time of signing the informed consent.
• Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy) received after the diagnosis of HIV-1 infection (for example [e.g.], use of Pre-exposure prophylaxis [PreP] meets inclusion.
• 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.
• For participants enrolled in France: a participant was eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria

• 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).
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
• Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
• Participants who are unwilling to stop any medications as required by the local lab test for Helicobacter (H.) pylori.
• Participants who require concomitant medications known to be associated with a prolonged Corrected QT interval (QTc).
• 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.
• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention (including an investigational Coronavirus Disease (COVID) vaccine) or any other type of medical research.
• Any evidence of viral resistance based on the NRTI backbone selected.
• Historical evidence (prior to study screening period) of the presence of resistance- associated mutations gag A364V or A364A/V.
• Creatinine Clearance <50 mL/minute.
• Alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN) or ALT >=2 times ULN and total bilirubin >=1.5 times ULN.
• Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and reflex HBV deoxyribonucleic acid (DNA) as follows:

1. Participants positive for HBsAg were excluded;

2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA on reflex testing were excluded.

• Positive Hepatitis C antibody test result at Screening and positive on reflex to Hepatitis C RNA.
• Positive test results for H. pylori;
• Known or suspected active COVID-19 infection or contact with an individual with known COVID-19, within 14 days of study enrollment
• Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening) without documentation of treatment.
• Presence of moderate-to-severe hepatic impairment (Class B or C) as determined by Child-Pugh classification.
• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator or ViiV Medical Monitor, would preclude participation in the study of an investigational compound.
• Urine Drug Screen positive (showing presence of): Amphetamines, Barbiturates, Cocaine, 3,4-Methyl enedioxy methamphetamine (MDMA) or Phencyclidine, or non-prescribed opiates, oxycodone, benzodiazepines, methadone, methamphetamines or tricyclic antidepressants.
• Any clinically relevant Grade 4 laboratory abnormality at Screen, including results for creatine phosphokinase (CPK) and lipid abnormalities that lack a compelling explanation from the Investigator.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 28 days.
• Exposure to more than 4 new investigational drugs or vaccines (exclusive of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential indication within 12 months prior to the first dosing day;
• Treatment with radiation therapy or cytotoxic chemotherapeutic agents or any systemic immunosuppressive agent within 30 days of study drug administration or anticipated need for such treatment within the study;
• ECG Heart Rate <50 beats per minute (bpm) or >100 bpm, or QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds (msec).
• For Portugal only: HIV-2 infection (either determined by prior testing, medical history, or obtained locally during the Screening window).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Ft. Pierce, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Berkley, Michigan, United States

GSK Investigational Site

Jackson, Mississippi, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

San Juan, , Argentina

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Marseille, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Tourcoing, , France

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Bochum, North Rhine-Westphalia, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Turin, Piedmont, Italy

GSK Investigational Site

Brescia, , Italy

GSK Investigational Site

Milan, , Italy

GSK Investigational Site

Almada, , Portugal

GSK Investigational Site

Aveiro, , Portugal

GSK Investigational Site

Porto, , Portugal

GSK Investigational Site

Porto, , Portugal

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Samara, , Russia

GSK Investigational Site

Smolensk, , Russia

GSK Investigational Site

Johannesburg, Gauteng, South Africa

GSK Investigational Site

Wentworth, KwaZulu-Natal, South Africa

GSK Investigational Site

Observatory, Cape Town, , South Africa

GSK Investigational Site

Vosloorus Ext 2, , South Africa

GSK Investigational Site

A Coruña, , Spain

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Badalona, Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

L'Hospitalet de Llobregat, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Marbella, , Spain

GSK Investigational Site

Málaga, , Spain

GSK Investigational Site

Murcia, , Spain

GSK Investigational Site

Palma de Mallorca, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Zurich, , Switzerland

Countries

United States; Argentina; Canada; France; Germany; Italy; Portugal; Russia; South Africa; Spain; Switzerland

References

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.

Reference Type: DERIVED

PMID: 34996113 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

208379

Identifier Type: -

Identifier Source: org_study_id