A Dose-Range Finding Clinical Trial Study in Human Immunodeficiency Virus (HIV-1) Infected Treatment-Naive Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: GSK3640254; ABC/3TC; FTC/TAF; Dolutegravir; Placebo
Intervention description: GSK3640254 will be available as a 25 mg and 100 mg tablets to be administered via oral route.; ABC/3TC will be available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.; FTC/TAF will be available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.; Dolutegravir will be available as a 50 mg tablet to be administered via oral route.; Placebo matching GSK3640254 will be administered in the form of tablets via oral route.
Intervention MeSH terms: Dolutegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a randomized, multicenter, parallel group study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: The study treatment assignments will not be blinded (GSK3640254 versus Dolutegravir control arm). However, the dose level of GSK3640254 in each of the treatment arms containing GSK3640254 will be blinded to the research participants and all study personnel during the study. The Sponsor personnel will also remain blinded until the database lock for the Week 24 analysis.
Enrollment: 169.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV infection; GSK3640254; Nucleoside Reverse Transcriptase Inhibitor; Dolutegravir; Abacavir (ABC)/Lamivudine (3TC); Emtricitabine (FTC)/tenofovir alafenamide (TAF); Maturation Inhibitor

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 will aim 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])
    

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 will utilize 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 is female at birth is eligible to participate if they are not
             pregnant or breastfeeding, and one of the following conditions applies:

               -  Is a participant of non-childbearing potential (PONCBP)

               -  Or is 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 will be 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 are excluded;

               2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg
                  status) and positive for HBV DNA on reflex testing are 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).