A Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A in Viremic Human Immunodeficiency Virus (HIV)-1 Infected Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: GSK3810109A
Intervention description: GSK3810109A will be available as sterile aqueous solution.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: The is a sequential treatment, two-part study which will include a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.
Masking: None (Open Label)
Masking description: This is an open-label study
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Antiretroviral-naïve; Broadly neutralizing antibody; GSK3810109A; HIV; N6LS

Summary:

      This study is to evaluate antiviral activity, efficacy, safety, tolerability,
      pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3810109A in HIV-1 infected treatment
      naive adults. Participants will receive a single dose of GSK3810109A administered either
      intravenously (IV) or subcutaneously (SC). The study includes a screening phase, a randomized
      monotherapy phase and a standard of care follow-up phase.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must be 18 to 65 years of age inclusive, at the time of signing the
             informed consent.

          -  Participants must have HIV-1 infection within 45 days of the Screening Visit: Plasma
             HIV-1 RNA greater than or equal to (>=) 5000 copies/mL (c/mL).

          -  Confirmed screening CD4+ T-cell count >= 350 cells per cubic millimeter (cells/mm3).

          -  Antiretroviral naïve: No Antiretroviral therapy (ARTs) (in combination or monotherapy)
             received after the diagnosis of HIV-1 infection.

          -  Body weight >= 50 kg to less than or equal to (<=) 115 kg.

          -  Male and/or female. Contraceptive use by men or women should be consistent with local
             regulations regarding the methods of contraception for those participating in clinical
             studies. All participants participating in the study should be counselled on safer
             sexual practices including the use and benefit/risk of effective barrier methods (e.g.
             male condom) and on the risk of HIV transmission to an uninfected partner; a.
             Participants who are female at birth are eligible to participate if at least one of
             the following conditions applies: Not Pregnant or breastfeeding and at least one of
             the following conditions applies: Is not a participant of childbearing potential
             (POCBP). OR Is a POCBP and using an acceptable contraceptive method during the
             intervention period (at a minimum until after the last dose of study intervention).
             The investigator should evaluate the effectiveness of the contraceptive method in
             relationship to the first dose of study intervention. A POCBP must have a negative
             highly sensitive pregnancy test (urine or serum as required by local regulations) on
             Day 1, prior to the first dose of study intervention. If a urine test cannot be
             confirmed as negative (example [e.g.], an ambiguous result), a serum pregnancy test is
             required. In such cases, the participant must be excluded from participation if the
             serum pregnancy result is positive.

          -  Corrected QT interval (QTc) Interval <= 450 milliseconds (msec)

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  Participants with primary HIV infection, evidenced by acute retroviral syndrome (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.

          -  Participants who are pregnant, breastfeeding, plan to become pregnant or breastfeed
             during the study.

          -  The participant has an underlying skin disease or disorder (example i.e. infection,
             inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy,
             urticaria) that would interfere with assessment of injection sites.

          -  Known history of cirrhosis with or without viral hepatitis co-infection.

          -  History of clinically relevant hepatitis within last 6 months.

          -  Evidence of Hepatitis B virus (HBV) infection based on the results of testing at
             screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody
             (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV Deoxyribonucleic
             acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants
             negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive
             for HBV DNA are excluded. Participants negative for anti-HBs but positive for anti-HBc
             (negative HBsAg status) and negative for HBV DNA are not excluded.

          -  Participants with Hepatitis C co-infection.

          -  Untreated syphilis infection (positive rapid plasma reagin [RPR] at screening) without
             documentation of treatment. Participants who are one month post completed treatment
             are eligible if recruitment is open.

        Rescreening is allowed after treatment.

          -  Prior receipt of licensed or investigational monoclonal antibody.

          -  Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3
             disease except cutaneous Kaposi's sarcoma not requiring systemic therapy.

          -  Known or suspected moderate or severe hepatic impairment (Class C as determined by
             Child-Pugh Classification) coagulopathy, hypoalbuminemia, esophageal or gastric
             varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the
             exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Clinically significant cardiovascular disease, as defined by history/evidence of
             congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery
             bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty
             (PTCA) or any clinically significant cardiac disease at the discretion of the
             investigator.

          -  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; other localized malignancies require agreement between the
             investigator and the study medical monitor for inclusion of the participant prior to
             randomization.

          -  Any pre-existing physical or mental condition which, in the opinion of the
             investigator, may interfere with the participant's ability to comply with the dosing
             schedule and/or protocol evaluations, or which may compromise the safety of the
             participant.

          -  Participants with substance abuse disorders or social restraints that the investigator
             considers to be possible deterrents to successful completion of the study.

          -  Participants who in the investigator's judgment, pose a significant suicidality risk.
             Participants' history of suicidal behavior and/or suicidal ideation should be
             considered when evaluating for suicide risk.

          -  History of sensitivity to any of the study medications or their components or drugs of
             their class, or a history of drug or other allergy that, in the opinion of the
             investigator or Medical Monitor, contraindicates their participation.

          -  Any condition which, in the opinion of the investigator, may interfere with the
             absorption, distribution, metabolism or excretion of the study drugs, combination ART
             or render the participant unable to take oral medication.

          -  Participants with a positive Corona Virus Disease 2019 (COVID-19) test at Screening.
             Participants with known COVID-19 positive contacts within the past 14 days, or with
             symptoms suggestive of active COVID-19 (fever, cough, myalgias, shortness of breath,
             loss of taste or smell), should be excluded. Participants who remain symptom-free for
             at least 14 days after a COVID-19 exposure are allowed.

          -  Has received any HIV-1 immunotherapeutic vaccine or prophylactic vaccine.

          -  Treatment with any of the following agents within 28 days of screening: radiation
             therapy; cytotoxic chemotherapeutic agents; any systemic immune suppressant;

          -  Exposure to an experimental drug or experimental vaccine within either 28 days, 5
             half-lives of the test agent, or twice the duration of the biological effect of the
             test agent, whichever is longer, prior to the first dose of IP.

          -  Participants receiving any prohibited medication and who are unwilling or unable to
             switch to an alternate medication.

          -  Participant enrolled in a prior or concurrent clinical study that includes a drug
             intervention within the last 30 days.

          -  Any acute laboratory abnormality at Screening, which, in the opinion of the
             investigator, would preclude the participant's inclusion in the study of an
             investigational compound.

          -  Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during
             the Screening period to verify a result.

          -  ALT >= 3 times the upper limit of normal (ULN).

          -  Creatinine clearance of <50 mL/minute/1.73 meter^2) via Chronic Kidney Disease
             Epidemiology Collaboration (CKD-EPI) method.

          -  The participant has a tattoo or other dermatological condition overlying potential
             injection sites which may interfere with interpretation of injection site reactions or
             administration of GSK3810109A.