First Time in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of GSK3389404 in Healthy Subjects
Condition: Hepatitis B
MeSH terms: Hepatitis B
Intervention: GSK3389404; Matching Placebo
Intervention description: GSK3389404 is supplied as solution for injection vial. Each vial contains 100 mg/mL of GSK3389404. It's physical appearance is clear colourless to slightly yellow solution.; Placebo is supplied as solution for injection vial. It's physical appearance is clear colourless solution.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Single dose; Multiple ascending doses (MAD); Pharmacokinetics; Safety; GSK3389404; Tolerability

Summary:

      This study is a Phase 1, randomized, double-blind (Sponsor unblinded), placebo controlled,
      dose escalation study to determine the safety, tolerability and pharmacokinetics (PK) profile
      of GSK3389404 as single (Part 1) and multiple subcutaneous (SC) injections (Part 2) in
      healthy subjects. This study represents the first administration of GSK3389404 in humans to
      define the safety, tolerability and PK following single and multiple doses of GSK3389404 in
      healthy subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  The subject is able to understand and comply with protocol requirements, instructions
             and protocol-stated restrictions and is likely to complete the study as planned.

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, laboratory tests and
             electrocardiograms (ECGs). There should be no evidence of cardiac, pulmonary, hepatic,
             biliary, gastrointestinal, or renal disorders, or cancer within the past 5 years
             (except localized or in situ cancer of the skin). A subject with a clinical
             abnormality or laboratory parameter(s) which is/are not specifically listed in the
             inclusion or exclusion criteria and are reported as outside of the normal reference
             range for healthy subjects may be included only if the Investigator considers the
             finding unlikely to introduce additional risk to the subject and will not interfere
             with the study procedures.

          -  Male or female between 18 and 55 years of age, inclusive, at the time of signing the
             informed consent form (ICF).

          -  Body weight >50 kilograms (kg) (110 pounds [lb]) for men and >45 kg (99 lb) women and
             a body mass index (BMI) between 18 to 30 kg/meter-squared, inclusive, will be allowed.

          -  AST, ALT, ALP, bilirubin, and creatinine within the normal reference range. If outside
             the normal reference range, these values may be repeated once at the discretion of the
             Investigator or designee.

          -  WBC count (including neutrophil counts), haemoglobin and platelets within the normal
             reference range. If outside the normal reference range, these values may be repeated
             once at the discretion of the Investigator or designee.

          -  Females of Reproductive Potential (FRP) are not permitted. Eligible females must meet
             the following criteria:

               -  Non-pregnant (as confirmed by a negative serum human chorionic gonadotrophin
                  (hCG) test); AND

               -  Non-lactating at screening and prior to dosing; AND

               -  Non-reproductive potential as defined by at least one of the following
                  conditions: Pre-menopausal females without reproductive potential defined by one
                  of the following: Documented salpingectomy, Hysterectomy, Documented bilateral
                  oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea; A
                  blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol
                  levels may be conducted at the discretion of the Investigator or site to confirm
                  non-reproductive potential.

          -  Male subjects with female partners of child-bearing potential must agree to meet one
             of the contraception requirements from the time of first dose of study treatment until
             the last follow-up visit (Part 1 Day 60; Part 2 Day 113).

               -  Vasectomy with documentation of azoospermia.

               -  Male condom plus partner use of one of the contraceptive options below that meets
                  the standard operating procedure (SOP) effectiveness criteria including a <1%
                  rate of failure per year, as stated in the product label: Contraceptive subdermal
                  implant; Intrauterine device or intrauterine system; Combined estrogen and
                  progestogen oral contraceptive; Injectable progestogen; Contraceptive vaginal
                  ring; Percutaneous contraceptive patches These allowed methods of contraception
                  are only effective when used consistently, correctly and in accordance with the
                  product label. The Investigator is responsible for ensuring that subjects
                  understand how to properly use these methods of contraception.

        Exclusion Criteria:

          -  History or other clinical evidence of hypertension, significant or unstable cardiac
             disease (e.g., prolonged QT syndrome [torsade de pointes], angina, congestive heart
             failure, myocardial infarction, diastolic dysfunction, significant arrhythmia,
             coronary heart disease and/or clinically significant ECG abnormalities).

          -  History of, or active diagnosis of, liver disease such as Gilbert's syndrome,
             cirrhosis, autoimmune hepatitis, non-alcoholic fatty liver disease /non-alcoholic
             steatohepatitis, or hemochromatosis.

          -  History of, or active diagnosis of, primary or secondary (e.g., renal disease
             secondary to diabetes, hypertension, vascular disease, etc.) renal disease.

          -  History of bleeding diathesis or coagulopathy.

          -  History of regular alcohol consumption within 6 months of the study defined as: An
             average weekly intake of >21 units for males or >14 units for females. One unit is
             equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliters [mL])
             of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

          -  Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until the
             last dose in each dosing session.

          -  Regular use of tobacco- or nicotine-containing products within 3 months prior to
             screening.

          -  History of sensitivity to GSK3389404 or components thereof or a history of drug or
             other allergy that, in the opinion of the investigator or GSK Medical Monitor,
             contraindicates their participation.

          -  Use of prescription or non-prescription drugs, including vitamin, dietary and herbal
             supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
             potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
             dose of study treatment.

          -  Use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days prior
             to the first dose of study treatment.

          -  A positive hepatitis C antibody.

          -  A positive pre-study Hepatitis B surface antigen (HBsAg).

          -  A positive test for human immunodeficiency virus (HIV) antibody.

          -  Serum creatinine greater than the upper limit of normal (ULN)

          -  Glomerular filtration rate <90 mL/minute as calculated by the Chronic Kidney Disease
             Epidemiology Collaboration (CKD-epi) formula

          -  Albumin to creatinine ratio (ACR) >= 0.03 milligram/milligram (mg/mg). In the event of
             an ACR above this threshold, eligibility may be confirmed by a second measurement.

          -  Qualitative test (urinalysis) for blood in urine >= 0.03 mg/deciliter. In the event of
             a positive test, the test may be repeated once, and if negative, the subject
             considered eligible.

          -  A positive pre-study drug screen. Unwilling to refrain from use of the illicit drugs
             and adhere to other protocol-stated restrictions while participating in the study.

          -  Fridericia's QT correction formula (QTcF) >= 450 milliseconds (msec).

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 5 half-lives (if known) or twice the duration (if known) of the biological
             effect of the study drug (whichever is longer) or 90 days (if half-life or duration is
             unknown).

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day.

          -  Prior treatment with any oligonucleotide or small interfering ribonucleic acid (siRNA)
             within 12 months prior to the first dosing day.