A Phase I, 2-part (Part 1 Being a Single Dose Escalation and Part 2, a Parallel Group) Study of Toll-like Receptor (TLR4) Agonist (GSK1795091) in Healthy Subjects
Condition: Cancer; Neoplasms
Intervention: GSK1795091; Placebo
Intervention description: GSK1795091 will be supplied as solution for injection vial. Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.; Matching placebo will be supplied as a solution for injection vial and will be administered as IV bolus over 2-5 min followed by a IV bolus of 10 mL normal saline
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: pharmacokinetics; TLR4 agonist; cancer; tolerability; GSK1795091; pharmacodynamics; safety

Summary:

      This study is an ascending dose first-time-in-human study to determine the safety,
      tolerability, pharmacodynamic (PD), and pharmacokinetics (PK) profile of GSK1795091 in
      healthy subjects. The results will support the design of future clinical trials of GSK1795091
      administered to subjects with advanced malignancies in combination with immune system
      modulators.

      Part 1 will be a randomized, double-blind (sponsor-unblinded), placebo-controlled, single
      center, single dose escalation, sequential group evaluation of intravenously administered
      GSK1795091 to evaluate the safety and tolerability in healthy subjects. Part 2 will be an
      open-label, parallel group evaluation of 2 doses of GSK1795091 administered, either 1 week
      apart (Part 2, Cohort 1) or 2 weeks apart (Part 2, Cohort 2). In Part 2, on Day 1, subjects
      will receive intravenous GSK1795091 at a dose determined by results from Part 1. The total
      duration of this study is approximately 10 weeks from screening to the last study visit.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between 18 and 50 years of age inclusive, at the time of signing the informed consent.

          -  Healthy as determined by the investigator or medically qualified designee based on a
             medical evaluation including medical history, physical examination, laboratory tests,
             vital signs and 12-lead ECG. (A subject with a clinically insignificant abnormality or
             laboratory parameter(s) may be included only if the Investigator documents that the
             finding is unlikely to represent a safety risk and will not interfere with the study
             procedures.)

          -  Body weight 55-95 kilogram (kg) and body mass index within the range 19-30 kg/meter
             (m)^2 (inclusive).

          -  Male or Female of non-childbearing potential:

        Males: Male subjects with female partners of child bearing potential must comply with the
        pre specified contraception requirements.

        Females: A female subject is eligible to participate if she is not pregnant (as confirmed
        by a negative serum or urine human chorionic gonadotropin test), not lactating, and is
        either of non-reproductive potential or reproductive potential. If of reproductive
        potential, then the subject should agree to follow one of the options listed per GSK
        Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
        Potential from 30 days prior to the first dose and until 30 days after the last dose of
        study medication The Investigator is responsible for ensuring that subjects understand how
        to properly use these methods of contraception

          -  Capable of giving signed informed consent

        Exclusion Criteria:

          -  History of any significant medical condition (e.g. cardiac, pulmonary, metabolic,
             renal, gastrointestinal, rheumatological, etc.)

          -  History of frequent (>1 per week) headache or myalgia, asthma, syncope.

          -  History of liver disease, or known hepatic or biliary abnormalities (with the
             exception of Gilbert's syndrome).

          -  Alanine aminotransferase (ALT) and bilirubin >1.1×upper limit of normal (ULN; isolated
             bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin
             <35%).

          -  Vital signs:

        Systolic blood pressure (SBP) <90 and >140 milliliter of mercury (mmHg); diastolic BP <50
        and >90 mmHg; heart rate (HR) <50 and >90 beats per minute (bpm); temperature >37.5 degree
        Celsius

          -  Clinically significant ECG abnormality and/or HR < 50 and >90 bpm; PR interval >220
             milliseconds (msec); QRS duration >120 msec; and QTcF > 450 msec

          -  Anticipated requirement for any prescription medication during the study

          -  History of regular alcohol consumption within 6 months of the study averaging a weekly
             intake of >14 drinks for males or >7 drinks for females or inability to abstain from
             alcohol from 1 day prior to the inpatient period of the study until discharge (one
             drink is equivalent to 8 grams of alcohol: 200 milliliter [mL] of beer, 100 mL of wine
             or 1 measure (25 mL) of spirits)

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco or
             nicotine-containing products within 2 months prior to screening or inability to
             abstain from smoking during the study

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or Medical
             Monitor, contraindicates their participation

          -  Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at
             screening or within 3 months prior to first dose of study treatment. Subjects with
             positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a
             confirmatory negative Hepatitis C ribonucleic acid polymerase chain reaction test is
             obtained.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for human immunodeficiency antivirus antibody.

          -  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 visit (Day -2) in the
             current study: 30 days, 5 half-lives or twice the duration of the biological effect of
             the investigational product (whichever is longer).

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             visit (Day -2).

          -  Exposure to GSK1795091 in a previous cohort of this study.

          -  Subject is unable to refrain from taking non-prescription drugs (including vitamins
             and dietary or herbal supplements), within 7 days prior to the first dose of study
             medication until completion of the follow-up visit, unless in the opinion of the
             investigator and sponsor, the medication will not interfere with the study.

          -  Subject is able to understand and communicate in German/or native language of the
             site. Subject, or close relative of the subject, is the investigator or a
             sub-investigator, research assistant, pharmacist, study coordinator, or other staff
             directly involved with the conduct of the study at that site

          -  Vulnerable subjects (eg subjects kept in detention)