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
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
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.
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)