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

NCT ID: NCT02798978

Last Updated: 2020-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-10
• Study Completion Date: 2017-10-13

Brief 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.

Conditions

Cancer; Neoplasms

Keywords

pharmacokinetics; TLR4 agonist; cancer; tolerability; GSK1795091; pharmacodynamics; safety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: GSK1795091 or Placebo

In Part 1, subjects in sequential cohorts will receive single ascending doses of intravenous (IV) injection of GSK1795091 or matching placebo, with a starting dose of 7 nanogram (ng), on Day 1 until the highest dose is evaluated.

Group Type: EXPERIMENTAL

GSK1795091

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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

Part 2 Cohort 1: GSK1795091

In Part 2 Cohort 1, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and second dose on Day 8 (one week apart)

Group Type: EXPERIMENTAL

GSK1795091

Intervention Type: DRUG

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.

Part 2 Cohort 2: GSK1795091

In Part 2 Cohort 2, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and a second dose on Day 15 (two weeks apart)

Group Type: EXPERIMENTAL

GSK1795091

Intervention Type: DRUG

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.

Interventions

GSK1795091

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Berlin, , Germany

Countries

Germany

References

Hug BA, Matheny CJ, Burns O, Struemper H, Wang X, Washburn ML. Safety, Pharmacokinetics, and Pharmacodynamics of the TLR4 Agonist GSK1795091 in Healthy Individuals: Results from a Randomized, Double-blind, Placebo-controlled, Ascending Dose Study. Clin Ther. 2020 Aug;42(8):1519-1534.e33. doi: 10.1016/j.clinthera.2020.05.022. Epub 2020 Jul 30.

Reference Type: BACKGROUND

PMID: 32739049 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000759-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204685

Identifier Type: -

Identifier Source: org_study_id