CancerPhase 1NCT02798978
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 1 study testing GSK1795091 in people with Cancer and Neoplasms, run by GlaxoSmithKline at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- What is being tested?
- GSK1795091
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteGermany
- Study dates
- 10 Jan 2017to 13 Oct 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A 2-part Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled, Ascending Dose and Parallel Group Study of TLR4 Agonist (GSK1795091) Administered to 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.
- Being tested
- GSK1795091, Placebo
- Keywords
- pharmacokinetics, TLR4 agonist, cancer, tolerability, GSK1795091, pharmacodynamics, safety
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1795091Drug
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.
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Part 1: GSK1795091 or Placebo | Experimental | 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. Receives: Drug: GSK1795091; Drug: Placebo |
| Part 2 Cohort 1: GSK1795091 | Experimental | 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) Receives: Drug: GSK1795091 |
| Part 2 Cohort 2: GSK1795091 | Experimental | 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) Receives: Drug: GSK1795091 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants enrolled into the study who have received a dose of study medication (GSK1795091 or placebo) were included in the All Subjects Population. Participants with non-serious AEs (5 percentage threshold) and SAEs has been reported.
Measured: Up to Day 32
Change From Baseline in Body Temperature Part 1
Body temperature was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Measured: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Part 1
Systolic and diastolic BP was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Measured: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Change From Baseline in Pulse Rate Part 1
Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Measured: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Change From Baseline in Respiratory Rate Part 1
Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Measured: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Number of Participants With Hematology Parameters Outside Reference Range Part 1
Hematology parameters included hemoglobin (HGB), hematocrit (HCT), Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Reference range for basophil was 0.01 - 0.07*10^9/Liters (L), eosinophils 0.03 - 0.5*10^9/L, HCT 0.38 - 0.48 proportion of RBC in blood, HGB 126 - 165*gram (g)/L, lymphocytes 1.08 - 3*10^9/L, MCH 26.3 - 32.8*picogram (pg), MCHC 324 - 359*g/L, MCV 77 - 94.9*femtoliter (fL), monocytes 0.3 - 0.92*10^9/L, neutrophils 1.46 - 5.85*10^9/L, platelets 155 - 342*10^9/L, erythrocytes 4.12 - 5.74*10^12/L, leukocytes 3.19 - 8.71*10^9/L. Values below these ranges were considered as low and above these ranges were considered as high (H). Data for participants from any visit post-screening with values > reference range high and < reference range low are report.
Measured: Up to Day 7
Number of Participants With Clinical Chemistry Parameters Outside Reference Range
Clinical chemistry parameters with reference range were albumin 35-52*g/L, Alkaline phosphatase (ALP) 30-120*International units/L (IU/L), Alanine aminotransferase (ALT) 0-50 * IU/L, Aspartate aminotransferase (AST) 0-50*IU/L, direct bilirubin 0-3.4* micromoles/L (µmol/L), bilirubin 5-21*µmol/L, calcium 2.2-2.65* millimoles/L (mmol/L), cholesterol 0-5.19* mmol/L, creatinine 59-104* µmol/L, C-reactive protein (CRP) 0-5*milligram (mg)/L,Gamma Glutamyl Transferase (GGT) 4.1-5.9*mmol/L, high density lipoproteins (HDL) cholesterol 0.99-2.32*mmol/L, potassium 3.5-5.1*mmol/L, low density lipoproteins (LDL) cholesterol 0-3.3*mmol/L, protein 66-83*g/L, sodium 136-146 * mmol/L, triglycerides 0-2.25 * mmol/L, glucose 4.1-5.9*mmol/L, and urea 2.8-7.2*mmol/L. Values below these ranges were considered as low and above these ranges were considered as high. Data for participants from any visit post-screening with values > reference range high and < reference range low are reported.
Measured: Up to Day 7
Casts, Round Epithelial Cells (REC), Squamous Epithelial Cells (SEC), Urine Erythrocytes and Urine Leukocytes at Indicated Time Points
Urinalysis included microscopic examination parameters like Casts, REC, SEC, Urine erythrocytes and Urine leukocytes. Data at indicated time points were reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). NA indicates standard deviation could not be calculated as only 1 participant was analyzed at the given time point.
Measured: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Ketones and Urine Glucose at Indicated Time Points
Urinalysis included parameters like ketones and urine glucose. Data at indicated time points were reported.
Measured: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Occult Blood at Indicated Time Points
Urinalysis included parameter like Occult blood. Data at indicated time points were reported.
Measured: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urine Protein at Indicated Time Points
Urinalysis included parameter like Urine protein. Data at indicated time points were reported.
Measured: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Specific Gravity at Indicated Time Points
Urinalysis included parameter like specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
Measured: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urine Potential of Hydrogen (pH) at Indicated Time Points
Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Measured: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Number of Participants With Abnormal Electrocardiograms (ECG) Findings Worst Case Post-Baseline
Single measurements of 12-lead ECGs were obtained after 10 minutes of rest in a semi-supine position for the participant. Participants with abnormal ECG findings that are clinically not significant (NCS) and clinically significant (CS) data has been presented here. The data of worst case post-Baseline is presented here.
Measured: Up to Day 32
Secondary outcomes (40)
Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 1
Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated for each participant using a non-compartmental method. All participants for whom, at least, one valid and evaluable pharmacokinetic parameter (AUC or Cmax) was derived were included in PK Parameter Population. Only those participants with data available at the specified data points were analyzed.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 1
Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Partial Area Under the Concentration-time Curve to Time t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 1
Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. AUC (0-t) was used interchangeably with AUC to last time of quantifiable concentration (AUC[0-last]) .Only those participants with data available at the specified data points were analyzed.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Clearance (CL) of GSK1795091 for Part 1
Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Volume of Distribution of GSK1795091 for Part 1
Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of IL-6. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. All participants in the "All Subjects Population" for whom valid and evaluable pharmacodynamic parameters were derived are included in Pharmacodynamic (PD) Population. Data from multiplex immunoassay has been reported.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Tumor Necrosis Factor (TNF)-Alpha From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of TNF-alpha. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. Data from multiplex immunoassay has been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Interferon (IFN)-Gamma From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of IFN-gamma. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. Data from multiplex immunoassay has been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Inducible Protein (IP)-10 From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of IP-10. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Monocyte Chemotactic Protein 1 (MCP-1) From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of MCP-1. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Colony Stimulating Factor 2 (GCSF) From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of GCSF. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Interleukin 1 Receptor Antagonist (IL-1Ra) From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of IL-1Ra. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Interleukin 10 (IL-10) From Baseline for Part 1
Blood samples were collected at indicated time points for the assessment of IL-10. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Change From Baseline in WBC Differential for Part 1
WBC differential included Lymphocytes Count, Monocytes Count, Granulocytes Count including neutrophils and eosinophil. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Measured: Baseline, 4, 24 and 144 hours
Change From Baseline in CRP for Part 1
Blood samples were collected at indicated time points for the assessment of CRP. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Measured: Baseline, Days 2, 4 and 7
Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 2
Cmax assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of Adverse events (AEs) of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 2
Tmax and t1/2 assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Partial Area Under the Concentration-time Curve to Time = t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 2
AUC (0-t) and AUC (0-inf) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Area Under the Concentration-time Curve (AUC) Time Curve for a Dosing Interval (AUC[0-tau]), AUC (0-last) of GSK1795091 for Part 2
AUC (0-tau) and AUC (0-last) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Clearance (CL) of GSK1795091 for Part 2
CL assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Volume of Distribution of GSK1795091 for Part 2
Volume of distribution assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Accumulation Ratio of GSK1795091 for Part 2
Accumulation ratio assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Time Invariance of GSK1795091 for Part 2
Time invariance assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 2
IL-6 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of TNF-alpha From Baseline for Part 2
TNF-alpha assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IFN-gamma From Baseline for Part 2
IFN-gamma assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IP-10 From Baseline for Part 2
IP-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of MCP-1 From Baseline for Part 2
MCP-1 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of GCSF From Baseline for Part 2
GCSF assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IL-1Ra From Baseline for Part 2
IL-1Ra assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IL-10 From Baseline for Part 2
IL-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Change From Baseline in WBC Differential for Part 2
WBC differential assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline, 2, 24 and 144 hours
Number of Participants With Urinalysis Parameters Outside Reference Range for Part 2
Urinalysis as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Up to Day 7
Number of Participants With Hematology Parameters Outside Reference Range in Part 2
Hematology as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Up to Day 7
Number of Participants With Clinical Chemistry Parameters Outside Reference Range in Part 2
Clinical chemistry as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Up to Day 7
Change From Baseline in CRP for Part 2
CRP assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline and Pre-dose, 1, 2, 4, 8, 12, 16, 24, and 48 hours post dose
Change From Baseline in Body Temperature for Part 2
Body temperature was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline and up to Day 7
Change From Baseline in SBP and DBP for Part 2
SBP and DBP was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline and up to Day 7
Change From Baseline in Respiratory Rate for Part 2
Respiratory rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline and up to Day 7
Change From Baseline in Pulse Rate for Part 2
Pulse rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Measured: Baseline and up to Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study start10 Jan 2017
- Primary completion13 Oct 2017
- Study completion13 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02798978
- Sponsor's protocol ID
- 204685
- Other IDs
- 2016-000759-28, 2016
- Status last verified
- Nov 2020
- First submitted
- 9 Jun 2016
- Last updated
- 27 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study is available via the Clinical Study Data Request site.
Publications
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.
PubMed 32739049
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 2-part Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled, Ascending Dose and Parallel Group Study of TLR4 Agonist (GSK1795091) Administered to Healthy Subjects
- ClinicalTrials.gov ID
- NCT02798978
- Acronym / sponsor ID
- 204685
- Keywords
- pharmacokinetics, TLR4 agonist, cancer, tolerability, GSK1795091, pharmacodynamics, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Jan 2017 (actual)
- Primary completion
- 13 Oct 2017 (actual)
- Study completion
- 13 Oct 2017 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Posted 10 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: GSK1795091 or Placebo | Experimental | Drug: GSK1795091, Drug: PlaceboIn 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. |
| Part 2 Cohort 1: GSK1795091 | Experimental | Drug: GSK1795091In 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) |
| Part 2 Cohort 2: GSK1795091 | Experimental | Drug: GSK1795091In 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) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK1795091GSK1795091 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. | Drug | Part 1: GSK1795091 or Placebo, Part 2 Cohort 1: GSK1795091, Part 2 Cohort 2: GSK1795091 |
| PlaceboMatching 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 | Drug | Part 1: GSK1795091 or Placebo |
Primary outcome
Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: Up to Day 32
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants enrolled into the study who have received a dose of study medication (GSK1795091 or placebo) were included in the All Subjects Population. Participants with non-serious AEs (5 percentage threshold) and SAEs has been reported.
Change From Baseline in Body Temperature Part 1
Time frame: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Body temperature was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Part 1
Time frame: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Systolic and diastolic BP was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Change From Baseline in Pulse Rate Part 1
Time frame: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Change From Baseline in Respiratory Rate Part 1
Time frame: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Number of Participants With Hematology Parameters Outside Reference Range Part 1
Time frame: Up to Day 7
Hematology parameters included hemoglobin (HGB), hematocrit (HCT), Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Reference range for basophil was 0.01 - 0.07*10^9/Liters (L), eosinophils 0.03 - 0.5*10^9/L, HCT 0.38 - 0.48 proportion of RBC in blood, HGB 126 - 165*gram (g)/L, lymphocytes 1.08 - 3*10^9/L, MCH 26.3 - 32.8*picogram (pg), MCHC 324 - 359*g/L, MCV 77 - 94.9*femtoliter (fL), monocytes 0.3 - 0.92*10^9/L, neutrophils 1.46 - 5.85*10^9/L, platelets 155 - 342*10^9/L, erythrocytes 4.12 - 5.74*10^12/L, leukocytes 3.19 - 8.71*10^9/L. Values below these ranges were considered as low and above these ranges were considered as high (H). Data for participants from any visit post-screening with values > reference range high and < reference range low are report.
Number of Participants With Clinical Chemistry Parameters Outside Reference Range
Time frame: Up to Day 7
Clinical chemistry parameters with reference range were albumin 35-52*g/L, Alkaline phosphatase (ALP) 30-120*International units/L (IU/L), Alanine aminotransferase (ALT) 0-50 * IU/L, Aspartate aminotransferase (AST) 0-50*IU/L, direct bilirubin 0-3.4* micromoles/L (µmol/L), bilirubin 5-21*µmol/L, calcium 2.2-2.65* millimoles/L (mmol/L), cholesterol 0-5.19* mmol/L, creatinine 59-104* µmol/L, C-reactive protein (CRP) 0-5*milligram (mg)/L,Gamma Glutamyl Transferase (GGT) 4.1-5.9*mmol/L, high density lipoproteins (HDL) cholesterol 0.99-2.32*mmol/L, potassium 3.5-5.1*mmol/L, low density lipoproteins (LDL) cholesterol 0-3.3*mmol/L, protein 66-83*g/L, sodium 136-146 * mmol/L, triglycerides 0-2.25 * mmol/L, glucose 4.1-5.9*mmol/L, and urea 2.8-7.2*mmol/L. Values below these ranges were considered as low and above these ranges were considered as high. Data for participants from any visit post-screening with values > reference range high and < reference range low are reported.
Casts, Round Epithelial Cells (REC), Squamous Epithelial Cells (SEC), Urine Erythrocytes and Urine Leukocytes at Indicated Time Points
Time frame: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urinalysis included microscopic examination parameters like Casts, REC, SEC, Urine erythrocytes and Urine leukocytes. Data at indicated time points were reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). NA indicates standard deviation could not be calculated as only 1 participant was analyzed at the given time point.
Ketones and Urine Glucose at Indicated Time Points
Time frame: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urinalysis included parameters like ketones and urine glucose. Data at indicated time points were reported.
Occult Blood at Indicated Time Points
Time frame: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urinalysis included parameter like Occult blood. Data at indicated time points were reported.
Urine Protein at Indicated Time Points
Time frame: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urinalysis included parameter like Urine protein. Data at indicated time points were reported.
Specific Gravity at Indicated Time Points
Time frame: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urinalysis included parameter like specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
Urine Potential of Hydrogen (pH) at Indicated Time Points
Time frame: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Number of Participants With Abnormal Electrocardiograms (ECG) Findings Worst Case Post-Baseline
Time frame: Up to Day 32
Single measurements of 12-lead ECGs were obtained after 10 minutes of rest in a semi-supine position for the participant. Participants with abnormal ECG findings that are clinically not significant (NCS) and clinically significant (CS) data has been presented here. The data of worst case post-Baseline is presented here.
40 secondary outcomes
Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 1
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 1
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Partial Area Under the Concentration-time Curve to Time t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 1
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Clearance (CL) of GSK1795091 for Part 1
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Volume of Distribution of GSK1795091 for Part 1
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Tumor Necrosis Factor (TNF)-Alpha From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Interferon (IFN)-Gamma From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Inducible Protein (IP)-10 From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of Monocyte Chemotactic Protein 1 (MCP-1) From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Colony Stimulating Factor 2 (GCSF) From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Interleukin 1 Receptor Antagonist (IL-1Ra) From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Interleukin 10 (IL-10) From Baseline for Part 1
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Change From Baseline in WBC Differential for Part 1
Time frame: Baseline, 4, 24 and 144 hours
Change From Baseline in CRP for Part 1
Time frame: Baseline, Days 2, 4 and 7
Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Partial Area Under the Concentration-time Curve to Time = t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Area Under the Concentration-time Curve (AUC) Time Curve for a Dosing Interval (AUC[0-tau]), AUC (0-last) of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Clearance (CL) of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Volume of Distribution of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Accumulation Ratio of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Time Invariance of GSK1795091 for Part 2
Time frame: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of TNF-alpha From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IFN-gamma From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IP-10 From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of MCP-1 From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of GCSF From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IL-1Ra From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Percentage Fold Change of Concentration of IL-10 From Baseline for Part 2
Time frame: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
Change From Baseline in WBC Differential for Part 2
Time frame: Baseline, 2, 24 and 144 hours
Number of Participants With Urinalysis Parameters Outside Reference Range for Part 2
Time frame: Up to Day 7
Number of Participants With Hematology Parameters Outside Reference Range in Part 2
Time frame: Up to Day 7
Number of Participants With Clinical Chemistry Parameters Outside Reference Range in Part 2
Time frame: Up to Day 7
Change From Baseline in CRP for Part 2
Time frame: Baseline and Pre-dose, 1, 2, 4, 8, 12, 16, 24, and 48 hours post dose
Change From Baseline in Body Temperature for Part 2
Time frame: Baseline and up to Day 7
Change From Baseline in SBP and DBP for Part 2
Time frame: Baseline and up to Day 7
Change From Baseline in Respiratory Rate for Part 2
Time frame: Baseline and up to Day 7
Change From Baseline in Pulse Rate for Part 2
Time frame: Baseline and up to Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32739049Hug 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.
- Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK1795091 in people with Cancer and Neoplasms, run by GlaxoSmithKline at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE) (time frame: Up to Day 32). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02798978, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.