Arthritis, RheumatoidPhase 1NCT03306589

Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Challenge Study on Healthy Subjects

A Phase 1 study testing Cantharidin, Lipopolysaccharide and Granulocyte-Macrophage Colony-Stimulating Factor in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Arthritis, Rheumatoid
What is being tested?: Cantharidin, Lipopolysaccharide and Granulocyte-Macrophage Colony-Stimulating Factor
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited Kingdom
Study dates: 11 Aug 2017to 20 Jun 2018
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 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Subjects must be 18 to 45 years of age inclusive, at the time of signing the informed consent.
Subjects who are overtly healthy as determined by medical evaluation including: medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
Body mass index (BMI) within the range 19.0-30.0 kilogram per meter square (kg/m^2) (inclusive).
All male subjects. All subjects must agree to use contraception during session 2 and refrain from donating sperm from session 2 to end of study (follow up 2 visits).
Capable of giving signed informed consent.

Who cannot join

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
A positive test for human immuno deficiency virus (HIV) antibody.
Persistent abnormal C-reactive protein/ white cell count (CRP/ WCC) levels at screening.
Abnormal liver function tests at screening. For healthy subjects: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin more than or equal to 1.5xupper limit of normal (ULN) (isolated bilirubin more than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent) at screening.
A positive pre-study drug/alcohol screen.
Current, or chronic history of (h/o): liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), anaphylaxis, and /or anaphylactoid (resembling anaphylaxis) reactions; Cardiac, respiratory or renal disease (childhood asthma can be included); Sensitivity or severe allergic responses to any of the challenge agents or cantharidin, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation; Vasovagal syncope; Surgery or significant trauma in 3 months leading to study enrolment; Relevant skin conditions (for example recent h/o eczema or recurrent eczema, keloid, skin allergies, psoriasis, atopic dermatitis, and vitiligo) which in the opinion of the investigator could pose safety issues or cause interference with study procedures; Sepsis or known coagulation disorders; Peripheral edema, lymphangitis, lymph edema, pleural or pericardial effusion; Respiratory conditions including but not limited to asthma, Chronic obstructive pulmonary disease (COPD), and bronchiectasis and any current respiratory infection.

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Presence on either forearm of tattoos, naevi, hypertrophic scars, keloids, hyper or hypo-pigmentation. Subjects with very fair skin, very dark skin, excessive hair or any skin abnormalities that may, in the opinion of the Investigator, interfere with study assessments.
Unable to refrain from the use of prescription drugs taken on an intermittent (as needed) basis or non-prescription drugs; these include non-steroidal anti-inflammatory drugs (NSAIDs), vitamins, herbal and dietary 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 Day 1 of session 1 and continuing until the final follow up visit).
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: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) or currently in a study of an investigational device.
Previous exposure to LPS in a clinical research setting. Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56-day period; Current smoker or former regular smoker within 6 months before the screening visit; Unwillingness or inability to follow the procedures outlined in the protocol.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: An Open Label Parallel Group Study to Investigate the Optimum Methodology for the Use of LPS or GM-CSF as Challenge Agents on Healthy Participants by Assessing Inflammatory Biomarkers in Cantharidin-induced Skin Blisters, Peripheral Blood, and Urine

This exploratory study aims to assess exposure of healthy subjects to systemic challenge with either LPS or GM-CSF. This will be done by measuring inflammatory mediators and cellular activation markers both in circulation and in skin blisters induced by exposure to cantharidin (an agent that causes blisters). LPS is often used to induce inflammation whereas GM-CSF is a cytokine and a key mediator in inflammatory diseases. In this 2 parts study, subjects will have 2 sessions in each part. Part I of the study is a dose-exploration phase and part II will be a continuation phase to draw more precise outcomes. In session 1, subjects will be randomized to receive either LPS or GM-CSF and will have 2 blisters induced on each forearm followed by blood draws and a blister harvest on each forearm at 24 and 48 hours post-induction. After a minimum of 14 days blister healing period, subjects will return for session 2. In part I, Up to 6 cohorts will be tested and all cohorts will have 2 sessions. For Part I, initially Cohort 1 will proceed with session 1. After their blister healing period, Cohort 1 will return for their session 2 visit in two groups (Group A and Group B) on different days. Group A will be dosed on the same day (one with LPS and one with GM-CSF) and Group B will be dosed on a different day (one with LPS and one with GM-CSF) after group A. Dose-escalation in Cohort 2-6 will be continued until the well tolerated dose has been determined. The same dose will be administered to an additional Cohort in Part II and the same 2-session design will be used. Approximately 24-30 healthy subjects will be enrolled for the study and the total duration of the study for each subject will be approximately 13 weeks from screening to follow up.

Conditions: Arthritis, Rheumatoid
Being tested: Cantharidin, Lipopolysaccharide, Granulocyte-Macrophage Colony-Stimulating Factor, Saline Solution
Keywords: Inflammation, GM-CSF, LPS, Skin blisters, Healthy subjects, cantharidin
Medical subject headings: Arthritis, Rheumatoid, Inflammation, Blister

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CantharidinBiological
5 microliter (µL) of 0.2 percent Cantharidin solution (diluted in acetone) will be applied to all subjects on forearm by topical route.
LipopolysaccharideBiological
0.5 to 4 ng/kg body weight of LPS formulated as suspension in normal saline will be administered to randomized subjects via intravenous (IV) route in dose-escalation manner.
Granulocyte-Macrophage Colony-Stimulating FactorBiological
5 to 15 µg/kg of GM-CSF will be administered to randomized subjects via subcutaneous (SC) route in the abdominal region in dose-escalation manner.
Saline SolutionDrug
0.9 percent sodium chloride will be administered via IV route to all subjects at a rate of 250 mL/hour for 4 hours prior to dosing with LPS and 8 hours after dosing with LPS.

Study groups in NCT03306589
Study group	Role	What they receive
Subjects receiving LPS: Part I and Part II	Experimental	Eligible subjects will be randomized to receive LPS in a dose-escalation manner ranging from 0.5 nanogram (ng)/kg to 4 ng/kg. Subjects will be hydrated prior to administration of LPS with normal saline at a rate of 250 mL/hour for 4 hours prior to dosing and 8 hours after dosing. Receives: Biological: Cantharidin; Biological: Lipopolysaccharide; Drug: Saline Solution
Subjects receiving GM-CSF: Part I and Part II	Experimental	Eligible subjects will be randomized to receive GM-CSF in a dose-escalation manner ranging from 5 to 15 microgram (µg)/kg. Receives: Biological: Cantharidin; Biological: Granulocyte-Macrophage Colony-Stimulating Factor

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: Tumor Necrosis Factor (TNF) Alpha and Interleukin (IL) 6 for LPS Arm
Blood samples were collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Each session was for three days. NA indicates that data was not available as standard deviation could not be calculated for a single participant. All participants who were randomized to receive the treatment (LPS or GM-CSF challenge) and received one dose of challenge agent were included in Safety Population.
Measured: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes,5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Primary Soluble Inflammatory Mediators : Urinary Tetranor Prostaglandin D Metabolite (PGDM) LPS Arm
The post-challenge urine samples were collected during session 2 after LPS challenge. In session 2, participants were encouraged to pass urine immediately before LPS challenge dose and urine voids were collected from after LPS until 12 hours post-LPS and the time of the urine collection were recorded as post-challenge 1 to 11. These samples were collected for measurement of tetranor-PGDM. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. The data for normalized Tetranor PGDM was normalized by (Tetranor PGDM [pg/mL] divided by Creatinine [milligram per deciliter]) multiplied by 100. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session 2 Day 1
Part 2: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: TNF Alpha and IL 6: LPS Arm
Blood samples were planned to be collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline Primary Soluble Inflammatory Mediators : Urinary Tetranor PGDM: LPS Arm
Urine samples were planned to be collected for analysis. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2 Day 1
Part 1: Change From Baseline in White Blood Cell Numbers in Blood: GM-CSF
Blood samples were collected at indicated time-points for analysis of white blood cells. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in White Blood Cell Numbers in Blood: GM-CSF
Blood samples were planned to be collected at indicated time-points for analysis of white blood cells. Baseline value is Session 2 Day 1. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

Secondary outcomes (30)

Part 1: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister
Blister samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like IL-1 beta (b), Interferon-gamma (INFg), IL-6, IL-2, IL-8, Monocyte chemotactic protein-1 (MCP-1) and TNF-alpha. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline; Session1: 48 hours on Day3; Session 2: 24 hours on Day 2 and 48 hours on Day 3
Part 2: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister
Blister samples were planned to be collected at indicated time-points for the analysis of soluble inflammatory mediators like IL-1 beta, INFg, IL-6, IL-2, IL-8, MCP-1 and TNF-alpha. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline; Session1: 48 hours Day3; Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1: Absolute Values of Blister Volume
Blister samples were collected at indicated time-points for analysis of blister volumes. . Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline.
Measured: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 2: Absolute Values of Blister Volume
Blister samples were planned to be collected at indicated time-points for analysis of blister volumes. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 1: Change From Baseline in Cell Numbers in Blister
Blister samples were collected at indicated time-points for analysis of white blood cell in blister. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 2: Change From Baseline in Cell Numbers in Blister
Blood samples were planned to be collected at indicated time-points for analysis of white blood cell in blister. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blister
Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for monocytes in blister. Activation markers included Cluster of Differentiation (CD) 16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and Human Leukocyte Antigen - antigen D Related (HLA-DR). Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blister
Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Monocytes in Blister
Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for monocytes in blister like CD40+/CD80+. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Monocytes in Blister
Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blister
Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blister. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline; Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blister
Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Dendritic Cells in Blister
Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blister like CD40+/CD80+. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Dendritic Cells in Blister
Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Macrophages in Blister
Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for macrophages in blister. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Macrophages in Blister
Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Macrophages in Blister
Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blister like CD40+/CD80+. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Macrophages in Blister
Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline in Soluble Inflammatory Mediators in Blood
Blood samples were collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like IL-1 beta, INFg, IL-2, IL-8, and MCP-1 in blood. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Measured: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2:Change From Baseline in Soluble Inflammatory Mediators in Blood
Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Soluble Inflammatory Mediators in Blood: TNF-alpha, IL-6 and GM-CSF: GM-CSF Arm
Blood samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like TNF-alpha, IL-6 and GM-CSF in blood. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Soluble Inflammatory Mediators in Blood: TNF-alpha, IL-6 and GM-CSF for GM-CSF Arm
Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Soluble Inflammatory Mediators in Blood: C-reactive Protein (CRP)
Blood samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like CRP in blood. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline; Session 2: Post challenge Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Soluble Inflammatory Mediators in Blood: CRP
Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline; Session 2: Post challenge Day 1; Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blood
Blood samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for monocytes in blood. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blood
Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2: 40 minutes, 2 hour 40 minutes, 5 hour 40 minutes,9hours 40 minutes on Day 1; Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blood
Blood samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blood. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blood
Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Circulating Leukocyte Numbers in Blood: LPS Arm
Blood samples were collected at indicated time-points for analysis of leukocyte. Latest pre-challenge assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Measured: Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Circulating Leukocyte Numbers in Blood: LPS Arm
Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Measured: Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Aug 201720 Jun 2018

First posted11 Oct 2017
Study start11 Aug 2017
Primary completion3 Jan 2018
Study completion20 Jun 2018

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.
Other trials for Arthritis, RheumatoidStudies 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: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Model description: Subjects in 2 separate groups will be randomized to receive either LPS or GM-CSF at the same time.
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03306589
Sponsor's protocol ID: 207654
Status last verified: Jun 2019
First submitted: 11 Jul 2017
Last updated: 8 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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See locations

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All Arthritis, Rheumatoid trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label Parallel Group Study to Investigate the Optimum Methodology for the Use of LPS or GM-CSF as Challenge Agents on Healthy Participants by Assessing Inflammatory Biomarkers in Cantharidin-induced Skin Blisters, Peripheral Blood, and Urine
ClinicalTrials.gov ID: NCT03306589
Acronym / sponsor ID: 207654
Conditions: Arthritis, Rheumatoid
Keywords: Inflammation, GM-CSF, LPS, Skin blisters, Healthy subjects, cantharidin
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 11 Aug 2017 (actual)
Primary completion: 3 Jan 2018 (actual)
Study completion: 20 Jun 2018 (actual)
First posted: 11 Oct 2017 (actual)
Results: Posted 8 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Subjects in 2 separate groups will be randomized to receive either LPS or GM-CSF at the same time.

Arm	Type	Receives
Subjects receiving LPS: Part I and Part II	Experimental	Biological: Cantharidin, Biological: Lipopolysaccharide, Drug: Saline SolutionEligible subjects will be randomized to receive LPS in a dose-escalation manner ranging from 0.5 nanogram (ng)/kg to 4 ng/kg. Subjects will be hydrated prior to administration of LPS with normal saline at a rate of 250 mL/hour for 4 hours prior to dosing and 8 hours after dosing.
Subjects receiving GM-CSF: Part I and Part II	Experimental	Biological: Cantharidin, Biological: Granulocyte-Macrophage Colony-Stimulating FactorEligible subjects will be randomized to receive GM-CSF in a dose-escalation manner ranging from 5 to 15 microgram (µg)/kg.

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Subjects must be 18 to 45 years of age inclusive, at the time of signing the informed consent.
Subjects who are overtly healthy as determined by medical evaluation including: medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
Body mass index (BMI) within the range 19.0-30.0 kilogram per meter square (kg/m^2) (inclusive).
All male subjects. All subjects must agree to use contraception during session 2 and refrain from donating sperm from session 2 to end of study (follow up 2 visits).
Capable of giving signed informed consent.

Key exclusion criteria (10 listed)

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
A positive test for human immuno deficiency virus (HIV) antibody.
Persistent abnormal C-reactive protein/ white cell count (CRP/ WCC) levels at screening.
Abnormal liver function tests at screening. For healthy subjects: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin more than or equal to 1.5xupper limit of normal (ULN) (isolated bilirubin more than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent) at screening.
A positive pre-study drug/alcohol screen.

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
Cantharidin5 microliter (µL) of 0.2 percent Cantharidin solution (diluted in acetone) will be applied to all subjects on forearm by topical route.	Biological	Subjects receiving GM-CSF: Part I and Part II, Subjects receiving LPS: Part I and Part II
Lipopolysaccharide0.5 to 4 ng/kg body weight of LPS formulated as suspension in normal saline will be administered to randomized subjects via intravenous (IV) route in dose-escalation manner.	Biological	Subjects receiving LPS: Part I and Part II
Granulocyte-Macrophage Colony-Stimulating Factor5 to 15 µg/kg of GM-CSF will be administered to randomized subjects via subcutaneous (SC) route in the abdominal region in dose-escalation manner.	Biological	Subjects receiving GM-CSF: Part I and Part II
Saline Solution0.9 percent sodium chloride will be administered via IV route to all subjects at a rate of 250 mL/hour for 4 hours prior to dosing with LPS and 8 hours after dosing with LPS.	Drug	Subjects receiving LPS: Part I and Part II

Primary outcome

Part 1: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: Tumor Necrosis Factor (TNF) Alpha and Interleukin (IL) 6 for LPS Arm
Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes,5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Blood samples were collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Each session was for three days. NA indicates that data was not available as standard deviation could not be calculated for a single participant. All participants who were randomized to receive the treatment (LPS or GM-CSF challenge) and received one dose of challenge agent were included in Safety Population.
Part 1: Change From Baseline in Primary Soluble Inflammatory Mediators : Urinary Tetranor Prostaglandin D Metabolite (PGDM) LPS Arm
Time frame: Baseline, Session 2 Day 1
The post-challenge urine samples were collected during session 2 after LPS challenge. In session 2, participants were encouraged to pass urine immediately before LPS challenge dose and urine voids were collected from after LPS until 12 hours post-LPS and the time of the urine collection were recorded as post-challenge 1 to 11. These samples were collected for measurement of tetranor-PGDM. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. The data for normalized Tetranor PGDM was normalized by (Tetranor PGDM [pg/mL] divided by Creatinine [milligram per deciliter]) multiplied by 100. NA indicates that data was not available as standard deviation could not be calculated for a single participant.
Part 2: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: TNF Alpha and IL 6: LPS Arm
Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Blood samples were planned to be collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Part 2: Change From Baseline Primary Soluble Inflammatory Mediators : Urinary Tetranor PGDM: LPS Arm
Time frame: Baseline, Session 2 Day 1
Urine samples were planned to be collected for analysis. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.
Part 1: Change From Baseline in White Blood Cell Numbers in Blood: GM-CSF
Time frame: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Blood samples were collected at indicated time-points for analysis of white blood cells. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.
Part 2: Change From Baseline in White Blood Cell Numbers in Blood: GM-CSF
Time frame: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Blood samples were planned to be collected at indicated time-points for analysis of white blood cells. Baseline value is Session 2 Day 1. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

30 secondary outcomes

Part 1: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister
Time frame: Baseline; Session1: 48 hours on Day3; Session 2: 24 hours on Day 2 and 48 hours on Day 3
Part 2: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister
Time frame: Baseline; Session1: 48 hours Day3; Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1: Absolute Values of Blister Volume
Time frame: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 2: Absolute Values of Blister Volume
Time frame: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 1: Change From Baseline in Cell Numbers in Blister
Time frame: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 2: Change From Baseline in Cell Numbers in Blister
Time frame: Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3
Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Monocytes in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Monocytes in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blister
Time frame: Baseline; Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Dendritic Cells in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Dendritic Cells in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Macrophages in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Macrophages in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Macrophages in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Macrophages in Blister
Time frame: Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3
Part 1:Change From Baseline in Soluble Inflammatory Mediators in Blood
Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2:Change From Baseline in Soluble Inflammatory Mediators in Blood
Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Soluble Inflammatory Mediators in Blood: TNF-alpha, IL-6 and GM-CSF: GM-CSF Arm
Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Soluble Inflammatory Mediators in Blood: TNF-alpha, IL-6 and GM-CSF for GM-CSF Arm
Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Soluble Inflammatory Mediators in Blood: C-reactive Protein (CRP)
Time frame: Baseline; Session 2: Post challenge Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Soluble Inflammatory Mediators in Blood: CRP
Time frame: Baseline; Session 2: Post challenge Day 1; Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blood
Time frame: Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blood
Time frame: Baseline, Session 2: 40 minutes, 2 hour 40 minutes, 5 hour 40 minutes,9hours 40 minutes on Day 1; Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blood
Time frame: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blood
Time frame: Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Circulating Leukocyte Numbers in Blood: LPS Arm
Time frame: Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 2: Change From Baseline in Circulating Leukocyte Numbers in Blood: LPS Arm
Time frame: Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

Results and safety

Results posted to the registry on 8 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: LPS 0.5 ng/kg	2	2
Part 1: LPS 0.75 ng/kg	4	4
Part 1: LPS 1 ng/kg	2	2
Part 1: GM-CSF 60 µg/m^2	4	4
Part 2: Participants With LPS	0	0
Part 2: Participants With GM-CSF	0	0

Primary outcome: Part 1: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: Tumor Necrosis Factor (TNF) Alpha and Interleukin (IL) 6 for LPS Arm

Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes,5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3. Mean (Standard Deviation). Unit: Picograms per milliliter

Measure	Part 1: LPS 0.5 ng/kg n = 2	Part 1: LPS 0.75 ng/kg n = 4	Part 1: LPS 1 ng/kg n = 2
IL-6, Session2,Day1, -5 minutes, n=2, 4, 2	2.4086 (0.09467)	0.2798 (0.12546)	-0.0126 (0.01785)
IL-6, Session2,Day1, 10 minutes, n=2, 4, 2	3.6460 (2.68681)	0.2450 (0.16048)	0.0123 (0.01746)
IL-6, Session2,Day1, 25 minutes, n=1, 4, 2	3.3141 (NA)	1.3623 (0.88290)	1.8854 (0.15615)
IL-6, Session2,Day1, 40 minutes, n=2, 4, 2	10.8074 (9.22779)	8.7622 (8.41234)	11.8672 (3.39867)
IL-6, Session2,Day1, 1 hour 10 minutes, n=2, 4, 2	30.6395 (26.77767)	81.0629 (104.23961)	51.8232 (22.59507)
IL-6, Session2,Day1, 1 hour 40 minutes, n=2, 4, 2	41.3221 (35.42047)	193.7107 (218.97996)	65.5675 (36.08430)
IL-6, Session2,Day1, 2 hour 40 minutes, n=2, 4, 2	23.9321 (21.46574)	133.2063 (92.47028)	32.3842 (25.56374)
IL-6, Session2,Day1, 5 hour 40 minutes, n=2, 4, 2	5.6991 (0.68051)	2.5645 (1.20737)	4.5141 (2.09962)

Population analysed: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Primary outcome: Part 1: Change From Baseline in Primary Soluble Inflammatory Mediators : Urinary Tetranor Prostaglandin D Metabolite (PGDM) LPS Arm

Time frame: Baseline, Session 2 Day 1. Mean (Standard Deviation). Unit: Picograms per milligram

Measure	Part 1: LPS 0.5 ng/kg n = 2	Part 1: LPS 0.75 ng/kg n = 4	Part 1: LPS 1 ng/kg n = 2
Session2, Day1,Post challenge1, n=2, 4, 2	73.846 (116.0073)	-85.080 (226.4168)	134.806 (166.6716)
Session2, Day1,Post challenge 2, n=2, 4, 2	99.438 (112.5337)	88.984 (155.1855)	276.788 (134.7190)
Session2, Day1,Post challenge 3, n=2, 4, 2	32.006 (88.2367)	25.390 (181.8009)	200.337 (183.9484)
Session2, Day1,Post challenge 4, n=2, 4, 2	-119.091 (304.0503)	-68.209 (262.6169)	140.482 (108.7880)
Session2, Day1,Post challenge 5, n=1, 4, 2	112.355 (NA)	-146.294 (165.8587)	184.263 (262.9020)
Session2, Day1,Post challenge 6, n=0, 4, 1	–	-202.918 (197.6455)	-125.839 (NA)
Session2, Day1,Post challenge 7, n=0, 4, 1	–	-227.544 (226.2006)	6.336 (NA)
Session2, Day1,Post challenge 8, n=0, 3, 1	–	-144.855 (53.7768)	-117.672 (NA)

Population analysed: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Primary outcome: Part 2: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: TNF Alpha and IL 6: LPS Arm

Time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

Population analysed: Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Primary outcome: Part 2: Change From Baseline Primary Soluble Inflammatory Mediators : Urinary Tetranor PGDM: LPS Arm

Time frame: Baseline, Session 2 Day 1

Population analysed: Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

30 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until 69 days in Part 1 of the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: LPS 0.5 ng/kg	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Part 1: LPS 0.75 ng/kg	0 of 4 (0%)	4 of 4 (100%)	0 of 4
Part 1: LPS 1 ng/kg	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Part 1: GM-CSF 60 µg/m^2	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Part 2: Participants With LPS	0 of 0	0 of 0	0
Part 2: Participants With GM-CSF	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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 Cantharidin, Lipopolysaccharide and Granulocyte-Macrophage Colony-Stimulating Factor in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 1 site in United Kingdom.

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 5 inclusion and 10 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 8 Aug 2019. 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 United Kingdom. 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 8 Aug 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?

Part 1: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: Tumor Necrosis Factor (TNF) Alpha and Interleukin (IL) 6 for LPS Arm (time frame: Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes,5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3). The study lists 6 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 NCT03306589.

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 8 Aug 2019.