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Lipopolysaccharide · 1 trial · 1 indication
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Cantharidin | BIOLOGICAL | 5 microliter (µL) of 0.2 percent Cantharidin solution (diluted in acetone) will be applied to all subjects on forearm by topical route. |
| Lipopolysaccharide | BIOLOGICAL | 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 Factor | BIOLOGICAL | 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 Solution | DRUG | 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. |
Inclusion Criteria: * 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 in...
Lipopolysaccharide is being studied by GSK plc as an experimental treatment for rheumatoid arthritis, an inflammatory joint condition. It is a monoclonal antibody in Phase 1 clinical development. The program has completed one Phase 1 trial, and no efficacy or approval has been established for this use.
Lipopolysaccharide is being developed by GSK plc, which trades under the ticker GSK. The company is the sponsor of the Phase 1 program evaluating the monoclonal antibody in rheumatoid arthritis. Development remains at the earliest clinical stage, with one completed Phase 1 trial and no later-stage studies recorded.
Lipopolysaccharide is in Phase 1 clinical development. One Phase 1 trial has been completed, and there are no active trials. Because it is still investigational, Lipopolysaccharide is not an approved therapy for rheumatoid arthritis or any other indication, and further clinical testing would be required before any regulatory review.
One completed Phase 1 trial has studied Lipopolysaccharide: NCT03306589, titled a Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Challenge Study on Healthy Subjects. It enrolled 12 healthy male volunteers aged 18 years and older in the United Kingdom, was randomized and controlled, and was not double blind.
Lipopolysaccharide is a monoclonal antibody, a modality in which an engineered antibody binds a specific molecular target. GSK plc is developing it for rheumatoid arthritis, an immunology indication. The specific molecular target of this antibody has not been disclosed, so its precise binding interaction and downstream inflammatory pathway are not publicly characterized.