Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Cantharidin · 2 trials · 2 indications
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.
Volume of fluid extracted from blisters induced by cantharidin application
Flow cytometry performed on cells from blister fluid including measurement of some or all of the following parameters: CD45, CD16, CD14, cell viability, CD206, CD64 or CD84, apoptosis, total blister leukocytes (CD45+), monocytes (CD14+), neutrophils (CD16 high), monocyte/macrophage like cells (CD64+ or CD84+); subsets of these cells that are undergoing apoptosis; subsets of monocyte/macrophages
Inflammatory mediators in blister fluid, measured by immunoassay as primary endpoints may include (but will not be limited to): MPO, IL-10, IL-8, IL-6, IL-1β, TNF-α, LTB4.
| 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. |
| Effect of Aspirin | ACTIVE_COMPARATOR | Positive control as previously used in the cantharidin blister experimental model of inflammation |
| Effect of steroid - Prednisolone | EXPERIMENTAL | Prednisolone selected as steroids should provide the most robust positive control anti-inflammatory therapy |
| Cantharidin exposure to optimise blister formation | EXPERIMENTAL | Cantharidin exposure to optimise blister formation |
| 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. |
| Cantharidin solution | DRUG | 5 microlitres of 0.025 to 0.5% topically on Day 1, 2 and 3 |
| Aspirin | DRUG | 300mg three times daily orally over a course of 4 days (starting Day -3) Part 2 only |
| Prednisolone | DRUG | 30mg orally once a day over a course of 4 days (starting Day -3) Part 2 only |
| Placebo to aspirin | DRUG | 0mg three times daily orally over a course of 4 days (starting Day -3) Part 2 only |
| Placebo to prednisolone | DRUG | 0mg orally once a day over a course of 4 days (starting Day -3) Part 2 only |
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...
Cantharidin is an investigational drug being studied for use in inflammation, arthritis, and rheumatoid arthritis. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities. The drug is being developed by GSK plc as a monoclonal antibody for immunology applications.
Cantharidin is a monoclonal antibody being developed for immunology applications. As a monoclonal antibody, it is designed to target specific components of the immune system involved in inflammatory processes. However, the specific molecular target of Cantharidin has not been disclosed in available clinical trial information.
Cantharidin is being developed by GSK plc, a global biopharmaceutical company listed on the stock exchange under the ticker symbol GSK. The drug is currently in Phase 1 clinical development for inflammatory conditions including arthritis and rheumatoid arthritis.
Cantharidin is currently in Phase 1 clinical development. It is an investigational drug and has not received regulatory approval. Clinical trials have been conducted in healthy volunteers to evaluate the drug's effects in inflammatory models, including studies related to arthritis and rheumatoid arthritis.
Cantharidin has been studied in two completed Phase 1 clinical trials. The first trial, NCT01762787, was a methodology study to validate the cantharidin blister model in healthy volunteers with inflammation. The second trial, NCT03306589, was a challenge study using lipopolysaccharide or GM-CSF in healthy subjects for arthritis and rheumatoid arthritis.
Cantharidin is the drug name used in clinical development by GSK plc. It is a monoclonal antibody, which is distinct from the naturally occurring compound cantharidin derived from blister beetles. The drug is being investigated for inflammatory conditions and is currently in Phase 1 clinical trials.