Clobetasol for Oral Graft-Versus-Host Disease

Mucosal changes were assessed by the Oral Mucositis Rating Scale. The primary endpoint was evaluated using the OMRS. Oral tissue changes are rated on a scale of 0-3 compared with normal oral tissue (0-normal/no change, 1-mild change, 2-moderate change, and 3-severe change). Total score is the sum of all OMRS items with a possible range of 0. Total score is the sum of all OMRS items with a possible range of 0-273. Lower score=more normal oral mucosa. There is no standard definition of response in this field. Definitions we used in this pilot study to grade the response to study intervention are: Progress of 25% of initial score (rounded to the closest number) on the OMRS scale. Completion (PD) is defined as an increase of 25% of initial score (rounded to the closest number). Partial Response (PR) is defined as a decrease Response (CR) is defined as a PR plus a score of 0 on the erythema and ulceration components. Stable Disease (SD) does not meet criteria for progression or response.

Time frame: At 4 weeks on active treatment

Population: 18/19 are analyzed in the Clobetasol arm/group because one participant declined participation before treatment started.

Steady-state pharmacokinetics of systemic clobetasol were assessed following a single 2 min oral rinse of 0.05% clobetasol on day 14 (1 patient collected on day 12). A noncompartmental pharmacokinetic assessment was performed using WinNonlin v5 (Pharsight Corp, Mountain View, CA) from three sampling times (pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse). Plasma concentrations of clobetasol were measured using a newly designed and validated LC-MS/MS assay, with a lower limit of quantification of 0.05 ng/mL. The maximum plasma concentrations (CMAX) were recorded as observed values and the area under the plasma-concentration time curve using all three sampling time points (AUCALL) was calculated using the Linear Trapezoidal rule.

Time frame: pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse

Population: Per protocol, pharmacokinetics testing was only done on the first 10 patients in the clobetasol group.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame: Date treatment consent signed to date off study, approximately 62 months and 12 days.

Population: 18/19 are analyzed in the Clobetasol arm/group because one participant declined participation before treatment started.

Steady-state pharmacokinetics of systemic clobetasol were assessed following a single 2 min oral rinse of 0.05% clobetasol on day 14 (1 patient collected on day 12). A noncompartmental pharmacokinetic assessment was performed using WinNonlin v5 (Pharsight Corp, Mountain View, CA) from three sampling times (pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse). Plasma concentrations of clobetasol were measured using a newly designed and validated LC-MS/MS assay, with a lower limit of quantification of 0.05 ng/mL. The maximum plasma concentrations (CMAX) were recorded as observed values and the area under the plasma-concentration time curve using all three sampling time points (AUCALL) was calculated using the Linear Trapezoidal rule.

Time frame: pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse

Population: Per protocol, pharmacokinetic testing was only done on the first 10 patients in the clobetasol group. We are reporting a calculation based on these 3 time points, not a number that can be reported at 3 discrete times.

Oral cavity dryness was assessed by an oral cavity specific quality of life questionnaire. Dryness was rated based on a 0-10 rating scale on which subjects selected a single integer. 0 = no dryness and 10 = worst dryness. A negative value indicates an increase in patient-perceived oral dryness. A positive value indicates an improvement in patient-perceived oral dryness.

Time frame: Baseline and 4 weeks on active treatment

Population: 18/19 are analyzed in the Clobetasol grp because one participant declined participation before treatment started.

Oral cavity pain was assessed by an oral cavity specific quality of life questionnaire. Pain was rated based on a 0-10 rating scale on which subjects selected a single integer. 0 = no pain and 10 = worst pain. A negative value indicates an increase in oral pain. A positive value indicates an improvement in patient-perceived oral pain.

Time frame: Baseline to Day 14 and baseline to Day 28

Population: 18/19 are analyzed in the Clobetasol grp because one participant declined participation before treatment started. Clobetasol and Placebo grps were not assessed separately at Day 28. Only those pts who completed 4 wks of active clobetasol treatment and did not have an active oral infection at the 4 week timepoint were included in the final analysis.

Oral cavity sensitivity was assessed by an oral cavity specific quality of life questionnaire. Sensitivity was rated based on a 0-10 rating scale on which subjects selected a single integer. 0 = no sensitivity and 10 = worst sensitivity. A negative value indicates an increase in oral sensitivity. A positive value indicates an improvement in patient-perceived oral sensitivity.

Time frame: Baseline and 4 weeks on active treatment

Population: 18/19 are analyzed in the Clobetasol grp because one participant declined participation before treatment started.

Peripheral blood was drawn at baseline and day 28 of clobetasol rinse use, and clobetasol levels were measured in the blood sample. Plasma concentrations of clobetasol were measured using a validated LC-MS/MS assay with a lower limit of quantification of 0.05 ng/mL. Any values below detectable limit or with no peak were adjusted to 0.

Time frame: Baseline Day 0 and Day 28

Population: 37/40 participants are included in this laboratory assessment as interpretable data was not available for 3 patient samples.

Steady-state pharmacokinetics of systemic clobetasol were assessed following a single 2 min oral rinse of 0.05% clobetasol on day 14 (1 patient collected on day 12). A noncompartmental pharmacokinetic assessment was performed using WinNonlin v5 (Pharsight Corp, Mountain View, CA) from three sampling times (pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse). Plasma concentrations of clobetasol were measured using a newly designed and validated LC-MS/MS assay, with a lower limit of quantification of 0.05 ng/mL. The maximum plasma concentrations (CMAX) were recorded as observed values and the area under the plasma-concentration time curve using all three sampling time points (AUCALL) was calculated using the Linear Trapezoidal rule.

Time frame: pre-rinse, 15-45 min post-rinse, and 90-120 min post-rinse

Population: Per protocol, pharmacokinetic testing was only done on the first 10 patients in the clobetasol group. We are reporting a calculation based on these 3 time points, not a number that can be reported at 3 discrete times.