A 12-Day Randomized, Blinded, Vehicle and Active Comparator-Controlled Study to Determine the Efficacy and Safety of Six Concentrations of Topical E6201 Gel in Subjects With Psoriasis Vulgaris

Phase 2

Completed

• Conditions: Psoriasis Vulgaris
• Interventions: Drug: 0.03% E6201; Drug: 0.005% E6201; Drug: 0.1% E6201; Drug: 0.01% E6201; Drug: 0.05% E6201; Drug: 0.2% E6201; Other: Placebo - 0.03% gel vehicle; Other: Placebo - 0.05% gel vehicle; Other: Placebo - 0.01% gel vehicle; Other: Placebo - 0.1% gel vehicle; Other: Placebo - 0.2% gel vehicle; Drug: Calcipotriene

• Registration Number: NCT01268527
• Lead Sponsor: Eisai Limited

Brief Summary

The purpose of this study is to investigate the efficacy, safety, tolerability and the concentration/response relationship of E6201 in subjects with psoriasis vulgaris.

Detailed Description

This is a single center, randomized, blinded, intra-individual comparison in two sequential cohorts of 15 subjects each (30 subjects in total) in an outpatient setting, in which each subject simultaneously receives five topical treatments (3 active, 1 vehicle, and 1 positive control) within one or two psoriatic plaques. Treatments consisted of 3 concentrations of E6201 gel, a negative control (gel vehicle), and a positive control (0.005% calcipotriene cream). The different concentrations of E6201 gel and vehicle control were double-blinded, while the calciprotriene cream was single-blinded. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.

Study Timeline

• Study Start: 2010-03-15
• Study First Submitted: 2010-11-15
• Primary Completion: 2010-12-11
• Study Completion: 2010-12-11
• Study First Submitted QC: 2010-12-29
• Study First Posted: 2010-12-31
• Disposition First Submitted: 2013-05-21
• Disposition First Submitted QC: 2013-05-21
• Disposition First Posted: 2013-05-29
• Results First Submitted: 2018-10-31
• Status Verified: 2021-05
• Results First Submitted QC: 2021-05-18
• Last Update Submitted: 2021-05-18
• Results First Posted: 2021-06-11
• Last Update Posted: 2021-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	0.03% E6201	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 2	Placebo - 0.01% gel vehicle	Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.
Cohort 1	Placebo - 0.03% gel vehicle	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 1	Placebo - 0.2% gel vehicle	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 2	0.05% E6201	Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.
Cohort 1	0.1% E6201	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 2	0.005% E6201	Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.
Cohort 2	0.01% E6201	Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.
Cohort 1	0.2% E6201	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 1	Placebo - 0.1% gel vehicle	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 2	Placebo - 0.05% gel vehicle	Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.
Cohort 1	Calcipotriene	Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2.
Cohort 2	Calcipotriene	Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.

Primary Outcome Measures

Name	Time	Method
Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate	Day 0 (Baseline), Day 8 (Visit 10), and Day 12 (End of Treatment)	The AUC was based on the baseline-corrected thickness of the psoriatic infiltrate (20 megahertz (MHz) Sonographic measurement) at specified days for each treatment field calculated by applying the linear trapezoidal rule. Sonographic measurements were performed using a 20 MHz high-frequency sonograph. Serial A-scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore, exact measurement of skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent band below the entrance echo. The thickness of the echo lucent psoriatic band was determined. The thickness was measured in micrometers (um) and was denoted as T.

Secondary Outcome Measures

Name	Time	Method
Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation)	Day 12/Discontinuation (Visit 14/End of Treatment)	Psoriatic infiltrate thickness was determined by 20 MHz Sonographic measurements using a 20 MHz high-frequency sonograph. Serial-A scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore exact measurement of the skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent back below the entrance echo. The thickness of the echo lucent psoriatic band was determined. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Baseline was defined as Visit 2 (Day 0). Least Squares Means (LSM) and Confidence Intervals (CI) were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.
Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation	Day 12/Discontinuation (Visit 14/End of Treatment)	Clinical (global) assessment of the test fields was performed using a 5-point score: -1 = worsened, 0 = unchanged (no effect), 1 = slight improvement, 2 = clear improvement but not completely healed, and 3 = completely healed. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Clinically apparent differences in erythema and infiltration contributed to the global assessment. Baseline was defined as Visit 2 (Day 0).
Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8	Day 8 (Visit 10)	Psoriatic infiltrate thickness was determined by 20 MHz Sonographic measurements using a 20 MHz high-frequency sonograph. Serial-A scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore exact measurement of the skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent back below the entrance echo. The thickness of the echo lucent psoriatic band was determined. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Baseline was defined as Visit 2 (Day 0). LSM and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.
Clinical (Global) Assessment of Efficacy on Day 8	Day 8 (Visit 10)	Clinical (global) assessment of the test fields was performed using a 5-point score: -1 = worsened, 0 = unchanged (no effect), 1 = slight improvement, 2 = clear improvement but not completely healed, and 3 = completely healed. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Clinically apparent differences in erythema and infiltration contributed to the global assessment. Baseline was defined as Visit 2 (Day 0).
Overview of Treatment-Emergent Adverse Events (TEAEs)	From first dose of study treatment up to 30 days after the last dose, or until resolution, whichever came first, or up to approximately 10 months.	TEAEs were defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (baseline), or re-emerged during treatment, having been present at baseline but stopped prior to treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. Safety variables included TEAEs including skin reactions, diascopy and biopsy findings, clinical laboratory parameters, vital signs, and physical examinations. For Cohort 2, special attention was given to a close, daily monitoring of the application site for signs of skin irritation. Any suspected ecchymoses or petechiae were to be followed up with a diascopy test that was to be documented with digital photographs. Any positive diascopy test was to be followed up by biopsy for skin ultrastructural analysis (if agreed to by the participant, sponsor, and investigator). Few adverse events occurred in more than one treatment group.

Trial Locations

Locations (1)

Bioskin GmbH; 🇩🇪 Berlin, Germany