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A randomised, adaptive design, double-blind, placebo-controlled, first-in-human, two-part study to investigate the safety, tolerability, PK and preliminary efficacy of multiple topical doses of BEN2293 in patients with mild to moderate AD.
This Protocol will be adaptive and designed to enable knowledge gained from the previous cohort to be applied to subsequent cohorts. Changes made will be within the boundaries of the adaptive elements with clear control mechanisms and guidance for staying within these boundaries.
Part A is a randomised, double-blind, placebo-controlled, sequential group study to investigate ascending multiple topical doses of BEN2293 in patients with mild to moderate AD. Patients will participate in only one cohort.
Part B is a randomised, double-blind, placebo-controlled, parallel group study to investigate up to two dose regimens of topical doses of BEN2293 administered for a maximum of 28 days in patients with mild to moderate AD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Regimen Low Dose | Experimental | Low Dose Strength |
|
| Dose Regimen High Dose | Experimental | High Dose Strength |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BEN2293 (0.25% or 1.0% w/w) or matching placebo | Drug | BEN2293 and placebo will be administered as a topical ointment. Both ointments contain the same excipients; placebo ointment has been manufactured in the same way except for the addition of 0.25% and 1.0% (w/w) BEN2293. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability assessed by means of incidence of adverse events, incidence of adverse events at the local application site, mean vital signs, mean 12-lead ECG parameters and mean safety laboratory results. | Parameters measured by prompted reporting of adverse events and scheduled safety assessments. | Up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| PK-Cmax | The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients. | Up to 28 days |
| PK-Tmax | The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alexander Thompson, MBBS | MAC Clinical Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MAC Clinical Research | Manchester | M13 9NQ | United Kingdom |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Oct 12, 2023 | |
| Reset | Apr 11, 2024 | |
| Release | Feb 27, 2025 | |
| Reset | Mar 24, 2025 | |
| Release | Apr 16, 2025 | |
| Reset | May 6, 2025 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Oct 12, 2023 | Apr 11, 2024 | |||
| Feb 27, 2025 |
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
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|
| Up to 28 days |
| PK-T1/2 | The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients. | Up to 28 days |
| PK-AUC | The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients. | Up to 28 days |
| PK- over a dosing interval (AUCт) | The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients. | Up to 28 days |
| PK - Accumulation ratio | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients | Up to 28 days |
| Time to itch reduction | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. | Up to 28 days |
| Fraction of patients achieving itch reduction | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. | Up to 28 days |
| Change from baseline in the Numerical Rating Scale (NRS) for pruritus - Worst Itch over 24 hours | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. Scale graded by 0 - no itch through to 10 - worst imaginable itch. | Up to 28 days |
| Change from baseline in the Numerical Rating Scale (NRS) for pruritus - Current Itch | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. Scale graded by 0 - no itch through to 10 - worst imaginable itch. | Up to 28 days |
| Change from baseline in Eczema Area and Severity Index (EASI) score | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. Index is graded 0 - none, absent, 1 - mild, 2 - moderate and 3 - severe. | Up to 28 days |
| Number of patients achieving improvement in Eczema Area and Severity Index (EASI) score | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. Index is graded 0 - none, absent, 1 - mild, 2 - moderate and 3 - severe. | Up to 28 days |
| Change from baseline in BSA affected by AD in treated area(s) | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. | Up to 28 days |
| Change from baseline in vIGA score | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. | Up to 28 days |
| Change from baseline in Patient Oriented Eczema Measure (POEM) | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. 7 questions based on skin condition graded between 0 - no days to 4 - everyday, with a total score of 28 being the worse. | Up to 28 days |
| Change from baseline in Dermatology Life Quality Index (DLQI) | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. Index graded from 0 - not at all to 3 - very much. The higher the score, the more quality of life is impaired. | Up to 28 days |
| Change from baseline in EQ5D score | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. | Up to 28 days |
| Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. System has questions based on Itch - Scratching Behaviour, Itch - Mood and Sleep and Itch - Interference. questions are graded from 1 - never to 5 - almost always (worse score). | Up to 28 days |
| Change from baseline in Insomnia Severity Index (ISI) | The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD. 7 questions based on quality of sleep, graded 0 - none to 4 - very severe. Total score of 28 being the worse. | Up to 28 days |
| Mar 24, 2025 |
| Apr 16, 2025 | May 6, 2025 |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |