Explorative Trial Evaluating the Efficacy and Tolerability of LEO43204 in Moderate to Severe Acne

Study Overview
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Brief Summary
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An exploratory Phase 2, single, centre, prospective, randomized, placebo-controlled, double-blinded, split-pace (left/right) design trial to evaluate the efficacy and tolerability of LEO 43204 in adults with moderate to severe acne.

Official Title
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Explorative Trial Evaluating the Efficacy and Tolerability of LEO43204 Applied in a Split-face (Left/Right) Topical Design in Adults With Moderate to Severe Acne

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: LEO43204
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects should be diagnosed with acne vulgaris of the face Fitzpatrick skin types I-III (due to lack of safety data for the investigational product in darker skin types) Disease severity and total lesion count should be similar in both TAs Disease severity grade as moderate to severe according to the investigator's global assessment (grade 3-4) Age 18 to 35 years incl. Male or female Female Subjects must be of either non-childbearing potential or child-bearing potential with a confirmed negative pregnancy test Exclusion Criteria: Subjects with nodulocystic acne, acne conglobata, acne fulminans, secondary acne (e.g. chlor-acne, drug-induced acne) Subjects with previous history of keloid formation or post-inflammatory hyperpigmentation Systemic retinoids within 12 month or systemic antibiotics within 1 month before Day 1 Topical retinoids within 3 months before Day 1 or other topical treatments and/or medicated products and cosmetics that in the opinion of the investigator may influence the subjects acne vulgaris (including soaps containing antibacterial agents such as benzoyl peroxide, keratinolytic agents such as salicylic acid, skin fresheners/astringents or aftershave products) within 1 month before Day 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO43204 0,018%<br>Experimental drug | Drug: LEO43204<br> <br> |
| Placebo Comparator: Vehicle<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Lesion Count (Inflammatory and Non-inflammatory) | Total lesion count (inflammatory and non-inflammatory) in acne lesion areas. | At Week 12 (Day 84) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Lesion Count | Count of inflammatory lesions in acne lesion areas | At Week 12 (Day 84) | 
| Non-inflammatory Lesion Count | Count of non-inflammatory lesions in acne lesion areas | At Week 12 (Day 84) | 
| Number of Participants Stratified by Investigator's Global Assessment (IGA) of the Treatment Area | The IGA score was determined according to the 5 point scale below. 0=Clear skin with no inflammatory and non-inflammatory lesions Almost clear; rare non-inflammatory lesions with no more than one small inflammatory lesion Mild severity; greater than Grade 1; some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions) Moderate severity; greater than Grade 2; up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesions Severe; greater than Grade 3; up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions | At Week 12 (Day 84) | 
| Composite Local Skin Response (LSR) Score at All Visits | The Local Skin Responses consists of the following 6 components: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR component is given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. The composite LSR score (0-24) is the sum of the scores graded from 0 to 4 on all six individual LSR categories. Please see following outcome measure descriptions on the grading scale for the individual components: Erosion/ulceration: 6. Secondary outcome measure Crusting: 7. Secondary outcome measure. Erythema: 8. Secondary outcome measure. Flaking/scaling: 9. Secondary outcome measure. Swelling: 10. Secondary outcome measure. Vesiculation/pustulation: 11. Secondary outcome measure. | At baseline (Day 1), Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Participant's Component LSR Score: Erosion/Ulceration | The Erosion/Ulceration score was determined according to the 5 point scale below. 0=not present Lesion specific erosion Erosion extending beyond individual lesions Erosion >50% Black eschar or ulceration | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Participant's Component LSR Score: Crusting | The crusting score was determined according to the 5 point scale below. 0=not present isolated crusting Crusting<50% Crusting>50% Crusting extending outside treatment area | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Participant's Component LSR Score: Erythema | The erythema score was determined according to the 5 point scale below. Erythema 0=not present slightly pink <50% Pink or light red >50% Red,restricted to treatment area Red extending outside treatment area | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Participant's Component LSR Score: Flaking/Scaling | The flaking/scaling score was determined according to the 5 point scale below. 0=not present Isolated scale, specific to lesion Scale<50% Scale>50% Scaling extending outside treatment area | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Participant's Component LSR Score: Swelling | The swelling score was determined according to the 5 point scale below. 0=Not present Slight, lesion specific oedema Palpable oedema extending beyond individual lesions Confluent and/or visible oedema Marked swelling extending outside treatment area | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Participant's Component LSR Score: Vesiculation/Pustulation | The vesiculation/postulation score was determined according to the 5 point scale below. 0=not present vesicles only Transudate or pustulates with or without vesicles <50% Transudate or pustulates, with or without vesicles >50% Transudate or pustulates, with or without vesicles extending outside treatment area 4=Marked swelling extending outside treatment area | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 | 
| Number of Participants With Occurrence of Unacceptable LSR Scores or Unacceptable Safety and Tolerability Events at All Visits | Unacceptable LSRs, safety and tolerability in an individual participant were defined as: Clinically relevant signs or symptoms that in the opinion of the investigator were deemed unacceptable. Occurrence of LSRs as specified below: One of the following Grade 4 crusting Grade 4 erosion/ulceration Grade 4 vesiculation/pustulation extending significantly outside treatment areas Two of the following Grade 4 erythema Grade 3 crusting Grade 4 swelling extending significantly outside treatment areas Grade 3 erosion/ulceration Grade 3 vesiculation/pustulation | At Day 1, Day 2, Day 3, Day 4, Day 8, Week 2, Week 4, Week 8 and Week 12 |