Adapalene 0.3% - Benzoyl Peroxide 2.5% Gel and Risk of Formation of Atrophic Acne Scars

Study Overview
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Brief Summary
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This was a multi-centre, randomized, investigator blinded, vehicle controlled trial using intra-individual comparison (right half-face versus left half-face). Participants with each half-face randomized to one of the two following treatments: Adapalene 0.3 percent (%) - benzoyl peroxide (BPO) 2.5% gel (TactuPump® Forte). Vehicle gel The main objective of this trial was to evaluate the effect of Adapalene 0.3% - BPO 2.5% (ABPO Forte) gel versus vehicle gel on the risk of formation of atrophic acne scars in moderate to severe acne participants.

Official Title
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Effect of Adapalene 0.3% - Benzoyl Peroxide 2.5% Gel Versus Vehicle Gel on the Risk of Formation of Atrophic Acne Scars in Moderate to Severe Acne Subjects

Conditions
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Acne Vulgaris, Atrophic Acne Scars

Intervention / Treatment
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* Drug: ABPO Forte Gel
* Drug: Vehicle gel


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Participants with clinical diagnosis of moderate to severe acne vulgaris on the face defined by: Investigator's Global Assessment score of 3 or 4, with same score on both sides; and A minimum of 25 inflammatory lesions (papules and pustules) in total, with at least 10 on each side (excluding the nose); and No more than two acne nodules (less than or equal to [>=] 1 centimeter [cm]); and A minimum of 10 atrophic acne scars in total (upper than 2 millimeters [mm]) (excluding the nose) Participants with a symmetric number of both inflammatory and non-inflammatory lesions on the whole face, and atrophic acne scars on the whole face. Participants with skin phototype of I to IV on Fitzpatrick's scale. Main Exclusion Criteria: Participants with acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne, etc.), nodulo cystic acne, acne requiring systemic treatment. Prior failure to treatment with TactuPump® Forte (Adapalene 0.3% - BPO 2.5%). Participants with more than 3 excoriated acne lesions. Participants with skin abraded on the treated area or affected by eczema, seborrhoeic dermatitis, cuts or sunburn. Female participant who is pregnant, nursing or planning a pregnancy during the trial or within one month after the last trial treatment application. Male participant with a beard or facial hair, which would interfere with the clinical trial evaluations or clinical trial procedures. Participants having received at least one of the following topical treatments on the treated area: Corticosteroids, antibiotics, benzoyl peroxide, azelaic acid, hydroxyacids, Zinc containing treatments, antibacterials, antiseptics, other anti-inflammatory drugs or other acne treatments (2 weeks); Retinoids (4 weeks); Cosmetic/aesthetic procedures on the face (1 week); Photodynamic therapy, laser therapy, microdermabrasion for acne (3 months). Participants having received at least one of the following systemic treatments: Corticosteroids (except locally acting corticosteroids such as inhaled or intrathecal or dermal application at distance from the face), antibiotics (except penicillin) (1 month); Spironolactone (3 months) / Drospirenone (3 months, unless dose is stable since at least 3 months); Oral retinoids (6 months); Cyproterone acetate / Chlormadinone acetate (6 months); Immunomodulators (3 months).

Ages Eligible for Study
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Minimum Age: 16 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: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: ABPO Forte Gel<br> | Drug: ABPO Forte Gel<br>* Participants applied Adapalene 0.3% - Benzoyl peroxide (BPO) 2.5% gel (ABPO Forte) topically to the affected areas once daily for 24 weeks in Part 1 and for 48 weeks in Part 2.<br>* Other names: TactuPump Forte;|
| Placebo Comparator: Part 1: ABPO Forte Vehicle Gel<br> | Drug: Vehicle gel<br>* Participants applied placebo matched to ABPO Forte gel topically to the affected areas once daily for 24 weeks in Part 1 and 48 weeks in Part 2.<br>|
| Experimental: Part 2: ABPO Forte Gel<br> | Drug: ABPO Forte Gel<br>* Participants applied Adapalene 0.3% - Benzoyl peroxide (BPO) 2.5% gel (ABPO Forte) topically to the affected areas once daily for 24 weeks in Part 1 and for 48 weeks in Part 2.<br>* Other names: TactuPump Forte;|
| Placebo Comparator: Part 2: ABPO Forte Vehicle Gel<br> | Drug: Vehicle gel<br>* Participants applied placebo matched to ABPO Forte gel topically to the affected areas once daily for 24 weeks in Part 1 and 48 weeks in Part 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Total Atrophic Acne Scar Count Per Half-face | The scars were counted according to their size defined in two categories using 2-millimeter (mm) and 4-mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars greater than (>) 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. To obtain the total number of atrophic scars per half-face, atrophic acne scar counts for each half-face was added. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Total Atrophic Acne Scar Count Per Half-face at Each Post-baseline Visit | The scars were counted according to their size defined in two categories using 2 mm and 4 mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars > 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. To obtain the total number of atrophic scars per half-face, atrophic acne scar counts for each half-face was added. | Part 1: Weeks 1, 4, 8, 12, 16 and 20; Part 2: Weeks 1, 4, 8, 12, 16, 20, 36 and 48 | 
| Part 1 and Part 2: Percent Change From Baseline in Total Atrophic Acne Scar Count Per Half-face at Each Post-baseline Visit | The scars were counted according to their size defined in two categories using 2 mm and 4 mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars > 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. | Part 1: Weeks 1, 4, 8, 12, 16, 20 and 24; Part 2: Weeks 1, 4, 8, 12, 16, 20, 24, 36 and 48 | 
| Part 1 and Part 2: Investigator's Scar Global Assessment (ISGA) Score | ISGA was an assessment scale used to evaluate facial acne severity. ISGA was recorded using a 5-point scale ranges from 0 to 4, where (0 = clear [No visible scars from acne); 1 = almost clear [Hardly visible scars from 50 cm away]; 2 = mild [Easily recognizable; less than half the affected face area]; 3 = moderate [More than half and less than 75% of the affected face area]; 4 = severe [More than 75% of the affected face area]) based on inflammation, pustules and papulation/infiltration. Higher score indicated severe acne. | Part 1: Weeks 1, 4, 8, 12, 16, 20 and 24; Part 2: Weeks 1, 4, 8, 12, 16, 20, 24, 36 and 48 | 
| Part 1: Percentage of Participants With Investigator's Preference on Overall Scar Severity | The investigator rated their preference on a scale ranging from -2 (left side a lot better than right) to 2 (right side a lot better than left). Overall scar severity was assessed using a 5-point scale where (-2 = Left a lot better than right; -1 = Left a little bit better than right; 0 = No preference; 1 = Right a little bit better than left; 2 = Right a lot better than left. ABPO forte was applied on left side and vehicle gel was applied on right side. | At Week 12 and Week 24 | 
| Part 1 and Part 2: Percent Change From Baseline in Total Lesion Count Per Half-face at Each Post-baseline Visit | Total lesion counts corresponded to the sum of inflammatory and non-inflammatory lesions, and other lesions. The investigator counted all inflammatory lesions (papules and pustules), non-inflammatory lesions (open and closed comedone) and other lesions (nodules) for each half-face. | Part 1: Weeks 1, 4, 8, 12, 16 and 20; Part 2: Weeks 1, 4, 8, 12, 16, 20, 36 and 48 | 
| Part 1 and Part 2: Percent Change From Baseline in Inflammatory Lesion Count Per Half-face at Each Post-baseline Visit | Inflammatory lesions included papules and pustules. Papule is a small, solid elevation less than one centimeter in diameter. Most of the lesion is above the surface of the skin. Pustule is a small, circumscribed elevation of the skin which contains yellow-white exudates. | Part 1: Weeks 1, 4, 8, 12, 16, 20 and 24; Part 2: Weeks 1, 4, 8, 12, 16, 20, 24, 36 and 48 | 
| Part 1 and Part 2: Percent Change From Baseline in Non-inflammatory Lesion Count Per Half-face at Each Post-baseline Visit | Non-inflammatory lesions included open comedone and closed comedone. Open comedone is a mass of sebaceous material that is impacted behind an open follicular orifice (blackhead). Closed comedone is a mass of sebaceous material that is impacted behind a closed follicular orifice (white head). | Part 1: Weeks 1, 4, 8, 12, 16, 20 and 24; Part 2: Weeks 1, 4, 8, 12, 16, 20, 24, 36 and 48 | 
| Part 1 and Part 2: Investigator's Global Assessment (IGA) Score Per Half-face at Each Post-baseline Visit | IGA is an assessment scale used to determine severity of acne and clinical response to treatment on a 5-point scale (0 = clear [Clear skin with no inflammatory or non inflammatory lesions]; 1= almost clear [A few scattered comedones and a few small papules]; 2= mild [Easily recognizable; less than half the face is involved. Some comedones and some papules and pustules]; 3= moderate [More than half of the face is involved. Many comedones, papules and pustules. One small nodule may be present] and 4= severe [Entire face is involved. Covered with comedones, numerous papules and pustules. Few nodules may or may not be present]) based on erythema and papulation/ infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). | Part 1: Weeks 1, 4, 8, 12, 16, 20 and 24; Part 2: Weeks 1, 4, 8, 12, 16, 20, 24, 36 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acne, scars