Safety and Efficacy of AN2728 Topical Ointment, 2% in Children, Adolescents, and Adults (Aged 2 Years and Older) With Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the safety and efficacy of AN2728 Topical Ointment, 2% in children, adolescents, and adults (ages 2 years and older) with atopic dermatitis.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study of the Safety and Efficacy of AN2728 Topical Ointment, 2% in Children, Adolescents, and Adults (Ages 2 Years and Older) With Atopic Dermatitis

Conditions
-----------------
Dermatitis, Atopic

Intervention / Treatment
-----------------
* Drug: AN2728 Topical Ointment, 2%
* Drug: Matching vehicle control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females 2 years and older Has a clinical diagnosis of Atopic Dermatitis (AD) according to the criteria of Hanifin and Rajka Has AD involvement ≥ 5% Treatable %BSA (excluding the scalp) Has an ISGA score of Mild (2) or Moderate (3) at Baseline/Day 1 All female subjects of childbearing potential must use acceptable methods of contraception from the Screening Visit continuously until 30 days after stopping study drug Exclusion Criteria: As determined by the study doctor, a medical history that may interfere with study objectives Unstable AD or any consistent requirement for high potency topical corticosteroids History of use of biologic therapy (including intravenous immunoglobulin) Recent or anticipated concomitant use of systemic or topical therapies that might alter the course of AD Recent or current participation in another research study Females who are breastfeeding, pregnant, or with plans to get pregnant during the participation in the study Participation in a previous AN2728 clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 2 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AN2728 Topical Ointment, 2%<br>AN2728 Topical Ointment, 2%, applied twice daily for up to 28 days | Drug: AN2728 Topical Ointment, 2%<br> <br> |
| Placebo Comparator: Matching vehicle control<br>Matching vehicle control, applied twice daily for up to 28 days | Drug: Matching vehicle control<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug to the end of study, that were absent before treatment or that worsened relative to pre-treatment state. | AEs: Baseline (Day 1) up to Day 29, SAEs: Baseline (Day 1) up to Day 36 | 
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings at Day 8 | ECG parameters that were analyzed: PR interval, QRS interval, QT interval and corrected QT interval based on Fridericia's formula (QTcF). Clinical significance of change from baseline in ECG findings was determined by investigator. | Baseline, Day 8 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Day 36 | Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, pulse, respiratory rate and body temperature. Vital sign measurements were performed with the participant in the seated or supine position and after the participant had been calmly sitting or lying face up for a minimum of 5 minutes. Clinical significance of change from baseline value was determined by investigator. | Baseline (Day 1), Day 36 | 
| Number of Participants With Clinically Significant Laboratory Values | Laboratory values included: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Bilirubin, Blood Urea Nitrogen, Glucose, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Basophils, Eosinophils, Erythrocytes, Potassium, Protein, Sodium. Clinically significant laboratory abnormalities were defined as abnormal laboratory test values that have clinical manifestations or require medical intervention, as per investigator's discretion. | Baseline up to Day 36 | 
| Percentage of Participants With Local Tolerability Symptoms at Baseline | Local tolerability symptoms (burning/stinging) were assessed in participants at sites of study drug application. Symptoms were assessed on 4-point scale ranging from 0 to 3, where 0 = none (no stinging/burning), 1 = mild (slight warm, tingling sensation); 2= moderate (definite warm; tingling/stinging sensation that is somewhat bothersome and severe); 3= severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores indicated more severe symptoms. Percentage of participants with each level of local tolerability (none, mild, moderate, severe) symptoms were reported. | Baseline (Day 1) | 
| Percentage of Participants With Local Tolerability Symptoms at Day 8 | Local tolerability symptoms (burning/stinging) were assessed in participants at sites of study drug application. Symptoms were assessed on 4-point scale ranging from 0 to 3, where 0= none (no stinging/burning), 1 = mild (slight warm, tingling sensation); 2= moderate (definite warm; tingling/stinging sensation that is somewhat bothersome and severe); 3= severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores indicated more severe symptoms. Percentage of participants with each level of local tolerability (none, mild, moderate, severe) symptoms were reported. | Day 8 | 
| Percentage of Participants With Local Tolerability Symptoms at Day 15 | Local tolerability symptoms (burning/stinging) were assessed in participants at sites of study drug application. Symptoms were assessed on 4-point scale ranging from 0 to 3, where 0= none (no stinging/burning), 1= mild (slight warm, tingling sensation); 2= moderate (definite warm; tingling/stinging sensation that is somewhat bothersome and severe); 3= severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores indicated more severe symptoms. Percentage of participants with each level of local tolerability (none, mild, moderate, severe) symptoms were reported. | Day 15 | 
| Percentage of Participants With Local Tolerability Symptoms at Day 22 | Local tolerability symptoms (burning/stinging) were assessed in participants at sites of study drug application. Symptoms were assessed on 4-point scale which ranges from 0 to 3, where 0 = none (no stinging/burning), 1 = mild (slight warm, tingling sensation); 2= moderate (definite warm; tingling/stinging sensation that is somewhat bothersome and severe); 3= severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores indicate high severity of symptoms. In this outcome, percentage of participants with each level of local tolerability (none, mild, moderate, severe) symptoms were reported. | Day 22 | 
| Percentage of Participants With Local Tolerability Symptoms at Day 29 | Local tolerability symptoms (burning/stinging) were assessed in participants at sites of study drug application. Symptoms were assessed on 4-point scale which ranges from 0 to 3, where 0 = none (no stinging/burning), 1 = mild (slight warm, tingling sensation); 2= moderate (definite warm; tingling/stinging sensation that is somewhat bothersome and severe); 3= severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores indicate high severity of symptoms. Percentage of participants with each level of local tolerability (none, mild, moderate, severe) symptoms were reported. | Day 29 | 
| Percentage of Participants With Local Tolerability Symptoms at Day 36 | Local tolerability symptoms (burning/stinging) were assessed in participants at sites of study drug application. Symptoms were assessed on 4-point scale which ranges from 0 to 3, where 0 = none (no stinging/burning), 1 = mild (slight warm, tingling sensation); 2= moderate (definite warm; tingling/stinging sensation that is somewhat bothersome and severe); 3= severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores indicate high severity of symptoms. Percentage of participants with each level of local tolerability (none, mild, moderate, severe) symptoms were reported. | Day 36 | 
| Percentage of Participants Who Achieved Success in Investigator's Static Global Assessment (ISGA) Score at Day 29 | ISGA assessed the severity of AD (except scalp) on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual hypo/hyper pigmentation, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Treatment success was defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2-grade improvement from baseline. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 29 | ISGA assessed the severity of AD (except scalp and venous access area) on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Percentage of participants with an ISGA score of 0 or 1 were reported. | Day 29 | 
| Time to Achieve Treatment Success Based on Investigator's Static Global Assessment (ISGA) | Time to achieve treatment success based on ISGA was defined as the time interval between the administrations of first dose of study drug until first documentation of success in ISGA. Success in ISGA was defined as an ISGA score of clear (0) or almost clear (1) with at least 2-grade improvement from baseline. It was analyzed using Kaplan-Meier method. | Baseline up to Day 29 | 
| Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Signs of AD included erythema, induration/papulation, exudation, excoriation and lichenification. Each sign was assessed on a 4- point scale ranges from 0 to 3, where 0= none, 1= mild, 2= moderate to 3= severe. Higher score indicates severe signs and symptoms of AD. | Baseline, Day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
atopic dermatitis