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

Phase 3

Completed

Conditions: Dermatitis, Atopic

Interventions: Drug: AN2728 Topical Ointment, 2%
Drug: Matching vehicle control

Registration Number: NCT02118792

Lead Sponsor: Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 764

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AN2728 Topical Ointment, 2%	AN2728 Topical Ointment, 2%	AN2728 Topical Ointment, 2%, applied twice daily for up to 28 days
Matching vehicle control	Matching vehicle control	Matching vehicle control, applied twice daily for up to 28 days

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)	AEs: Baseline (Day 1) up to Day 29, SAEs: Baseline (Day 1) up to Day 36	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.
Percentage of Participants With Local Tolerability Symptoms at Day 36	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.
Number of Participants With Clinically Significant Laboratory Values	Baseline up to Day 36	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.
Percentage of Participants With Local Tolerability Symptoms at Day 29	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.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Day 36	Baseline (Day 1), 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.
Percentage of Participants With Local Tolerability Symptoms at Day 8	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.
Percentage of Participants With Local Tolerability Symptoms at Day 22	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.
Percentage of Participants Who Achieved Success in Investigator's Static Global Assessment (ISGA) Score at Day 29	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.
Percentage of Participants With Local Tolerability Symptoms at Baseline	Baseline (Day 1)	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.
Percentage of Participants With Local Tolerability Symptoms at Day 15	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.
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings at Day 8	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Time to Achieve Treatment Success Based on Investigator's Static Global Assessment (ISGA)	Baseline up to Day 29	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.
Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 29	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.
Change From Baseline in Signs of Atopic Dermatitis at Day 29	Baseline, 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.