Dermatitis, Atopic
Conditions
Keywords
atopic dermatitis
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.
Interventions
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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 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. |
| 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 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. |
| 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 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29 | Baseline (Day 1), Day 29 | The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 2-15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the children's life; 2-6 = small effect on the children's life; 7-12 = moderate effect on the children's life; 13-18 = very large effect on the children's life; 19-30 = extremely large effect on the children's life. Higher scores indicate more impact on quality of life of children. |
| Time to Improvement in Pruritus | Baseline (Day 1) up to Day 29 | Time to improvement in pruritus was defined as the time interval between the administration of first dose of study drug till the first documentation of improvement in pruritus. Improvement in pruritus was defined as achieving none (0) or mild (1) score with at least a 1- grade improvement from baseline. Severity of pruritus was assessed on 4-point numeric scale ranges from 0 to 3, where 0= none (no itching), 1= mild (occasional, slight itching/scratching), 2= moderate (constant or intermittent itching/scratching which is not disturbing sleep) and 3= severe (bothersome itching/scratching which is disturbing sleep). Higher scores indicated more severe condition. It was analyzed using Kaplan-Meier method. |
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 | Baseline (Day 1), Day 29 | The DLQI was a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants. |
| Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score at Day 29 | Baseline (Day 1), Day 29 | The DFI was a 10-item disease questionnaire that measures the impact of having a child with AD on family quality of life. It was completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question was scored on a 4-point scale ranging from 0 (good) to 3 (worst), where higher scores indicated worst quality of life of family. The DFI total score was the sum of individual scores of the 10 questions and ranges from 0 (good) to 30 (worst), where higher DFI scores indicated worst quality of life of family. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AN2728 Ointment, 2 Percent (%) AN2728 ointment, 2% was applied topically twice daily, to all treatable AD-involved areas (excluding scalp), from Day 1 up to Day 28 in each participant. Treatable AD-involved areas were identified at Baseline (Day 1) by investigator. | 513 |
| AN2728 Ointment, Vehicle AN2728 ointment, vehicle was applied topically twice daily, to all treatable AD-involved areas (excluding scalp), from Day 1 up to Day 28 in each participant. Treatable AD-involved areas were identified at Baseline (Day 1) by investigator. | 250 |
| Total | 763 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Other | 1 | 6 |
| Overall Study | Randomised but not treated | 1 | 0 |
| Overall Study | Withdrawal by parent/guardian | 14 | 20 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | AN2728 Ointment, 2 Percent (%) | AN2728 Ointment, Vehicle | Total |
|---|---|---|---|
| Age, Customized 12 -17 years | 126 Participants | 57 Participants | 183 Participants |
| Age, Customized >=18 years | 77 Participants | 29 Participants | 106 Participants |
| Age, Customized 2 -11 years | 310 Participants | 164 Participants | 474 Participants |
| Gender Female | 282 Participants | 138 Participants | 420 Participants |
| Gender Male | 231 Participants | 112 Participants | 343 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 92 / 510 | 54 / 247 |
| serious Total, serious adverse events | 3 / 510 | 0 / 247 |
Outcome results
Primary
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.
Time frame: Baseline, Day 8
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings at Day 8 | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings at Day 8 | 0 participants |
Primary
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.
Time frame: Baseline (Day 1), Day 36
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Day 36 | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Day 36 | 0 participants |
Primary
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.
Time frame: Baseline up to Day 36
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Number of Participants With Clinically Significant Laboratory Values | 4 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Clinically Significant Laboratory Values | 4 participants |
Primary
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.
Time frame: AEs: Baseline (Day 1) up to Day 29, SAEs: Baseline (Day 1) up to Day 36
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | SAEs | 3 participants |
| AN2728 Ointment, 2 Percent (%) | Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | AEs | 150 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | AEs | 79 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
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.
Time frame: Day 29
Population: ITT population included all participants who were randomized and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants Who Achieved Success in Investigator's Static Global Assessment (ISGA) Score at Day 29 | 31.4 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Investigator's Static Global Assessment (ISGA) Score at Day 29 | 18.0 percentage of participants |
p-value: <0.001Regression, Logistic
Primary
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.
Time frame: Baseline (Day 1)
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment. Here, number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Baseline | Moderate | 19.6 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Baseline | Mild | 23.8 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Baseline | Severe | 7.9 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Baseline | None | 48.7 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Baseline | Severe | 5.3 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Baseline | Mild | 21.9 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Baseline | Moderate | 16.6 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Baseline | None | 56.3 percentage of participants |
Primary
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.
Time frame: Day 15
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment. Here, N signifies those participants who were analyzed in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 15 | None | 68.0 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 15 | Mild | 20.9 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 15 | Moderate | 7.4 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 15 | Severe | 3.7 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 15 | Severe | 4.2 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 15 | None | 70.7 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 15 | Moderate | 9.6 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 15 | Mild | 15.5 percentage of participants |
Primary
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.
Time frame: Day 22
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment. Here, number of participants analyzed N signifies those participants who were analyzed in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 22 | None | 69.0 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 22 | Mild | 21.8 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 22 | Moderate | 6.8 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 22 | Severe | 2.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 22 | Severe | 3.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 22 | None | 71.4 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 22 | Moderate | 8.4 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 22 | Mild | 16.7 percentage of participants |
Primary
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.
Time frame: Day 29
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 29 | Moderate | 10.1 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 29 | None | 70.4 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 29 | Severe | 2.3 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 29 | Mild | 17.3 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 29 | Severe | 1.8 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 29 | Mild | 13.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 29 | None | 73.9 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 29 | Moderate | 10.8 percentage of participants |
Primary
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.
Time frame: Day 36
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 36 | None | 71.1 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 36 | Mild | 14.3 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 36 | Moderate | 9.1 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 36 | Severe | 5.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 36 | Severe | 2.3 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 36 | None | 77.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 36 | Moderate | 10.3 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 36 | Mild | 9.9 percentage of participants |
Primary
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.
Time frame: Day 8
Population: Safety population included all randomized participants who had at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 8 | None | 63.8 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 8 | Mild | 24.0 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 8 | Moderate | 9.1 percentage of participants |
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With Local Tolerability Symptoms at Day 8 | Severe | 3.1 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 8 | Severe | 0.8 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 8 | None | 73.0 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 8 | Moderate | 11.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With Local Tolerability Symptoms at Day 8 | Mild | 14.8 percentage of participants |
Secondary
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.
Time frame: Baseline, Day 29
Population: ITT population included all participants who were randomized and received study drug. Here, 'n' signifies those participants who were evaluable at specific time point for each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Erythema: Change at Day 29 (n =486, 224) | -0.7 units on a scale | Standard Deviation 0.79 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Exudation: Baseline (n =513, 250) | 0.7 units on a scale | Standard Deviation 0.78 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Exudation: Change at Day 29 (n =486, 224) | -0.4 units on a scale | Standard Deviation 0.8 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Erythema: Baseline (n =513, 250) | 1.7 units on a scale | Standard Deviation 0.59 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Excoriation: Change at Day 29 (n =486, 224) | -0.7 units on a scale | Standard Deviation 0.89 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Induration: Baseline (n =513, 250) | 1.8 units on a scale | Standard Deviation 0.61 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Lichenification: Baseline (n =513, 250) | 1.5 units on a scale | Standard Deviation 0.68 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Excoriation: Baseline (n =513, 250) | 1.5 units on a scale | Standard Deviation 0.72 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Lichenification: Change at Day 29 (n =486, 224) | -0.6 units on a scale | Standard Deviation 0.8 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Induration: Change at Day 29 (n =486, 224) | -0.7 units on a scale | Standard Deviation 0.83 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Lichenification: Change at Day 29 (n =486, 224) | -0.3 units on a scale | Standard Deviation 0.76 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Excoriation: Baseline (n =513, 250) | 1.5 units on a scale | Standard Deviation 0.68 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Erythema: Baseline (n =513, 250) | 1.6 units on a scale | Standard Deviation 0.59 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Erythema: Change at Day 29 (n =486, 224) | -0.3 units on a scale | Standard Deviation 0.81 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Induration: Baseline (n =513, 250) | 1.8 units on a scale | Standard Deviation 0.56 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Induration: Change at Day 29 (n =486, 224) | -0.4 units on a scale | Standard Deviation 0.76 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Exudation: Change at Day 29 (n =486, 224) | -0.1 units on a scale | Standard Deviation 0.84 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Excoriation: Change at Day 29 (n =486, 224) | -0.5 units on a scale | Standard Deviation 0.93 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Lichenification: Baseline (n =513, 250) | 1.5 units on a scale | Standard Deviation 0.76 |
| AN2728 Ointment, Vehicle | Change From Baseline in Signs of Atopic Dermatitis at Day 29 | Exudation: Baseline (n =513, 250) | 0.6 units on a scale | Standard Deviation 0.81 |
Secondary
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.
Time frame: Day 29
Population: ITT population included all participants who were randomized and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 29 | 48.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 29 | 29.7 percentage of participants |
Secondary
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.
Time frame: Baseline up to Day 29
Population: ITT population included all participants who were randomized and received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Time to Achieve Treatment Success Based on Investigator's Static Global Assessment (ISGA) | NA days |
| AN2728 Ointment, Vehicle | Time to Achieve Treatment Success Based on Investigator's Static Global Assessment (ISGA) | NA days |
Other Pre-specified
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29
The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 2-15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the children's life; 2-6 = small effect on the children's life; 7-12 = moderate effect on the children's life; 13-18 = very large effect on the children's life; 19-30 = extremely large effect on the children's life. Higher scores indicate more impact on quality of life of children.
Time frame: Baseline (Day 1), Day 29
Population: ITT population included all participants who were randomized and received study drug. Here, Number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29 | Baseline (n =404, 204) | 9.0 units on a scale | Standard Deviation 5.77 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29 | Change at Day 29 (n =376,180) | -4.0 units on a scale | Standard Deviation 4.92 |
| AN2728 Ointment, Vehicle | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29 | Baseline (n =404, 204) | 8.9 units on a scale | Standard Deviation 5.48 |
| AN2728 Ointment, Vehicle | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29 | Change at Day 29 (n =376,180) | -2.9 units on a scale | Standard Deviation 5.01 |
Other Pre-specified
Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score at Day 29
The DFI was a 10-item disease questionnaire that measures the impact of having a child with AD on family quality of life. It was completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question was scored on a 4-point scale ranging from 0 (good) to 3 (worst), where higher scores indicated worst quality of life of family. The DFI total score was the sum of individual scores of the 10 questions and ranges from 0 (good) to 30 (worst), where higher DFI scores indicated worst quality of life of family.
Time frame: Baseline (Day 1), Day 29
Population: ITT population included all participants who were randomized and received study drug. Here, ''N'' signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score at Day 29 | Baseline (n =431, 217) | 7.7 units on a scale | Standard Deviation 6.57 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score at Day 29 | Change at Day 29 (n =404, 190) | -3.6 units on a scale | Standard Deviation 5.18 |
| AN2728 Ointment, Vehicle | Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score at Day 29 | Baseline (n =431, 217) | 8.0 units on a scale | Standard Deviation 5.65 |
| AN2728 Ointment, Vehicle | Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score at Day 29 | Change at Day 29 (n =404, 190) | -2.8 units on a scale | Standard Deviation 4.75 |
Other Pre-specified
Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29
The DLQI was a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.
Time frame: Baseline (Day 1), Day 29
Population: ITT population included all participants who were randomized and received study drug. Here, ''N'' signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 | Baseline (n =97, 40) | 9.7 units on a scale | Standard Deviation 6.24 |
| AN2728 Ointment, 2 Percent (%) | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 | Change at Day 29 (n =93, 38) | -5.0 units on a scale | Standard Deviation 5.49 |
| AN2728 Ointment, Vehicle | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 | Baseline (n =97, 40) | 9.1 units on a scale | Standard Deviation 6.67 |
| AN2728 Ointment, Vehicle | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 | Change at Day 29 (n =93, 38) | -3.4 units on a scale | Standard Deviation 4.75 |
Other Pre-specified
Time to Improvement in Pruritus
Time to improvement in pruritus was defined as the time interval between the administration of first dose of study drug till the first documentation of improvement in pruritus. Improvement in pruritus was defined as achieving none (0) or mild (1) score with at least a 1- grade improvement from baseline. Severity of pruritus was assessed on 4-point numeric scale ranges from 0 to 3, where 0= none (no itching), 1= mild (occasional, slight itching/scratching), 2= moderate (constant or intermittent itching/scratching which is not disturbing sleep) and 3= severe (bothersome itching/scratching which is disturbing sleep). Higher scores indicated more severe condition. It was analyzed using Kaplan-Meier method.
Time frame: Baseline (Day 1) up to Day 29
Population: ITT population included all participants who were randomized and received study drug. Here, N'' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AN2728 Ointment, 2 Percent (%) | Time to Improvement in Pruritus | 1.41 days |
| AN2728 Ointment, Vehicle | Time to Improvement in Pruritus | 1.54 days |