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

NCT02118792 | Completed Phase 3 Results

• 1 other identifier: AN2728-AD-302
• Study Type: interventional
• Target: 764
• Locations: 1 country
• Sites: 1

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.

Conditions

Dermatitis, Atopic

Keywords

atopic dermatitis

Outcome Measures

Primary Outcomes (11)

• 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

• 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

Secondary Outcomes (3)

• Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 29

  Day 29

• Time to Achieve Treatment Success Based on Investigator's Static Global Assessment (ISGA)

  Baseline up to Day 29

• Change From Baseline in Signs of Atopic Dermatitis at Day 29

  Baseline, Day 29

Other Outcomes (4)

• Time to Improvement in Pruritus

  Baseline (Day 1) up to Day 29

• Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Day 29

  Baseline (Day 1), Day 29

• Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29

  Baseline (Day 1), Day 29

Study Arms (2)

AN2728 Topical Ointment, 2%

EXPERIMENTAL

AN2728 Topical Ointment, 2%, applied twice daily for up to 28 days

Drug: AN2728 Topical Ointment, 2%

Matching vehicle control

PLACEBO COMPARATOR

Matching vehicle control, applied twice daily for up to 28 days

Drug: Matching vehicle control

Interventions

AN2728 Topical Ointment, 2% DRUG

AN2728 Topical Ointment, 2%

Matching vehicle control DRUG

Matching vehicle control

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Anacor Investigational Site

Henrico, Virginia, United States

Location

Related Publications (8)

• Stein Gold LF, Tom WL, Shi V, Sanders P, Zang C, Vlahos B, Cha A. Impact of Crisaborole in Treatment-Experienced Patients With Mild-to-Moderate Atopic Dermatitis. Dermatitis. 2024 Jan-Feb;35(1):84-91. doi: 10.1089/derm.2023.0112. Epub 2024 Jan 11.

  PMID: 38206678 DERIVED

• Luger TA, Hebert AA, Zaenglein AL, Silverberg JI, Tan H, Ports WC, Zielinski MA. Subgroup Analysis of Crisaborole for Mild-to-Moderate Atopic Dermatitis in Children Aged 2 to < 18 Years. Paediatr Drugs. 2022 Mar;24(2):175-183. doi: 10.1007/s40272-021-00490-y. Epub 2022 Mar 16.

  PMID: 35292919 DERIVED

• Geng B, Hebert AA, Takiya L, Miller L, Werth JL, Zang C, Sanders P, Lebwohl MG. Efficacy and Safety Trends with Continuous, Long-Term Crisaborole Use in Patients Aged >/= 2 Years with Mild-to-Moderate Atopic Dermatitis. Dermatol Ther (Heidelb). 2021 Oct;11(5):1667-1678. doi: 10.1007/s13555-021-00584-y. Epub 2021 Aug 11.

  PMID: 34379285 DERIVED

• Thyssen JP, Zang C, Neary MP, Bushmakin AG, Cappelleri JC, Cha A, Russo C, Luger TA. Translating the Investigator's Static Global Assessment to the Eczema Area and Severity Index in Studies of Crisaborole for Atopic Dermatitis. Dermatol Ther (Heidelb). 2021 Jun;11(3):845-853. doi: 10.1007/s13555-021-00509-9. Epub 2021 Mar 13.

  PMID: 33728583 DERIVED

• Stein Gold LF, Takiya L, Zang C, Sanders P, Feldman SR. Demographics and Baseline Disease Characteristics of Early Responders to Crisaborole for Atopic Dermatitis. J Drugs Dermatol. 2020 Jun 1;19(6):619-624.

  PMID: 32574023 DERIVED

• Silverberg JI, Tallman AM, Ports WC, Gerber RA, Tan H, Zielinski MA. Evaluating the Efficacy of Crisaborole Using the Atopic Dermatitis Severity Index and Percentage of Affected Body Surface Area. Acta Derm Venereol. 2020 Jun 11;100(13):adv00170. doi: 10.2340/00015555-3489.

  PMID: 32318744 DERIVED

• Simpson EL, Paller AS, Boguniewicz M, Eichenfield LF, Feldman SR, Silverberg JI, Chamlin SL, Zane LT. Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families. Dermatol Ther (Heidelb). 2018 Dec;8(4):605-619. doi: 10.1007/s13555-018-0263-0. Epub 2018 Oct 22.

  PMID: 30345457 DERIVED

• Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, Eichenfield LF, Forsha DW, Rees WC, Simpson EL, Spellman MC, Stein Gold LF, Zaenglein AL, Hughes MH, Zane LT, Hebert AA. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016 Sep;75(3):494-503.e6. doi: 10.1016/j.jaad.2016.05.046. Epub 2016 Jul 11.

  PMID: 27417017 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 21, 2014
• Study Start: March 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: March 6, 2017
• Results First Posted: March 6, 2017

Record last verified: 2017-01

Locations

US (1)