Study to Assess Efficacy and Safety of Two Regimens of Crisaborole Ointment 2% in Japanese Participants Aged ≥2 Years With Mild to Moderate Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT03954158
• Recruitment Status: Completed
• First Posted: May 17, 2019
• Results First Posted: July 14, 2020
• Last Update Posted: July 14, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 15, 2019
• First Posted Date: May 17, 2019
• Results First Submitted Date: May 27, 2020
• Results First Posted Date: July 14, 2020
• Last Update Posted Date: July 14, 2020
• Actual Study Start Date: June 15, 2019
• Actual Primary Completion Date: December 16, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 5, 2020)

Change From Baseline in Total Sign Score (TSS) in Target Lesions at Day 15: Crisaborole Ointment 2% Versus Vehicle [ Time Frame: Baseline, Day 15 ]

Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity.

Original Primary Outcome Measures (submitted: May 15, 2019)

Change from baseline in Total Sign Score (TSS) in target lesions treated with crisaborole ointment or vehicle on Day 15 in each regimen for each cohort [ Time Frame: Day15 ]

To compare the efficacy of crisaborole ointment 2%, administered QD or BID relative to the corresponding vehicle (QD or BID), on TSS assessment in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).

Current Secondary Outcome Measures (submitted: July 5, 2020)

• Change From Baseline in Total Sign Score in Target Lesions at Day 15: Crisaborole Ointment 2% BID Versus Crisaborole Ointment 2% QD [ Time Frame: Baseline, Day 15 ]
  Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity.
• Change From Baseline in Total Sign Score in Target Lesions at Day 8: Crisaborole Ointment 2% Versus Vehicle [ Time Frame: Baseline, Day 8 ]
  Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity.
• Change From Baseline in Investigator's Static Global Assessment (ISGA) Score in Target Lesions at Day 8 and Day 15 [ Time Frame: Baseline, Day 8, Day 15 ]
  ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicated 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).
• Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Target Lesions up to Day 15 in Participants Aged 12 Years or More [ Time Frame: Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ]
  The severity of itch (pruritus) due to AD at the target lesion was assessed using the peak pruritus NRS. Participants aged 12 years or more, were asked to rate their itch severity at the worst moment during the past 24 hours on a scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores represented more severe itch.
• Change From Baseline in Itch Severity Scale in Target Lesions up to Day 15 in Participants Aged Between 6 to 11 Years [ Time Frame: Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ]
  The itch severity scale was used for participants >=6 to 11 years of age to assess severity of itch (pruritus) due to AD at the target lesion. In this assessment, participants were asked to choose a unit that showed how itchy their skin had been on day of assessment on a 5-point scale ranging from 1= not itchy to 5= very itchy, where higher scores represented more severe itch.
• Change From Baseline in Observer Reported Itch Severity Numerical Rating Scale in Target Lesions up to Day 15 in Participants Aged Between 2 to 11 Years [ Time Frame: Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ]
  Observer reported itch severity NRS was used for participants >=2 and < 12 years of age to assess severity of itch (pruritus) due to AD at the target lesion. Parents/caregivers (of participants) were asked to rate participants' itch (i.e. scratching, rubbing) at the worst moment during past 24 hours on a scale of 0 (no itch) to 10 (worst itch imaginable); higher scores represented more severe itch.
• Number of Participants With Treatment-Emergent Adverse Events (AEs) in the Target Lesions Per Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term [ Time Frame: Day 1 up to 35 days after end of treatment (maximum up to Day 50) ]
  An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state. For this outcome measure, treatment-emergent AEs occurred at each treated target lesion were summarized. MedDRA version 22.1 coding dictionary was used.
• Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) by Treatment Regimen [ Time Frame: Day 1 up to 35 days after end of treatment (maximum up to Day 50) ]
  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 and up to end of study that were absent before treatment or that worsened relative to pre-treatment state.

Original Secondary Outcome Measures (submitted: May 15, 2019)

• Change from baseline in TSS in target lesions treated with crisaborole ointment or vehicle on Day 15 in each regimen for each cohort [ Time Frame: Day 15 ]
  To evaluate the efficacy of crisaborole ointment 2% BID relative to crisaborole ointment 2% QD, on TSS assessment in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
• Change from baseline in TSS in target lesions treated with crisaborole ointment or vehicle on Day 8 in each regimen for each cohort [ Time Frame: Day 8 ]
  To evaluate the efficacy of crisaborole ointment 2%, administered QD or BID, on TSS in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
• Change from baseline in investigator's static global assessment (ISGA) in target lesions treated with crisaborole ointment or vehicle on Day 8 and Day 15 in each regimen for each cohort [ Time Frame: Day 8, Day 15 ]
  To evaluate the efficacy of crisaborole ointment 2%, administered QD or BID, on ISGA in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
• Change from baseline in Pruritus assessments in target lesions treated with crisaborole ointment or vehicle at each day up to Day 15 in each regimen [ Time Frame: Up to Day 15 ]
  To evaluate the efficacy of crisaborole ointment 2%, administered QD or BID, on Pruritus assessments in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in each regimen for each cohort [ Time Frame: Up to Day 15 ]
  To assess the safety and local tolerability of crisaborole ointment 2%, administered QD or BID, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess Efficacy and Safety of Two Regimens of Crisaborole Ointment 2% in Japanese Participants Aged ≥2 Years With Mild to Moderate Atopic Dermatitis
• Official Title: A Phase 2b, Multi Center, Randomized, Double-Blind, Vehicle-Controlled, Intra-Participant Study, to Evaluate Efficacy and Safety of Two Regimens of Crisaborole Ointment 2% in Japanese Pediatric and Adult Participants (2 Years and Older) With Mild to Moderate Atopic Dermatitis
• Brief Summary: This is a Phase 2b, multi-center, randomized, double-blind, vehicle-controlled, intraparticipant study to evaluate efficacy and safety of two regimens of crisaborole ointment 2% in Japanese pediatric and adult participants (cohort 1: 12 years and older, cohort 2: 2 to under 12 years old) with mild to moderate Atopic Dermatitis (AD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Crisaborole ointment 2%
  BID regimen
• Drug: Vehicle
  BID regimen
• Drug: Crisaborole ointment 2%
  QD regimen
• Drug: Vehicle
  QD regimen

Study Arms

• Experimental: Crisaborole ointment 2% once daily (QD) vs vehicle QD
  intra-participant comparison, treatment will be randomly assigned to target lesion 1 and lesion 2.
  Interventions:

  • Drug: Crisaborole ointment 2%
  • Drug: Vehicle
• Experimental: Crisaborole ointment 2% twice daily (BID) vs vehicle BID
  Intra-participant comparison, treatment will be randomly assigned to target lesion 1 and lesion 2.
  Interventions:

  • Drug: Crisaborole ointment 2%
  • Drug: Vehicle

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 2, 2019): 81
• Original Estimated Enrollment (submitted: May 15, 2019): 80
• Actual Study Completion Date: December 16, 2019
• Actual Primary Completion Date: December 16, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female participants ages; Cohort 1: 12 years and older at the time of consent. Cohort 2: 2 years to under 12 years old at the time of consent.
• Has confrimed clinical diagnosis of active AD according to Hanifin and Rajka criteria and has at least 6 months history prior to screening and has been clinically stable for more than 1 month
• Has at least 1% and no more than 30% BSA at baseline/Day1, excluding scalp, genitals and groin area
• Has a Investigator's static global assessment (ISGA) score of Mild (2) or Moderate (3) on Day 1.

Exclusion Criteria:

• Has other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Participants had previous treatment with any topical or systemic PDE-4 inhibitor.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03954158
• Other Study ID Numbers: C3291028
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2020