Clinical trial NCT03539601: A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD
Official title: A PHASE 3B/4, MULTICENTER, RANDOMIZED, ASSESSOR BLINDED, VEHICLE AND ACTIVE (TOPICAL CORTICOSTEROID AND CALCINEURIN INHIBITOR) CONTROLLED, PARALLEL GROUP STUDY OF THE EFFICACY, SAFETY, AND LOCAL TOLERABILITY OF CRISABOROLE OINTMENT, 2% IN PEDIATRIC AND ADULT SUBJECTS (AGES 2 YEARS AND OLDER) WITH MILD TO MODERATE ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis, Crisaborole ointment 2%, TCS, TCI
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-05-29
Enrollment: 237
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 4-week study will evaluate the safety and efficacy of crisaborole ointment 2%; crisaborole vehicle; topical corticosteroid and topical calcineurin inhibitor, applied twice daily (BID) in subjects who are at least 2 years of age with mild-moderate AD.

A Sub-Study of Optical Coherence Tomography and Biomarkers in Subjects ages 2 to \<18 years old, with Mild to Moderate Atopic Dermatitis, treated with Crisaborole Ointment, 2% or Crisaborole Vehicle Ointment or Hydrocortisone Butyrate 0.1% Cream applied BID will also be conducted at select sites.

Detailed description: Approximately 600 subjects will be enrolled in the study, of which at least 150 subjects aged 2-6; at least 140 subjects aged 7-11; at least 120 subjects aged 12-17 and up to 90 subjects will be adults. Subjects must have mild-moderate AD involving at least 5% treatable %BSA assessed on baseline/Day 1. Treatable %BSA will be defined as the percent of a subject's total body surface area that is AD involved, excluding the scalp.

Eligible subjects will be randomized at the Baseline/Day 1 visit. Randomization will be stratified by eligibility for TCS or TCI treatment as per national approved labels. Cohort 1 will be for subjects who are eligible for TCS therapy, and Cohort 2 will be for subjects who are not eligible for TCS therapy but eligible for TCI therapy. The investigational products will be applied BID for 28 days to the Treatable body surface area (BSA) identified at Baseline/Day 1.

The primary efficacy endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI) total score at Day 29.

For the efficacy comparison of crisaborole versus vehicle, subjects from both Cohort 1 and Cohort 2 are included in the analysis, adjusted for cohort effect. For the efficacy comparison of crisaborole versus TCS, only subjects from Cohort 1 are included in the analysis. For the comparison of crisaborole versus TCI, only subjects from Cohort 2 are included in the analysis.

Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment.

Scheduled study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8, Day 15, Day 22, Day 29 (End of treatment/Early termination), Day 43 or 14 Days after last dose if subject is terminated early from treatment. A follow up telephone call will be made by site staff to the subjects/subject's legally acceptable guardian(s) on Day 60 or at least 28 days after last dose if subject is terminated early from treatment. The Day 60 visit will be completed in the clinic for subjects enrolled in the OCT sub-study.

To further explore the benefit/risk of crisaborole ointment, 2%, a sub-study to evaluate differences in atrophic skin changes across study treatment groups in Cohort 1 will be conducted at select sites.

The sub-study will include obtaining Optical coherence tomography (OCT) imaging to evaluate atrophic changes in epidermal thickness during and after treatment with study investigational product in Cohort 1. This sub-study also provides an opportunity to explore differences in Transepidermal Water Loss (TEWL) and cutaneous inflammatory and barrier biomarkers associated with AD within the stratum corneum (SC) across treatment groups in Cohort 1. The Aquaflux (an evaporimeter) will be used in this sub-study to evaluate TEWL during and after treatment at select sub-study centers. Tape-strips will also be used in this sub-study to evaluate SC biomarkers from AD lesional and non-lesional skin.

This sub-study will include approximately 60 subjects from Cohort 1 that are enrolled in the main study (C3291037). Subjects will follow the main study assessments and visits as per the schedule of activities for the main study but will also follow additional procedures as described in the protocol. The telephone call at Day 60 in the main study is replaced with an in-clinic visit for sub-study participants.

Eligibility criteria: Inclusion Criteria:

Is male or female 2 years and older at the Screening visit/time of informed consent/assent diagnosed with mild-moderate AD (according to the criteria of Hanifin and Rajka), of at least 5% BSA.

Exclusion Criteria:

Has any clinically significant medical disorder, condition, or disease (including active or potentially recurrent non AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome.

Subjects in Cohort 1 are excluded if they have a contraindication for treatment with hydrocortisone butyrate cream 0.1%

Subjects in Cohort 2 are excluded if they have a contraindication for treatment with pimecrolimus cream, 1%

Primary outcomes:
measure: Percent Change From Baseline in the Eczema Area and Severity Index (EASI) Total Score at Day 29
timeFrame: Baseline, Day 29
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Discontinuations Due to AEs and SAEs
timeFrame: From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)
measure: Number of Participants With Local Tolerability Adverse Events (AEs)
timeFrame: From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Screening up to Day 29
measure: Number of Participants With Clinically Significant Abnormal Laboratory Parameters
timeFrame: Screening up to Day 29
Secondary outcomes:
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15 and 22
timeFrame: Baseline, Day 8, 15 and 22
measure: Number of Participants Who Achieved Success in the Investigator's Static Global Assessment (ISGA) (ISGA Score of Clear [0] or Almost Clear [1] With At-least a 2-Grade Improvement From Baseline) at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Number of Participants Who Achieved Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Number of Participants Who Achieved Greater Than or Equal to (>=) 75 Percent (%) Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Time to First Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score of Greater Than or Equal to (>=) 75%
timeFrame: Baseline up to Day 43
measure: Change From Baseline in Percent Body Surface Area (%BSA) at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
measure: Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
measure: Change From Baseline in Participant Reported Itch Severity Scale in Participants Aged 6-11 Years at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
measure: Change From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
measure: Time to Greater Than or Equal to (>=2) Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>) 12 Years
timeFrame: Baseline up to Day 29
measure: Time to >= 3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>)12 Years
timeFrame: Baseline up to Day 29
measure: Time >=2 Point to Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years
timeFrame: Baseline up to Day 29
measure: Time to >=3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years
timeFrame: Baseline up to Day 29
measure: Number of Participants Who Achieved >=2 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Number of Participants Who Achieved >=3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Number of Participants Who Achieved Greater Than or Equal to (>=) 2 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Number of Participants Who Achieved Greater Than or Equal to (>=) 3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29
timeFrame: Day 8, 15, 22 and 29
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) in Participants Greater Than or Equal to (>=) 16 Years at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
measure: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) in Participants Aged 4-15 Years at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
measure: Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) in Participants Aged 2-17 Years at Day 8, 15, 22 and 29
timeFrame: Baseline, Day 8, 15, 22 and 29
Other outcomes:
Locations:
city: Bryant
country: United States
facility: Dermatology Trial Associates
state: Arkansas
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Orange Park
country: United States
facility: Park Avenue Dermatology
state: Florida
city: Sweetwater
country: United States
facility: Lenus Research & Medical Group, LLC
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Louisville
country: United States
facility: DS Research
state: Kentucky
city: Raleigh
country: United States
facility: M3-Wake Research, Inc.
state: North Carolina
city: Arlington
country: United States
facility: Arlington Research Center, Inc.
state: Texas
city: Layton
country: United States
facility: Tanner Clinic
state: Utah
city: Norfolk
country: United States
facility: Virginia Clinical Research, Inc
state: Virginia
city: Munchen
country: Germany
facility: Klinikum der Universitat Munchen
state: Bayern
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim, Fachbereich Dermatologie und Allergologie, Dermatologische Ambulanz
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
state: NRW
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein, Campus Lubeck
state: Schleswig-holstein
city: Berlin
country: Germany
facility: ISA - Interdisciplinary Study Association GmbH
city: Frankfurt am Main
country: Germany
facility: Universitaetsklinikum Frankfurt
city: L'Aquila
country: Italy
facility: UOSD Dermatologia Gen. ed Oncologica DU, PO San Salvatore
state: AQ
city: Genova
country: Italy
facility: DiSSal Sezione di Dermatologia Az. Ospedaliera Universitaria
state: GE
city: Roma
country: Italy
facility: Ospedale San Pietro Fatebenefratelli
state: RM
city: Roma
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico Tor Vergata
state: Rome
city: Krakow
country: Poland
facility: Barbara Rewerska Diamond Clinic
state: Malopolska
city: Katowice
country: Poland
facility: Silmedic sp. z o.o
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne sp. z o.o.
city: Warszawa
country: Poland
facility: Klinika Ambroziak Sp. z O. O.
city: Warszawa
country: Poland
facility: ROYALDERM Agnieszka Nawrocka
city: Orebro
country: Sweden
facility: Barn och Ungdomskliniken
city: Orebro
country: Sweden
facility: Avdelningen for Kliniska Provningar
city: Bern
country: Switzerland
facility: Universitatsklinik fuer Dermatologie
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: Zurich
country: Switzerland
facility: Universitats-Kinderspital Zurich
city: Torpoint
country: United Kingdom
facility: Rame Medical Ltd, Penntorr Health
state: Cornwall
city: Dundee
country: United Kingdom
facility: NHS Tayside, Ninewells Hospital and Medical School
state: Scotland
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: