Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis

NCT03233529 | Completed Phase 2 Results FDA Drug

• 1 other identifier: C3291001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to characterize the mechanism of action of crisaborole ointment 2%, by evaluation of efficacy and changes in key skin biomarkers in atopic dermatitis (AD) lesions treated with crisaborole ointment 2% over vehicle, in subjects with mild to moderate AD. Two identified AD skin lesions for each subject will be treated for the first 15 days, one with crisaborole ointment 2% and one with vehicle, in a blinded manner, and biopsies for biomarker analysis will be performed on the lesions. Following completion of the blinded treatment period, subjects will start the 28 day open label period during which all AD affected skin lesions will be treated with crisaborole ointment 2% twice daily.

Conditions

Dermatitis, Atopic

Keywords

atopic dermatitis; atopic eczema; eczema; topical treatment; skin diseases; phosphodiesterase-4 inhibitor; PDE-4 inhibitor; crisaborole

Outcome Measures

Primary Outcomes (8)

• Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

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

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

• Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

  Baseline (Day 1), Day 15

Secondary Outcomes (11)

• Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  Baseline (Day 1), Day 15

• Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  Baseline (Day 1), Day 15

• Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15

  Baseline (Day 1), Day 15

• Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15

  Day 15

• Number of Participants With Categorical Histological Response at Day 15

  Day 15

Study Arms (2)

Crisaborole ointment

EXPERIMENTAL

Drug: Crisaborole ointment 2% BID

Placebo ointment (vehicle)

PLACEBO COMPARATOR

Drug: Placebo ointment (vehicle)

Interventions

Crisaborole ointment 2% BID DRUG

Crisaborole ointment 2% BID for 15 days (double blind); additional 28 days (open label)

Crisaborole ointment

Placebo ointment (vehicle) DRUG

Placebo ointment (vehicle) BID for 15 days (double blind)

Placebo ointment (vehicle)

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of active atopic dermatitis (AD) with at least 6 month history prior to Screening and that has been clinically stable for 1 month.
• Investigator's Static Global Assessment (ISGA) of 2 (mild) or 3 (moderate) at Baseline.
• Body surface area (BSA) covered with AD of at least 0.5% and no more than 10% at Baseline, calculation excluding face, scalp, axilla, genitals, groin area, palms, back of the hands, and soles.
• Two lesions of AD at least 3 cm x 3 cm in size and at least 5 cm apart, with identical Lesion ISGA score of greater than/equal to 3.

You may not qualify if:

• Clinically infected AD or requires high potency topical corticosteroids or systemic (oral/injectable) corticosteroids to manage AD.
• History of angioedema or anaphylaxis to topical products or known sensitivity to components of crisaborole ointment 2%.
• History of cancer (except squamous or basal cell carcinoma or carcinoma in situ of the skin).
• Previous treatment with any topical or systemic PDE4 inhibitor unless stopped for the reason of lack of efficacy.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Innovaderm Research Incorporated

Montreal, Quebec, H2K 4L5, Canada

Location

Related Publications (1)

• Bissonnette R, Pavel AB, Diaz A, Werth JL, Zang C, Vranic I, Purohit VS, Zielinski MA, Vlahos B, Estrada YD, Saint-Cyr Proulx E, Ports WC, Guttman-Yassky E. Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial. J Allergy Clin Immunol. 2019 Nov;144(5):1274-1289. doi: 10.1016/j.jaci.2019.06.047. Epub 2019 Aug 13.

  PMID: 31419544 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Dermatitis, Atopic; Eczema; Skin Diseases

Interventions

BID protein, human

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; 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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 28, 2017
• Study Start: July 31, 2017
• Primary Completion: May 4, 2018
• Study Completion: May 4, 2018
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)