Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to Joel Schlessinger  1 , Julie S Shepard  2 , Richard Gower  3 , John C Su  4   5 , Charles Lynde  6 , Amy Cha  7 , William C Ports  8 , Vivek Purohit  8 , Liza Takiya  9 , John L Werth  10 , Chuanbo Zang  11 , Bonnie Vlahos  12 ; CARE 1 Investigators Affiliations Expand Affiliations 1 Advanced Skin Research Center, Skin Specialists PC, 2802 Oak View Dr, Omaha, NE, 68144, USA. skindoc@lovelyskin.com. 2 Ohio Pediatric Research Association, Dayton, OH, USA. 3 Marycliff Clinical Research, Spokane, WA, USA. 4 Department of Paediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia. 5 Department of Dermatology, Monash University, Eastern Health, Melbourne, VIC, Australia. 6 Department of Medicine, Lynde Institute for Dermatology, Markham, ON, Canada. 7 Pfizer Inc, New York, NY, USA. 8 Global Product Development, Pfizer Inc, Groton, CT, USA. 9 Medical Affairs, Pfizer Inc, Collegeville, PA, USA. 10 Clinical Development and Operations, Pfizer Inc, Collegeville, PA, USA. 11 Biostatistics, Pfizer Inc, Collegeville, PA, USA. 12 Global Clinical Development, Pfizer Inc, Collegeville, PA, USA. PMID: 32212104 PMCID: PMC7125059 DOI: 10.1007/s40257-020-00510-6 Free PMC article Item in Clipboard

Joel Schlessinger, Julie S Shepard, Richard Gower, John C Su, Charles Lynde, Amy Cha, William C Ports, Vivek Purohit, Liza Takiya, John L Werth, Chuanbo Zang, Bonnie Vlahos, CARE 1 Investigators, Joel Schlessinger, Julie S Shepard, Richard Gower, John C Su, Charles Lynde, Amy Cha, William C Ports, Vivek Purohit, Liza Takiya, John L Werth, Chuanbo Zang, Bonnie Vlahos, CARE 1 Investigators

Abstract

Background: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).

Objectives: The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study.

Methods: Infants (3 to < 24 months) with Investigator's Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory).

Results: Included were 137 infants total (mean age [SD], 13.6 months [6.42]), with 21 in the PK cohort (12.7 months [6.58]). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was - 57.5%, and mean change in Patient-Oriented Eczema Measure total score was - 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years.

Conclusions: In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mild-to-moderate AD with systemic exposures similar to patients aged ≥ 2 years.

Clinical trial registration: NCT03356977.

Conflict of interest statement

J. Schlessinger has no conflicts of interest to declare. J. S. Shepard was compensated as a principal investigator for this study and was also compensated to serve on an advisory board for Pfizer Inc. R. Gower has received research grants for Pfizer crisaborole clinical trials, and consulting fees for participating in the Pfizer Crisaborole Advisory Board. J. C. Su has been an investigator, speaker, and/or advisor for Pfizer Inc., Amgen, AbbVie, Ego Pharmaceuticals, Eli Lilly, GlaxoSmithKline, Janssen/Johnson & Johnson, L’Oréal, Meda, Novartis, Pierre Fabre, and Sanofi. C. Lynde has served as a principal investigator, consultant, and/or speaker for Pfizer Inc., AbbVie, Bausch, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, and Valeant. A. Cha, V. Purohit, L. Takiya, J. L. Werth, C. Zang, and B. Vlahos are employees and stockholders of Pfizer Inc. W. C. Ports was an employee of Pfizer Inc. at the time of this study and is a stockholder of Pfizer Inc.

Figures

Fig. 1
Fig. 1
ISGA response with crisaborole. 95% CIs were obtained by Clopper–Pearson exact method. ISGA success was defined as ISGA clear (0) or almost clear (1) with ≥ 2-grade improvement from baseline. ISGA Investigator’s Static Global Assessment
Fig. 2
Fig. 2
Mean percentage change from baseline in EASI score with crisaborole. EASI Eczema Area and Severity Index, SE standard error
Fig. 3
Fig. 3
Mean change from baseline in POEM total score with crisaborole. POEM Patient-Oriented Eczema Measure, SE standard error
Fig. 4
Fig. 4
Mean change from baseline in POEM subscale scores with crisaborole. BL baseline, POEM Patient-Oriented Eczema Measure, SE standard error

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