Study Evaluating the Mechanism of Action of PF-04965842 Monotherapy for Moderate-to-severe Atopic Dermatitis

NCT03915496 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: B7451037JADE MOA
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 11

Brief Summary

B7451037 is a randomized, double-blind, placebo-controlled, parallel-group, Phase 2a study to investigate the mechanism of action of PF-04965842 by correlating efficacy outcomes with changes from baseline in key skin and blood biomarkers in adult participants at least 18 years of age with moderate-to-severe atopic dermatitis. Participants will be screened within 28 days prior to the first dose of study intervention to confirm eligibility. A total of approximately 51 participants will be randomized in a 1:1:1 ratio to receive PF-04965842 200 mg once daily (QD), PF004965842 100 mg QD, or matching placebo QD for 12 weeks. At the end of the 12-week study treatment, qualified participants will have the option to enter the long-term extension study B7451015 (NCT03422822). Participants discontinuing early from this study will undergo a 4-week off-treatment follow-up period.

Conditions

Atopic Dermatitis

Keywords

atopic dermatitis; atopic eczema; eczema; JAK; janus kinase

Outcome Measures

Primary Outcomes (1)

• Fold-Change From Baseline in Atopic Dermatitis Biomarkers in Lesional and Non-lesional Skin at Week 12

  Mean fold-changes from baseline at Week 12 in the biomarkers for general inflammation (Matrix Metallopeptidase \[MMP\]12), hyperplasia (Keratin \[KRT\]16), Th2 immune response (C-C motif chemokine ligand \[CCL\]17, CCL18, CCL26), and Th22 immune response (S100 calcium binding protein A \[S100A\]8, S100A9, S100A12), in lesional (LS) and non-lesional (NL) skin tissues, respectively. Expression levels from RT-PCR are normalized to the housekeeping gene RPLP0 by negatively transforming the Ct values to -dCt.

  Baseline, Week 12

Secondary Outcomes (15)

• Fold-Change From Baseline in Cellular (T-cell and Dendritic Cell) Inflammation Markers at Week 12

  Baseline, Week 12

• Fold-Change From Baseline in Epidermal Hyperplasia Markers in Skin Biopsies and Skin Thickness at Week 12

  Baseline, Week 12

• Fold-Change From Baseline in Blood Biomarkers for Inflammation and Immune Response at Week 12

  Baseline, Week 12

• Percent-Change From Baseline in T-cell Lymphocyte Subset Populations at Week 12

  Baseline, Week 12

• Response Based on at Least 4 Points Improvement in the Severity of Peak Pruritus Numerical Rating Scale (NRS) From Baseline and Changes From Baseline in Immunohistochemistry (IHC) and Gene Expression Biomarkers in Lesional Skin

  Baseline, Week 12

Other Outcomes (12)

• Change From Baseline in Erythrocytes at Week 2, 4, 8 and 12

  Baseline and Week 2, 4, 8 and 12

• Change From Baseline in Reticulocytes at Week 2, 4, 8 and 12

  Baseline and Week 2, 4, 8 and 12

• Change From Baseline in Platelet Counts at Week 2, 4, 8 and 12

  Baseline and Week 2, 4, 8 and 12

Study Arms (3)

PF-04965842 200 mg

EXPERIMENTAL

Drug: PF-04965842 200 mg

PF-04965842 100 mg

EXPERIMENTAL

Drug: PF-04965842 100 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PF-04965842 200 mg DRUG

PF-04965842 200 mg administered as two tablets to be taken orally once daily for 12 weeks

PF-04965842 200 mg

PF-04965842 100 mg DRUG

PF-04965842 100 mg administered as two tablets to be taken orally once daily for 12 weeks

PF-04965842 100 mg

Placebo DRUG

Placebo administered as two tablets to be taken orally once daily for 12 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of chronic moderate-to-severe atopic dermatitis (AD) for at least 1 year
• Recent history of inadequate response to medicated topical therapy for AD or required systemic therapy to control disease
• Moderate-to-severe AD defined as affected BSA at least 10%, IGA at least 3, EASI at least 16, Peak Pruritus NRS at least 4

You may not qualify if:

• A current or past medical history of conditions associated with thrombocytopenia, coagulopathy, or platelet dysfunction
• Currently have active forms of other inflammatory skin diseases, i.e. not AD, or have evidence of skin conditions (e.g. psoriasis, seborrheic dermatitis, lupus) at the time of Day 1 that would interfere with evaluation of AD or response to treatment
• Participants who have received prior treatment with any systemic JAK inhibitors
• Require treatment with prohibited concomitant medication(s) or have received a prohibited concomitant medication within specified time frames prior to the first dose of study medication, including topical treatments that could affect AD
• Pregnant or breastfeeding women or sexually-active women of childbearing potential who are unwilling to use contraception

Sponsors & Collaborators

• Pfizer: lead

Study Sites (11)

California Dermatology & Clinical Research Institute

Encinitas, California, 92024, United States

Location

Keck School of Medicine of USC - IDS Pharmacy

Los Angeles, California, 90033, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Olympian Clinical Research

Largo, Florida, 33770, United States

Location

ForCare Clinical Research

Tampa, Florida, 33613, United States

Location

The Indiana Clinical Trials Center, PC - Dermatology Research

Plainfield, Indiana, 46168, United States

Location

Wayne Health - Wayne State Dermatology

Dearborn, Michigan, 48124, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Menter Dermatology Research Institute

Dallas, Texas, 75246, United States

Location

Beacon Dermatology

Calgary, Alberta, T3E 0B2, Canada

Location

Innovaderm Research, Inc.

Montreal, Quebec, H2X 2V1, Canada

Location

Related Links

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

MeSH Terms

Conditions

Dermatitis, Atopic; Eczema

Interventions

abrocitinib

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 2
• 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: March 22, 2019
• First Posted: April 16, 2019
• Study Start: June 18, 2020
• Primary Completion: November 16, 2021
• Study Completion: November 16, 2021
• Last Updated: February 8, 2023
• Results First Posted: February 8, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); US (9)