Clinical trial NCT03915496: Study Evaluating the Mechanism of Action of PF-04965842 Monotherapy for Moderate-to-severe Atopic Dermatitis
Official title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO INVESTIGATE THE MECHANISM OF ACTION OF ABROCITINIB MONOTHERAPY IN ADULT PARTICIPANTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: atopic dermatitis
atopic eczema
eczema
JAK
janus kinase
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Fold-Change From Baseline in Atopic Dermatitis Biomarkers in Lesional and Non-lesional Skin at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Fold-Change From Baseline in Cellular (T-cell and Dendritic Cell) Inflammation Markers at Week 12
timeFrame: Baseline, Week 12
measure: Fold-Change From Baseline in Epidermal Hyperplasia Markers in Skin Biopsies and Skin Thickness at Week 12
timeFrame: Baseline, Week 12
measure: Fold-Change From Baseline in Blood Biomarkers for Inflammation and Immune Response at Week 12
timeFrame: Baseline, Week 12
measure: Percent-Change From Baseline in T-cell Lymphocyte Subset Populations at Week 12
timeFrame: Baseline, Week 12
measure: 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
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response ≥ 75% Improvement From Baseline Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, and 12
measure: Percentage of Participants With >=4 Points at Baseline and Achieving >=4 Points Improvement From Baseline in Numeric Rating Scale for Severity of Pruritus (PP-NRS) at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants Achieving EASI Response ≥ 90% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline to Week 2, 4, 8 and 12
measure: Percentage of Participants Achieving EASI Response ≥ 50% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline to Week 2, 4, 8 and 12
measure: Percent Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline to 16 weeks
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Baseline to 16 weeks
measure: Number of Participants Who Discontinued From the Study Due to TEAEs
timeFrame: Baseline to 16 weeks
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline to 16 weeks
Other outcomes:
measure: Change From Baseline in Erythrocytes at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in Reticulocytes at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in Platelet Counts at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in Interleukin 6 at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in Erythropoietin at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in Thrombopoietin at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Change From Baseline in Night Time Itch Scale Score at Week 2, 4, 8 and 12
timeFrame: Baseline and Week 2, 4, 8 and 12
measure: Plasma PF-04965842 Concentration
timeFrame: Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
measure: Plasma PF-06471658 (M1) Concentration
timeFrame: Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
measure: Plasma PF-07055087 (M2) Concentration
timeFrame: Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
measure: Plasma PF-07054874 (M4) Concentration
timeFrame: Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
Locations:
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC - IDS Pharmacy
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Largo
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center, PC - Dermatology Research
state: Indiana
city: Dearborn
country: United States
facility: Wayne Health - Wayne State Dermatology
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Dallas
country: United States
facility: Menter Dermatology Research Institute
state: Texas
city: Calgary
country: Canada
facility: Beacon Dermatology
state: Alberta
city: Montreal
country: Canada
facility: Innovaderm Research, Inc.
state: Quebec
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: