Phase 2
Completed N=46
Study Evaluating the Mechanism of Action of PF-04965842 Monotherapy for Moderate-to-severe Atopic Dermatitis
Source: ClinicalTrials.gov NCT03915496 ↗Enrolled (actual)
46
Serious AEs
2.2%
Results posted
Feb 2023
Primary outcomePrimary: Fold-Change From Baseline in Atopic Dermatitis Biomarkers in Lesional and Non-lesional Skin at Week 12 — -5.896; -15.604; -0.729; -0.506 Fold change
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Fold-Change From Baseline in Atopic Dermatitis Biomarkers in Lesional and Non-lesional Skin at Week 12 |
-5.896; -15.604; -0.729; -0.506; -3.150; -3.354 | — |
| SECONDARY Fold-Change From Baseline in Cellular (T-cell and Dendritic Cell) Inflammation Markers at Week 12 |
-1.622; -2.460; -1.326; -1.952; -2.371; -1.054 | — |
| SECONDARY Fold-Change From Baseline in Epidermal Hyperplasia Markers in Skin Biopsies and Skin Thickness at Week 12 |
-1.638; -1.911; -1.153; -1.310; -1.508; -1.185 | — |
| SECONDARY Fold-Change From Baseline in Blood Biomarkers for Inflammation and Immune Response at Week 12 |
-0.247; -0.519; -0.245; -0.619; -0.880; 0.108 | — |
| SECONDARY Percent-Change From Baseline in T-cell Lymphocyte Subset Populations at Week 12 |
-0.2; 3.6; 1.7; -14.5; 14.2; 1.5 | — |
| SECONDARY 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 |
0.242; 0.484; 0.439; 0.474; 0.464; 0.238 | — |
| SECONDARY 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 |
0; 7.7; 0; 26.7; 35.7; 0 | — |
| SECONDARY Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response ≥ 75% Improvement From Baseline Week 2, 4, 8 and 12 |
6.3; 38.5; 0; 46.7; 50.0; 0 | — |
| SECONDARY 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 |
25.0; 57.1; 6.3; 53.3; 64.3; 0 | — |
| SECONDARY Percentage of Participants Achieving EASI Response ≥ 90% Improvement From Baseline at Week 2, 4, 8 and 12 |
0; 0; 0; 20.0; 28.6; 0 | — |
| SECONDARY Percentage of Participants Achieving EASI Response ≥ 50% Improvement From Baseline at Week 2, 4, 8 and 12 |
37.5; 61.5; 12.5; 66.7; 100.0; 6.7 | — |
| SECONDARY Percent Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8 and 12 |
-9.6; -17.3; 4.0; -18.7; -23.8; 2.1 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
10; 7; 8; 6; 5; 3 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) |
0; 0; 1; 0; 0; 1 | — |
| SECONDARY Number of Participants Who Discontinued From the Study Due to TEAEs |
2; 1; 2; 2; 1; 1 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) |
1; 0; 0; 1; 0; 0 | — |
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
Data sourced from ClinicalTrials.gov (NCT03915496). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.