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

Atopic Dermatitis Clinical Trial

— JADE MOA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03915496
• Other study ID #: B7451037
• Secondary ID: JADE MOA
• Status: Completed
• Phase: Phase 2
• Start date: June 18, 2020
• Est. completion date: November 16, 2021

Study information

• Verified date: January 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: November 16, 2021
• Est. primary completion date: November 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• PF-04965842 200 mg
PF-04965842 200 mg administered as two tablets to be taken orally once daily for 12 weeks
• PF-04965842 100 mg
PF-04965842 100 mg administered as two tablets to be taken orally once daily for 12 weeks
• Placebo
Placebo administered as two tablets to be taken orally once daily for 12 weeks

Locations

Country	Name	City	State
Canada	Beacon Dermatology	Calgary	Alberta
Canada	Innovaderm Research, Inc.	Montreal	Quebec
United States	Menter Dermatology Research Institute	Dallas	Texas
United States	Wayne Health - Wayne State Dermatology	Dearborn	Michigan
United States	California Dermatology & Clinical Research Institute	Encinitas	California
United States	Olympian Clinical Research	Largo	Florida
United States	Keck School of Medicine of USC - IDS Pharmacy	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	The Indiana Clinical Trials Center, PC - Dermatology Research	Plainfield	Indiana
United States	ForCare Clinical Research	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Erythrocytes at Week 2, 4, 8 and 12	Clinical laboratory tests including red blood cell (erythrocytes) were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in Reticulocytes at Week 2, 4, 8 and 12	Clinical laboratory tests including reticulocytes were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in Platelet Counts at Week 2, 4, 8 and 12	Clinical laboratory tests including platelet counts were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Week 2, 4, 8 and 12	Clinical laboratory tests including hs-CRP were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in Interleukin 6 at Week 2, 4, 8 and 12	Clinical laboratory tests including interleukin were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in Erythropoietin at Week 2, 4, 8 and 12	Clinical laboratory tests including erythropoietin were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in Thrombopoietin at Week 2, 4, 8 and 12	Clinical laboratory tests including thrombopoietin were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.	Baseline and Week 2, 4, 8 and 12
Other	Change From Baseline in Night Time Itch Scale Score at Week 2, 4, 8 and 12	The severity and frequency of itch (pruritus) during the night due to AD was assessed using the Night Time Itch Scale Score. Participants assessed their worst itching due to AD during their most recent night's sleep on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Higher scores indicated worse itch. The frequency of itch was assessed using a 5-point qualitative scale, with responses including "Never", "Rarely", "Sometimes", "Often" and "Almost Always".	Baseline and Week 2, 4, 8 and 12
Other	Plasma PF-04965842 Concentration	Pharmacokinetic (PK) samples were collected at Week 4 and 12 for measurement of plasma concentration of PF-04965842.	Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
Other	Plasma PF-06471658 (M1) Concentration	PK samples were collected at Week 4 and 12 for measurement of plasma concentration of abrocitinib's metabolite PF-06471658 (M1).	Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
Other	Plasma PF-07055087 (M2) Concentration	PK samples were collected at Week 4 and 12 for measurement of plasma concentration of abrocitinib's metabolite PF-07055087 (M2).	Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
Other	Plasma PF-07054874 (M4) Concentration	PK samples were collected at Week 4 and 12 for measurement of plasma concentration of abrocitinib's metabolites PF-07054874 (M4).	Day 29 Hour 0 (prior to dosing) and 30 miniute post-dose, Day 85 30 minute and Hour 4 post-dose
Primary	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	Fold-Change From Baseline in Cellular (T-cell and Dendritic Cell) Inflammation Markers at Week 12	Mean fold-changes from baseline in immunohistochemistry analysis in lesional skin endpoints at Week 12 are presented. Fold-changes are computed by obtaining the antilog of log2 fold-changes, retaining the sign for log2 fold-change.	Baseline, Week 12
Secondary	Fold-Change From Baseline in Epidermal Hyperplasia Markers in Skin Biopsies and Skin Thickness at Week 12	Mean fold-changes from baseline in hyperplasia markers in skin biopsies at Week 12 are presented. Fold-changes are computed by obtaining the antilog of log2 fold-changes, retaining the sign for log2 fold-change.	Baseline, Week 12
Secondary	Fold-Change From Baseline in Blood Biomarkers for Inflammation and Immune Response at Week 12	OLINK Proteomics Microassay was used to analyze biomarkers in serum to assess the effect of abrocitinib on the blood biomarkers. Mean fold-changes at Week 12 from baseline are listed. Baseline is defined as the last observation on or prior to day of first dose (Day 1).	Baseline, Week 12
Secondary	Percent-Change From Baseline in T-cell Lymphocyte Subset Populations at Week 12	Mean percent changes from baseline at Week 12 in T-cell lymphocyte subset populations (CD3+ T cells, CD4+ T cells, CD8+ T cells, NK cells, B cells) are presented. Baseline is defined as the last observation on or prior to day of first dose (Day 1).	Baseline, Week 12
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	PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Participants who withdrew from the study were counted as non-responder. Spearman correlation coefficient was calculated to assess the relationship between PP-NRS CFB and fold CFB of IHC and gene expression biomarkers.	Baseline, Week 12
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	The IGA of AD is scored on a 5-point scale (0-4), reflecting a global consideration of the erythema, induration and scaling. The overall severity of AD was assessed according to the 5-point scale: 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 4=Severe. Participants who withdrew from the study were counted as non-responder.	Baseline, Weeks 2, 4, 8, and 12
Secondary	Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response = 75% Improvement From Baseline Week 2, 4, 8 and 12	The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.	Baseline, Week 2, 4, 8, and 12
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	PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Higher scores indicated worse itch. Participants who withdrew from the study were counted as non-responder.	Baseline, Week 2, 4, 8, 12
Secondary	Percentage of Participants Achieving EASI Response = 90% Improvement From Baseline at Week 2, 4, 8 and 12	The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.	Baseline to Week 2, 4, 8 and 12
Secondary	Percentage of Participants Achieving EASI Response = 50% Improvement From Baseline at Week 2, 4, 8 and 12	The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.	Baseline to Week 2, 4, 8 and 12
Secondary	Percent Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8 and 12	BSA efficacy is derived from the sum of the BSA in handprints across 4 body regions assessed as part of the EASI assessment. Handprint refers to that of each individual participant for their own measurement. The BSA efficacy ranges from 0 to 100%, with higher values representing greater severity of AD. The percentage BSA ranges from 0 to 100, with higher scores representing greater severity of AD. Since the scalp, palms, and soles were excluded from the BSA (efficacy) assessment, the maximum possible percentage BSA was less than 100.	Baseline and Week 2, 4, 8 and 12
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs that occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.	Baseline to 16 weeks
Secondary	Number of Participants With Serious Adverse Events (SAEs)	A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.	Baseline to 16 weeks
Secondary	Number of Participants Who Discontinued From the Study Due to TEAEs	An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs that occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.	Baseline to 16 weeks
Secondary	Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	Laboratory tests included hematology (including coagulation panel), clinical chemistry, lipid profile panel, and routine urinalysis. LLN is lower limit of normal. ULN is upper limit of normal.	Baseline to 16 weeks

External Links

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