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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 46
- 试验地点
- 11
- 主要终点
- Fold-Change From Baseline in Atopic Dermatitis Biomarkers in Lesional and Non-lesional Skin at Week 12
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
PF-04965842 200 mg
干预措施: PF-04965842 200 mg (Drug)
PF-04965842 100 mg
干预措施: PF-04965842 100 mg (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Fold-Change From Baseline in Atopic Dermatitis Biomarkers in Lesional and Non-lesional Skin at Week 12
时间窗: Baseline, 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.
次要结局
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response ≥ 75% Improvement From Baseline Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, and 12)
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)(Baseline to 16 weeks)
- 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)
- Percentage of Participants Achieving EASI Response ≥ 90% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline to Week 2, 4, 8 and 12)
- Fold-Change From Baseline in Blood Biomarkers for Inflammation and Immune Response at Week 12(Baseline, Week 12)
- Percentage of Participants Achieving EASI Response ≥ 50% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline to Week 2, 4, 8 and 12)
- Percent Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8 and 12(Baseline and Week 2, 4, 8 and 12)
- Number of Participants Who Discontinued From the Study Due to TEAEs(Baseline to 16 weeks)
- 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)
- 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(Baseline, Weeks 2, 4, 8, and 12)
- Number of Participants With Serious Adverse Events (SAEs)(Baseline to 16 weeks)
- Percent-Change From Baseline in T-cell Lymphocyte Subset Populations at Week 12(Baseline, Week 12)
- 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(Baseline, Week 2, 4, 8, 12)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Baseline to 16 weeks)