A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and Triamcinolone 0.1% Cream-Controlled Study to Evaluate the Safety and Efficacy of INCB018424 Phosphate Cream Applied Topically to Adults With Atopic Dermatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 307
- 试验地点
- 52
- 主要终点
- Mean Percentage Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 4 in Participants Treated With Ruxolitinib 1.5% Cream Twice a Day (BID) Compared With Participants Treated With Vehicle Cream BID
研究概览
简要总结
The purpose of this study is to establish the efficacy of each strength of ruxolitinib cream once daily (QD) or twice daily (BID) in participants with atopic dermatitis as compared with vehicle cream BID.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants diagnosed with atopic dermatitis (AD) as defined by the Hanifin and Rajka criteria.
- •Participants with a history of AD for at least 2 years.
- •Participants with an Investigator's Global Assessment (IGA) score of 2 to 3 at screening and baseline.
- •Participants with body surface area (BSA) of AD involvement, excluding the face and intertriginous areas, of 3% to 20% at screening and baseline.
- •Participants who agree to discontinue all agents used to treat AD from screening through the final follow-up visit.
排除标准
- •Participants with evidence of active acute or chronic infections.
- •Use of topical treatments for AD (other than bland emollients) within 2 weeks of baseline.
- •Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 4 weeks or 5 half-lives of baseline (whichever is longer).
- •Participants with other dermatologic disease besides AD whose presence or treatments could complicate the assessment of disease (eg, psoriasis).
- •Participants with a history of other diseases besides dermatologic disorders (eg, other autoimmune diseases) taking treatments that could complicate assessments.
- •Participants with cytopenias at screening, defined as:
- •Leukocytes < 3.0 × 10^9/L.
- •Neutrophils < lower limit of normal.
- •Hemoglobin < 10 g/dL.
- •Lymphocytes < 0.8 × 10^9/L
- •Platelets < 100 × 10^9/L.
- •Participants with severely impaired liver function (Child-Pugh Class C) or end-stage renal disease (ESRD) on dialysis or at least 1 of the following:
- •Serum creatinine > 1.5 mg/dL.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 × upper limit of normal.
- •Participants taking potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 5 half-lives, whichever is longer, before the baseline visit (topical agents with limited systemic availability are permitted).
- •Participants who have previously received Janus kinase (JAK) inhibitors, systemic or topical (e.g., ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib).
研究组 & 干预措施
DB: Ruxolitinib 1.5% BID
Participants applied ruxolitinib 1.5% cream BID for 8 weeks in DB period.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
Double Blind (DB): Vehicle BID
Participants applied vehicle cream twice daily (BID) for 8 weeks DB period.
干预措施: Vehicle Cream BID (Drug)
DB: Triamcinolone (TAC) 0.1% BID/Vehicle Cream BID
Participants applied triamcinolone 0.1% cream BID for 4 weeks followed by vehicle cream for 4 weeks in DB period.
干预措施: Triamcinolone 0.1% Cream BID (Drug)
DB: Triamcinolone (TAC) 0.1% BID/Vehicle Cream BID
Participants applied triamcinolone 0.1% cream BID for 4 weeks followed by vehicle cream for 4 weeks in DB period.
干预措施: Vehicle Cream BID (Drug)
DB: Ruxolitinib 0.15% Once Daily (QD)
Participants applied ruxolitinib 0.15% cream QD for 8 weeks in DB period.
干预措施: Ruxolitinib 0.15% Cream QD (Drug)
DB: Ruxolitinib 0.5% QD
Participants applied ruxolitinib 0.5% cream QD for 8 weeks in DB period.
干预措施: Ruxolitinib 0.5% Cream QD (Drug)
DB: Ruxolitinib 1.5% QD
Participants applied ruxolitinib 1.5% cream QD for 8 weeks in DB period.
干预措施: Ruxolitinib 1.5% Cream QD (Drug)
Open-Label (OL): Vehicle BID to Ruxolitinib 1.5% BID
Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
OL: TAC BID/Vehicle BID to Ruxolitinib 1.5% BID
Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
OL: Ruxolitinib 0.15% QD to Ruxolitinib 1.5% BID
Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
OL: Ruxolitinib 0.5% QD to Ruxolitinib 1.5% BID
Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
OL: Ruxolitinib 1.5% QD to Ruxolitinib 1.5% BID
Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
OL: Ruxolitinib 1.5% BID to Ruxolitinib 1.5% BID
Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
干预措施: Ruxolitinib 1.5% Cream BID (Drug)
结局指标
主要结局
Mean Percentage Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 4 in Participants Treated With Ruxolitinib 1.5% Cream Twice a Day (BID) Compared With Participants Treated With Vehicle Cream BID
时间窗: Baseline and Week 4
EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.
次要结局
- Time to Achieve EASI-50(From Baseline to Week 8)
- Percentage Change From Baseline in EASI Score at Week 4(Baseline and Week 4)
- Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD Compared With Participants Treated With Vehicle Cream BID(Baseline and Week 4)
- Number of Participants With At Least One Adverse Event (AEs) and as Per Severity(Up to Week 24)
- Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD/BID Cream Compared With Participants Treated With Triamcinolone 0.1% Cream BID Followed by Vehicle(Baseline and Week 4)
- Percentage of Participants Who Achieve a ≥ 50% Improvement From Baseline in EASI (EASI-50) at Weeks 2, 4, and 8(Week 2, 4 and 8)
- Mean Percentage Change From Baseline in EASI Score at Week 2 and Week 8(Baseline, Week 2 and 8)
- Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of 0 to 1 Who Have an Improvement of ≥ 2 Points From Baseline at Weeks 2, 4, and 8(Week 2, 4 and 8)
- Mean Change From Baseline in the Itch Numerical Rating Scale (NRS) Score at Weeks 2, 4, and 8(Baseline, Week 2, 4 and 8)