A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of Multiple Dupilumab Dose Regimens Administered as Monotherapy for Maintaining Treatment Response in Patients With Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 422
- 主要终点
- Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769)
研究概览
简要总结
The primary objective of the study was to assess the ability of different Dupilumab dose regimens, administered as monotherapy, to maintain the treatment response achieved after 16 weeks of initial treatment with Dupilumab monotherapy compared to placebo.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have completed the treatment phase in 1 of the two 16-week initial treatment studies (R668-AD-1334 or R668-AD-1416).
- •Must have achieved at least 1 of the following 2 treatment success criteria:
- •Investigator Global Assessment (IGA) = 0 or 1 (clear or almost clear) at week 16 OR Eczema Area and Severity Index >= 75% (EASI-75) (at least 75% reduction in EASI score from baseline to week 16)
- •Must be willing and able to comply with clinic visits and study-related procedures
- •Must provide signed informed consent
- •Must be able to understand and complete study-related questionnaires
排除标准
- •Receipt of rescue medication for AD in the initial treatment study
- •Any conditions that require permanent discontinuation of study treatment in either initial treatment study
- •Planned or anticipated major surgical procedure during the participants's participation in this study
- •Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during this study
- •Women unwilling to use adequate birth control, if of reproductive potential* and sexually active. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception, whenever engaging in heterosexual intercourse, throughout the duration of the study and for 120 days after last dose of study drug. These include hormonal contraceptives, intrauterine device, or double barrier contraception (e.g, condom + diaphragm), or a male partner with documented vasectomy. Additional requirements for acceptable contraception may apply in certain countries, based on local regulations. Investigators in these countries will be notified accordingly in a protocol clarification letter.
- •(*For females, menopause is defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone level of >= 25 milli units per milliliter (mU/mL) must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception).
研究组 & 干预措施
Placebo
Subcutaneous injection of Placebo (for Dupilumab) was administered once weekly (QW) from Week 1 (Day 1) to Week 36.
干预措施: Placebo (Drug)
Dupilumab 300 mg Q8W
Subcutaneous injection of Dupilumab 300 milligram (mg) alternatively with placebo (matched to Dupilumab) was administered once every eight week (Q8W) from Week 1 to Week 36.
干预措施: Dupilumab (Drug)
Dupilumab 300 mg Q4W
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered once every four week (Q4W) from Week 1 to Week 36.
干预措施: Dupilumab (Drug)
Dupilumab 300 mg Q2W/QW
Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.
干预措施: Dupilumab (Drug)
结局指标
主要结局
Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769)
时间窗: Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study)
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI).
Percentage of Participants With Eczema Area and Severity Index >= 75% [EASI-75] at Baseline of Current Study Maintaining EASI-75 at Week 36
时间窗: Week 36
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved \>=75% overall improvement in EASI score at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder.
次要结局
- Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response Within 1 Point of Baseline at Week 36(Baseline, Week 36)
- Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response at 0 or 1 Point at Week 36(Week 36)
- Percentage of Participants With Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score Increased by 3 or More Points From Baseline to Week 35(Baseline up to Week 35)
- Time to First Event of Investigator's Global Assessment (IGA) >= 2 for Participants With IGA 0 or 1 at Baseline(Baseline up to Week 36)
- Percentage of Participants With Increased Investigator's Global Assessment (IGA) Score 3 or 4 at Week 36(Week 36)
- Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (>= 50% Reduction in EASI Score) at Week 36(Week 36)
- Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 36(Baseline, Week 36)
- Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 36(Baseline, Week 36)
- Absolute Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score at Week 35(Baseline, Week 35)
- Absolute Change From Baseline in Body Surface Area (BSA) Through Week 36(Baseline through Week 36)
- Absolute Change From Baseline Through in Patient Oriented Eczema Measure (POEM) Through Week 36(Baseline through Week 36)
- Absolute Change From Baseline in Dermatology Life Quality Index (DLQI) Through Week 36(Baseline through Week 36)
- Absolute Change From Baseline in Hospital Anxiety Depression Scale (HADS) Through Week 36(Baseline through Week 36)
- Difference Between Current Study Baseline and Week 36 in Percent Change in SCORAD From Parent Study Baseline(Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study))
- Difference Between Current Study Baseline and Week 35 in Percent Change in Peak Weekly Pruritus NRS From Parent Study Baseline(Baseline (Parent Study), Baseline (Current Study) and Week 35 (Current study))
- Annualized Event Rate of Skin Infection Treatment- Emergent Adverse Events (TEAEs)(Baseline through Week 36)
- Annualized Event Rate of Flares(Baseline through week 36)
- Percentage of Well-Controlled Weeks During the On-treatment Period(Baseline through Week 36)