A Phase 3b/4 Randomized, Open-label, Efficacy Assessor-Blinded Study, to Evaluate the Efficacy and Safety of Upadacitinib for the Treatment of Adult Subjects With Moderate to Severe Atopic Dermatitis and Inadequate Response to Dupilumab (SWITCH-UP)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 227
- 主要终点
- Participants who achieve at least a 90% reduction in Eczema Area and Severity Index from Baseline (EASI 90)
研究概览
简要总结
Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. Therapies spread over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study aims to provide data on the efficacy and safety of upadacitinib at different doses in adult participants with moderate to severe AD.
Upadacitinib is an approved drug for the treatment of moderate to severe atopic dermatitis (AD). This study is conducted in 2 periods. During Period 1, participants are randomly assigned into 1 of 2 groups called treatment arms to receive upadacitinib 15mg or dupilumab 300mg. Based on the participants response to upadacitinib 15mg, they may have their dose increased to upadacitinib 30mg after 2 weeks. In Period 2, participants that completed Period 1 will either remain on their assigned dose or be reassigned to a different dose based on their Eczema Area and Severity Index (EASI) response. Approximately 200 adult participants ages 18 to less than 64 with moderate to severe AD who are current users of dupilumab and had a history of inadequate response to dupilumab will be enrolled at up to 130 sites worldwide.
The study is comprised of a 35-day Screening Period, an 8-week Open-Label Period 1 and a 24-week Open-Label Period 2 for participants that completed Period 1. Participants will receive upadacitinib oral tablets once daily or dupilumab subcutaneous (SC) injection every other week for 32 weeks and followed for 30 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 63 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic AD with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria.
- •Participant meets all the following disease activity criteria at Baseline Visit:
- •Eczema Area and Severity Index (EASI) score >= 12;
- •validated Investigator´s Global Assessment for AD (vIGA-AD) score >= 3;
- •Body surface area (BSA) involvement of >= 10% in a majority of subjects (>= 50% of the overall study population)
- •Baseline weekly average of daily Worst Pruritus-Numerical Rating Scale (WP-NRS) >=
- •Note: The Baseline weekly average of daily WP-NRS will be calculated from the 7 consecutive days immediately preceding the Baseline Visit. A minimum of 4 daily scores out of the 7 days is needed.
- •Inadequate response to dupilumab treatment after at least 4 months of current use.
- •Particpant has applied a topical emollient (an additive-free, bland emollient moisturizer) twice daily for at least 7 days before the Baseline Visit and for the duration of the study. Note: Subject may use prescription moisturizers or moisturizers containing ceramide, urea, filaggrin degradation products or hyaluronic acid if such moisturizers were initiated before the Screening visit.
排除标准
- •Meeting any of the following conditions at Baseline:
- •Other active skin diseases or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline Visit or would interfere with assessment of AD lesions;
- •Two or more past episodes of herpes zoster, or one or more episodes of disseminated herpes zoster;
- •One or more past episodes of disseminated herpes simplex (including eczema herpeticum);
- •HIV infection defined as confirmed positive anti- HIV Ab test;
- •Participants with current or past history of infection including, Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV);
- •Active TB or meet TB exclusionary parameters (specific requirements for TB testing are provided in the operations manual);
- •For Japan: Positive result of beta-D-glucan (screening for Pneumocystis jirovecii infection) or two consecutive indeterminate results of beta-D-glucan during the Screening Period;
- •Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit;
- •Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the subject an unsuitable candidate for the study;
- •COVID-19 infection: In subjects who tested positive for COVID-19, at least 5 days must have passed between a COVID-19 positive test result and the Baseline visit of asymptomatic subjects. Subjects with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Subjects may be rescreened if deemed appropriate by the investigator based upon the subject's health status.
- •At Baseline any of the following medical diseases or disorders:
- •Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery or venous thromboembolism;
- •Any unstable clinical condition which, in the opinion of the investigator would put the subject at risk by participating in the protocol;
- •Diagnosed active parasitic infection, suspected or high risk of parasitic infection unless clinical (and if necessary) laboratory assessment have ruled out active infection before randomization;
- •History of an organ transplant which requires continued immunosuppression;
- •History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class;
- •History of GI perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment;
- •Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery including sleeve gastrectomy; subjects with a history of gastric banding/segmentation are not excluded;
- •History of malignancy except for successfully treated NMSC or localized carcinoma in situ of the cervix.
研究组 & 干预措施
Period 2 Open Label: Dupilumab ≥ EASI 75 Response
Participants that were receiving Dupilumab 300mg and completed Period 1, will continue to receive Dupilumab 300mg SC injection in Period 2 with a clinical response of ≥ EASI 75 at Week 8
干预措施: Dupilumab 300mg Dose (Drug)
Period 1: Upadacitinib Open Label Treatment
Participants randomly assigned to receive Upadacitinib 15mg tablet once per day.
Based on clinical response, participants randomized to Upadacitinib 15mg may have their dose increased to Upadacitinib 30mg starting at Week 2.
干预措施: Upadacitinib 30mg Dose (Drug)
Period 1: Upadacitinib Open Label Treatment
Participants randomly assigned to receive Upadacitinib 15mg tablet once per day.
Based on clinical response, participants randomized to Upadacitinib 15mg may have their dose increased to Upadacitinib 30mg starting at Week 2.
干预措施: Upadacitinib 15mg Dose (Drug)
Period 1: Dupilumab Open Label Treatment
Participants randomly assigned to receive Dupilumab 300mg SC injection once every other week for 8 weeks.
干预措施: Dupilumab 300mg Dose (Drug)
Period 2 Open Label: Upadacitinib < EASI 75 response
Participants that were receiving Upadacitinib 15mg or 30mg and completed Period 1, will be allocated or continue to receive oral doses of Upadacitinib 30mg in Period 2 with a clinical response of < EASI 75 at Week 8
干预措施: Upadacitinib 30mg Dose (Drug)
Period 2 Open Label: Upadacitinib ≥ EASI 75 Response
Participants that were receiving Upadacitinib 15mg or 30mg and completed Period 1, will continue to receive the same oral doses of Upadacitinib in Period 2 with a clinical response of ≥ EASI 75 at Week 8
干预措施: Upadacitinib 15mg Dose (Drug)
Period 2 Open Label: Upadacitinib ≥ EASI 75 Response
Participants that were receiving Upadacitinib 15mg or 30mg and completed Period 1, will continue to receive the same oral doses of Upadacitinib in Period 2 with a clinical response of ≥ EASI 75 at Week 8
干预措施: Upadacitinib 30mg Dose (Drug)
Period 2 Open Label Period: Dupilumab < EASI 75 Response
Participants that were receiving Dupilumab 300mg SC injections and completed Period 1, will receive oral doses of Upadacitinib 15mg in Period 2 with a clinical response of < EASI 75 at Week 8
干预措施: Upadacitinib 15mg Dose (Drug)
结局指标
主要结局
Participants who achieve at least a 90% reduction in Eczema Area and Severity Index from Baseline (EASI 90)
时间窗: At Week 8
The EASI is a validated measure used to assess the severity and extent of AD. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) are each assessed for severity by the investigator on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). The EASI score ranges from 0-72 points with an MCID of 6.6 points.
次要结局
- Participants who simultaneous achieve at least a 90% reduction in Eczema Area and Severity Index from Baseline (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1)(At Week 8)
- Percentage of participants who achieve a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1)(At Week 8)
- Participants who simultaneous achieve at least a 90% reduction in Eczema Area and Severity Index from Baseline (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1)(At Week 8)
- Percentage of participants achieving worst pruritus numerical rating scale (WP-NRS) 0/1(At Week 4)