Atopic Dermatitis: A Study of Upadacitinib in Adult Subjects with Moderate-to-Severe Atopic Dermatitis and Inadequate Response to Dupilumab (SWITCH-UP)

JRCT ID: jRCT2061240026

Registered date:21/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Atopic Dermatitis
• Date of first enrollment: 12/07/2024
• Target sample size: 32
• Countries of recruitment: United States of America,Japan,Puerto Rico,Japan,Colombia,Japan,South Korea,Japan
• Study type: Interventional
• Intervention(s): 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 Dose A or dupilumab Dose A. Based on the participants response to upadacitinib Dose A, they may have their dose increased to upadacitinib Dose B 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.

Outcome(s)

• Primary Outcome: Participants who achieve a composite endpoint of both 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) [Time Frame: At Week 8]

Secondary Outcome

Percentage of participants who achieve EASI 90 [Time Frame: At Week 8]
Percentage of participants achieving worst pruritus numerical rating scale (WP-NRS) 0/1 [Time Frame: At Week 8]
Percentage of participants achieving worst pruritus numerical rating scale (WP-NRS) 0/1 [Time Frame: At Week 4]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 63age old
• Gender: Both

Include criteria

-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 >= 16
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) >= 4. 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.
-Documented history of inadequate response to dupilumab treatment after at least 6 months of current use (last dose within 2 weeks prior to Baseline)
-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.

Exclude criteria

-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;
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.
-Participants with current or past history of infection including, Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV)
-Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, (note: include the following only for new protocols) 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; subjects with a history of gastric banding/segmentation are not excluded;
-History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix;

Related Information

• Primary Sponsor: Otani Tetsuya
• Secondary ID(s): NCT06389136