Clinical trial NCT06389136: A Study of Upadacitinib in Adult Participants With Moderate-to-Severe Atopic Dermatitis and Inadequate Response to Dupilumab
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Upadacitinib
Rinvoq
ABT-494
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-04-29
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 63
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 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. Approximately 300 adult participants ages 18 to 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 94 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.


Eligibility criteria: Inclusion 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) \>= 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.
* 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.

Exclusion 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.
* Chronic AD with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria.- Participants with current or past history of infection including, Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV)
* At Baseline any of the following medical diseases or disorders:

  * 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;

Primary outcomes:
measure: 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)
timeFrame: At Week 8
Secondary outcomes:
measure: Percentage of participants who achieve EASI 90
timeFrame: At Week 8
measure: Percentage of participants achieving worst pruritus numerical rating scale (WP-NRS) 0/1
timeFrame: At Week 8
measure: Percentage of participants achieving worst pruritus numerical rating scale (WP-NRS) 0/1
timeFrame: At Week 4
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Clinical Trials Institute - Northwest Arkansas /ID# 267290
state: Arkansas
city: Encino
country: United States
facility: Private Practice - Dr. Tooraj Raoof /ID# 263849
state: California
city: Mission Viejo
country: United States
facility: Allergy & Asthma Associates of Southern California - Mission Viejo /ID# 266574
state: California
city: Oceanside
country: United States
facility: Dermatologist Medical Group of North County- Profound Research /ID# 266512
state: California
city: Redwood City
country: United States
facility: Stanford University School of Medicine - Redwood City /ID# 263776
state: California
city: Sacramento
country: United States
facility: Integrative Skin Science and Research /ID# 264537
state: California
city: San Diego
country: United States
facility: West Dermatology La Jolla /ID# 265014
state: California
city: Thousand Oaks
country: United States
facility: Clinical Trials Research Institute /ID# 263846
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 263836
state: Connecticut
city: Boca Raton
country: United States
facility: Clearlyderm Dermatology - West Boca /ID# 264923
state: Florida
city: Boca Raton
country: United States
facility: Skin Care Research Boca Raton /ID# 263733
state: Florida
city: Brandon
country: United States
facility: Apex Clinical Trials /ID# 263747
state: Florida
city: Brandon
country: United States
facility: TrueBlue Clinical Research /ID# 265037
state: Florida
city: Coral Springs
country: United States
facility: Life Clinical Trials /ID# 267195
state: Florida
city: Doral
country: United States
facility: Revival Research - Doral /ID# 263541
state: Florida
city: Hollywood
country: United States
facility: Skin Care Research - Hollywood /ID# 263739
state: Florida
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research /ID# 263392
state: Florida
city: Margate
country: United States
facility: GSI Clinical Research, LLC /ID# 263760
state: Florida
city: Miami Lakes
country: United States
facility: Quality Research of South Florida /ID# 266496
state: Florida
city: Miami
country: United States
facility: Research Associates of South Florida /ID# 267291
state: Florida
city: Miami
country: United States
facility: International Dermatology Research /ID# 264961
state: Florida
city: Miami
country: United States
facility: Sullivan Dermatology /ID# 263537
state: Florida
city: Miami
country: United States
facility: Lenus Research and Medical Group /ID# 263779
state: Florida
city: Saint Petersburg
country: United States
facility: Global Clinical Professionals (GCP) /ID# 266474
state: Florida
city: Tampa
country: United States
facility: Skin Care Research - Tampa /ID# 263750
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa /ID# 264531
state: Florida
city: Columbus
country: United States
facility: Centricity Research Columbus Dermatology /ID# 266529
state: Georgia
city: Dawsonville
country: United States
facility: Cleaver Medical Group Dermatology /ID# 263788
state: Georgia
city: Savannah
country: United States
facility: Georgia Skin & Cancer Clinic /ID# 267199
state: Georgia
city: Boise
country: United States
facility: Treasure Valley Medical Research /ID# 263738
state: Idaho
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 264983
state: Illinois
city: Chicago
country: United States
facility: DeNova Research /ID# 264513
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin, LLC /ID# 264534
state: Indiana
city: West Lafayette
country: United States
facility: Options Research Group /ID# 264564
state: Indiana
city: Louisville
country: United States
facility: Dermatology Specialists Research (DS Research) - Kentucky /ID# 263388
state: Kentucky
city: Baton Rouge
country: United States
facility: Velocity Clinical Research at The Dermatology Clinic - Baton Rouge /ID# 267169
state: Louisiana
city: Boston
country: United States
facility: Boston Specialists /ID# 265810
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 263703
state: Massachusetts
city: Quincy
country: United States
facility: Beacon Clinical Research /ID# 263843
state: Massachusetts
city: Bay City
country: United States
facility: Great Lakes Research Group - Bay City /ID# 263535
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center - New Center One /ID# 263522
state: Michigan
city: Flint
country: United States
facility: Onyx Clinical Research - Flint - South Linden Road /ID# 267773
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials /ID# 263579
state: Missouri
city: Lincoln
country: United States
facility: Physician Research Collaboration, LLC /ID# 263583
state: Nebraska
city: Omaha
country: United States
facility: Skin Specialists /ID# 263345
state: Nebraska
city: Reno
country: United States
facility: Skin Cancer and Dermatology Institute - Reno /ID# 263771
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center - Old Etna Road /ID# 263840
state: New Hampshire
city: Kew Gardens
country: United States
facility: Forest Hills Dermatology Group @ Union Turnpike /ID# 263755
state: New York
city: New York
country: United States
facility: Equity Medical, LLC /ID# 265814
state: New York
city: Huntersville
country: United States
facility: Piedmont Plastic Surgery and Dermatology /ID# 266545
state: North Carolina
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute - Tulsa /ID# 263645
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University /ID# 263736
state: Oregon
city: Philadelphia
country: United States
facility: Dermatology Partners /ID# 264972
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center /ID# 264526
state: Pennsylvania
city: Plymouth Meeting
country: United States
facility: Dermatology Associates of Plymouth Meeting /ID# 267286
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina /ID# 263655
state: South Carolina
city: Spartanburg
country: United States
facility: ADCS - Spartanburg /ID# 267185
state: South Carolina
city: Arlington
country: United States
facility: Arlington Research Center, Inc /ID# 263665
state: Texas
city: Austin
country: United States
facility: Orion Clinical Research /ID# 263658
state: Texas
city: Bellaire
country: United States
facility: Bellaire Dermatology Associates /ID# 263794
state: Texas
city: Cypress
country: United States
facility: Studies in Dermatology LLC /ID# 263335
state: Texas
city: Dallas
country: United States
facility: Dermatology Treatment and Research Center /ID# 265812
state: Texas
city: Dallas
country: United States
facility: Modern Research Associates /ID# 263852
state: Texas
city: McAllen
country: United States
facility: The Dermatology Institute of South Texas /ID# 267332
state: Texas
city: Plano
country: United States
facility: Texas Dermatology Research Center /ID# 264528
state: Texas
city: Sugar Land
country: United States
facility: Stride Clinical Research /ID# 267331
state: Texas
city: The Woodlands
country: United States
facility: The Woodlands Dermatology Associates /ID# 266547
state: Texas
city: Tyler
country: United States
facility: Dermatology Associates of Tyler /ID# 264980
state: Texas
city: Morgantown
country: United States
facility: West Virginia Research Institute - Morgantown /ID# 264930
state: West Virginia
city: Calgary
country: Canada
facility: Dermatology Research Institute - Blackfoot Trail /ID# 270450
state: Alberta
city: Edmonton
country: Canada
facility: Stratica Medical /ID# 270466
state: Alberta
city: Québec
country: Canada
facility: Centre de Recherche Saint-Louis /ID# 271083
state: Quebec
city: Medellín
country: Colombia
facility: Centro de Inmunología y Genética CIGE SAS /ID# 266200
state: Antioquia
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatología del Caribe SAS - Circaribe SAS /ID# 265088
state: Atlantico
city: Bogotá
country: Colombia
facility: Centro de Investigacion en Reumatologia y especialidades Medicas S.A.S- CIREEM /ID# 265092
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Unidad Integral de Endocrinologia (UNIENDO) /ID# 266970
state: Cundinamarca
city: Ichinomiya
country: Japan
facility: Ichinomiya Municipal Hospital /ID# 265068
state: Aichi
city: Marugame
country: Japan
facility: Takeoka Dermatology Clinic /ID# 264055
state: Kagawa
city: Kurashiki
country: Japan
facility: Kawasaki Medical School Hospital /ID# 266164
state: Okayama
city: Mibu
country: Japan
facility: Dokkyo Medical University Hospital /ID# 265431
state: Tochigi
city: Tachikawa-shi
country: Japan
facility: Tachikawa Dermatology Clinic /ID# 271912
state: Tokyo
city: Kagoshima
country: Japan
facility: Katahira Dermatology Urology Clinic /ID# 264403
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo /ID# 265104
city: Tokyo
country: Japan
facility: Teikyo University Hospital /ID# 265126
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital /ID# 263330
state: Gyeonggido
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon /ID# 263331
state: Gyeonggido
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital /ID# 263328
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 263329
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center /ID# 263327
state: Seoul Teugbyeolsi
city: Bayamon
country: Puerto Rico
facility: SCB Research Center /ID# 263217
city: Caguas
country: Puerto Rico
facility: Private Practice - Dr. Samuel Sanchez /ID# 263199
city: Carolina
country: Puerto Rico
facility: Private Practice - Dr. Alma Cruz /ID# 263216
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico /ID# 263197
city: San Juan
country: Puerto Rico
facility: GCM Medical Group, PSC /ID# 263218
city: San Juan
country: Puerto Rico
facility: Caribbean Medical Research Center /ID# 267163
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: