Upadacitinib for Eczema

(Switch-Up Trial)

Recruiting at 85 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Must be taking: Dupilumab

Disqualifiers: HIV, Active TB, Hepatitis B/C, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants must have an inadequate response to dupilumab, suggesting that you may need to continue using it. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug Upadacitinib for eczema?

Upadacitinib has shown high effectiveness in treating moderate-to-severe atopic dermatitis (a type of eczema) in several studies, including its use with topical corticosteroids, and it is approved in Japan for this condition. ^{1 2 3 4 5}

Is upadacitinib safe for humans?

Upadacitinib, also known as Rinvoq or ABT-494, has been studied for safety in people with moderate-to-severe atopic dermatitis. The most common side effect reported is acne, but it has been generally well-tolerated in clinical trials. ^{1 2 3 6 7}

Is the drug Upadacitinib a promising treatment for eczema?

The provided research articles do not contain information about Upadacitinib or its effectiveness for treating eczema. Therefore, based on the given data, we cannot determine if Upadacitinib is a promising treatment for eczema. ^{8 9 10 11 12}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults aged 18-64 with moderate to severe atopic dermatitis (AD) who haven't responded well to Dupilumab. Participants must not have certain infections, a history of severe herpes, active tuberculosis, other skin diseases requiring systemic treatment, or HIV. Those recently infected with COVID-19 must meet specific recovery criteria.

Inclusion 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 (calculated from the 7 consecutive days immediately preceding the Baseline Visit with a minimum of 4 daily scores out of the 7 days), Documented history of inadequate response to dupilumab treatment after at least 6 months of current use (last dose within 2 weeks prior to Baseline), Participant 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 (subject may use prescription moisturizers or moisturizers containing ceramide, urea, filaggrin degradation products or hyaluronic acid if initiated before the Screening visit)

I have had chronic atopic dermatitis for over 3 years and meet specific medical criteria.

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, Positive result of beta-D-glucan (screening for Pneumocystis jirovecii infection) or two consecutive indeterminate results of beta-D-glucan during the Screening Period (for Japan), 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), 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 (include only for new protocols), 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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment Period 1

Participants receive upadacitinib Dose A or dupilumab Dose A. Dose may be increased based on response.

8 weeks

Regular visits at a hospital or clinic

Treatment Period 2

Participants continue or adjust treatment based on EASI response.

24 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Upadacitinib (Janus Kinase (JAK) Inhibitor)

Trial Overview The trial is testing the effectiveness and safety of Upadacitinib at two different doses in adults with AD that's hard to treat. It involves an initial period where participants receive one dose level followed by a possible adjustment after 2 weeks based on their response.

Participant Groups

Group I: Period 2 Open Label: Upadacitinib ≥ EASI 75 Response Experimental Treatment 2 Interventions

Participants that were receiving Upadacitinib Dose A or Dose B 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

Group II: Period 2 Open Label: Upadacitinib < EASI 75 response Experimental Treatment 1 Intervention

Participants that were receiving Upadacitinib Dose A or Dose B and completed Period 1, will be allocated or continue to receive oral doses of Upadacitinib Dose B in Period 2 with a clinical response of \< EASI 75 at Week 8

Group III: Period 2 Open Label: Dupilumab ≥ EASI 75 Response Experimental Treatment 1 Intervention

Participants that were receiving Dupilumab Dose A and completed Period 1, will continue to receive Dupilumab Dose A SC injection in Period 2 with a clinical response of ≥ EASI 75 at Week 8

Group IV: Period 2 Open Label Period: Dupilumab < EASI 75 Response Experimental Treatment 1 Intervention

Participants that were receiving Dupilumab Dose A and completed Period 1, will receive oral doses of Upadacitinib Dose A in Period 2 with a clinical response of \< EASI 75 at Week 8

Group V: Period 1: Upadacitinib Open Label Treatment Experimental Treatment 2 Interventions

Participants randomly assigned to receive Upadacitinib Dose A tablet once per day. Based on clinical response, participants randomized to Upadacitinib Dose A will have their dose increased to Upadacitinib Dose B starting at Week 2.

Group VI: Period 1: Dupilumab Open Label Treatment Experimental Treatment 1 Intervention

Participants randomly assigned to receive Dupilumab Dose A SC injection once every other week for 8 weeks.

Upadacitinib is already approved in Canada for the following indications:

Approved in Canada as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a study of 65 Japanese patients with moderate-to-severe atopic dermatitis, upadacitinib significantly reduced skin rash severity across all anatomical sites after 4, 12, and 24 weeks of treatment.

The treatment was particularly effective for lower limbs, achieving higher rates of improvement compared to the trunk and head and neck areas, indicating varying responsiveness based on the body site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis. Hagino, T., Saeki, H., Fujimoto, E., et al.[2023]

In a study of 38 patients, upadacitinib demonstrated significant effectiveness in treating atopic dermatitis (AD) and hand eczema (HE), with 50% of patients achieving a 75% improvement in eczema severity (EASI-75) by Week 16.

The safety profile of upadacitinib was consistent with previous clinical trials, indicating it is a safe option for patients with AD and concomitant HE, with no new adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the BioDay registry. Kamphuis, E., Loman, L., Han, HL., et al.[2023]

Upadacitinib, a selective JAK inhibitor, was well tolerated in a study involving 2485 patients (including 333 adolescents) with moderate-to-severe atopic dermatitis, treated for an average of about one year.

The safety profile showed no new significant risks, with common adverse events being mild, such as acne, and serious adverse events occurring at rates similar to those expected in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies. Guttman-Yassky, E., Thyssen, JP., Silverberg, JI., et al.[2023]

In a study of 901 patients with moderate-to-severe atopic dermatitis, upadacitinib combined with topical corticosteroids (TCS) showed sustained efficacy over 52 weeks, with 50.8% and 69.0% of patients achieving significant skin improvement (EASI-75) at the lower and higher doses, respectively.

The treatment was well tolerated, with no new safety risks identified over the year-long study, and serious adverse events were rare, indicating a favorable long-term safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results. Silverberg, JI., de Bruin-Weller, M., Bieber, T., et al.[2022]

In a real-life study of 29 patients with severe atopic dermatitis, 79.3% achieved clear or almost clear skin after treatment with upadacitinib for about 54 weeks, demonstrating its effectiveness especially in patients who had previously failed other treatments.

The safety profile of upadacitinib was reassuring, with lipid changes being the most common adverse event, indicating that while monitoring is necessary, the treatment is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Effectiveness and Tolerance of Upadacitinib for Severe Atopic Dermatitis in Adolescents and Adults. De Greef, A., Ghislain, PD., de Montjoye, L., et al.[2023]

In a real-world study of 43 adults with atopic dermatitis who had previously failed other treatments, including dupilumab, upadacitinib showed rapid and significant improvements in disease severity, with 97.5% of patients achieving at least a 75% reduction in eczema severity by week 16.

The treatment also led to substantial improvements in patients' quality of life, with 76.9% reporting minimal symptoms by week 16, confirming upadacitinib's effectiveness and safety in a population not previously studied in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study. Chiricozzi, A., Gori, N., Narcisi, A., et al.[2022]

In a post hoc analysis of three phase 3 trials involving 2583 patients, acne was identified as a common side effect of upadacitinib treatment for atopic dermatitis, affecting 9.8% of patients on 15 mg, 15.2% on 30 mg, and 2.2% on placebo.

Most cases of acne were mild to moderate and did not significantly affect patient quality of life, with many cases requiring no treatment or being managed effectively with topical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials. Mendes-Bastos, P., Ladizinski, B., Guttman-Yassky, E., et al.[2022]

Patients with newly diagnosed BRAFV600-mutant metastatic melanoma have better survival rates at 2 years when treated with the combination of immunotherapies nivolumab and ipilimumab compared to targeted therapies dabrafenib and trametinib.

These findings suggest that the combination of nivolumab and ipilimumab may establish a new standard for first-line treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy First for BRAF-Mutant Melanoma. [2022]

Cutaneous reactions, which are skin-related side effects, are common in pediatric patients undergoing targeted therapies, particularly those that focus on specific receptors and signaling pathways.

The literature provides substantial data on the timing, severity, and treatment strategies for skin reactions associated with BRAF, MEK, and EGFR inhibitors, indicating a need for awareness and management in pediatric dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supportive Oncodermatology in Pediatric Patients. Linggonegoro, DW., Song, H., Huang, JT.[2022]

Dabrafenib is an effective targeted therapy for advanced melanoma patients with BRAF V600E mutations, showing response rates of about 50% and a progression-free survival of 6 months.

Combining dabrafenib with the MEK inhibitor trametinib significantly improves both progression-free survival and overall survival compared to dabrafenib alone, and it is also being studied for effectiveness in other BRAF-mutated solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib in the treatment of advanced melanoma. Medina, T., Amaria, MN., Jimeno, A.[2017]

In a study of 14 patients treated with dabrafenib and trametinib for an average of 24 weeks, all patients experienced at least one skin-related side effect, with papillomas being the most common.

The combination therapy can lead to serious skin issues, including the development of squamous cell carcinoma, highlighting the need for careful monitoring and management of these adverse effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib. Lacroix, JP., Wang, B.[2017]

Cutaneous melanomas should be excised with 1- to 2-cm safety margins, and sentinel lymph node dissection is recommended for patients with thicker tumors, although its survival benefit is still unclear.

For stage III/IV melanoma, the primary treatment options include anti-PD-1 therapies for all patients and BRAF/MEK inhibitors specifically for those with BRAF mutations, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2019. Garbe, C., Amaral, T., Peris, K., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the BioDay registry. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Real-Life Effectiveness and Tolerance of Upadacitinib for Severe Atopic Dermatitis in Adolescents and Adults. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy First for BRAF-Mutant Melanoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Supportive Oncodermatology in Pediatric Patients. [2022]

10. Spain pubmed.ncbi.nlm.nih.gov

Dabrafenib in the treatment of advanced melanoma. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib. [2017]

12. England pubmed.ncbi.nlm.nih.gov

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2019. [2020]