Upadacitinib + Topical Corticosteroids for Eczema

(AD Up Trial)

Enrolling by invitation at 221 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Topical corticosteroids

Must not be taking: Janus kinase inhibitors

Disqualifiers: Other skin diseases, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of upadacitinib, a pill, and topical corticosteroids (creams) to determine their effectiveness in treating moderate to severe eczema, a skin condition causing itchy, inflamed patches. Researchers aim to assess whether this combination is safe and more effective than other treatments for individuals who haven't found success with creams alone. Participants will be divided into groups, with some receiving different doses of upadacitinib alongside the creams, while others will start with a placebo (inactive pill). This trial suits those aged 12 and up who have had chronic eczema for at least 3 years, with significant skin involvement and itching that hasn't improved with typical treatments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop their current atopic dermatitis treatments before joining the study. If you are unable or unwilling to do so, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that upadacitinib, when combined with topical corticosteroids (TCS), is generally safe for treating moderate to severe atopic dermatitis (AD). Studies have found that both the 15 mg and 30 mg doses of upadacitinib are safe for individuals with this condition. No new safety concerns have emerged, and the safety profile aligns with previous research.

However, upadacitinib can increase the risk of infections, and some individuals may develop infections requiring medical attention. This risk should be considered when deciding to join a trial.

The FDA has already approved upadacitinib for treating AD in certain patients, supporting its known safety. Trial participants will receive either 15 mg or 30 mg of upadacitinib, along with TCS, which are common and well-understood treatments for skin inflammation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Upadacitinib is unique because it targets a specific enzyme called Janus kinase (JAK), which plays a key role in the inflammatory process associated with eczema. Unlike standard treatments that primarily involve topical corticosteroids or immunosuppressants like cyclosporine, upadacitinib offers a new mechanism of action by directly inhibiting JAK pathways. Researchers are excited about this treatment because it has the potential to offer relief to patients who have not responded well to traditional therapies, and it may provide a more targeted approach with potentially fewer side effects compared to broader immunosuppressive treatments. Additionally, the option to combine upadacitinib with topical corticosteroids could enhance overall effectiveness and flexibility in managing eczema symptoms.

What evidence suggests that this trial's treatments could be effective for atopic dermatitis?

Research has shown that upadacitinib, when combined with topical corticosteroids, effectively treats moderate to severe eczema. In this trial, participants will receive either a 15 mg or 30 mg dose of upadacitinib alongside topical corticosteroids. Studies have found that patients using upadacitinib experience significant improvements, such as reduced itchiness and clearer skin. Specifically, both 15 mg and 30 mg doses of upadacitinib have led to major improvements, with many patients seeing at least a 75% improvement in their symptoms. Additionally, some studies have shown that upadacitinib is more effective than other treatments like Dupixent, offering hope for a better quality of life. These findings suggest that upadacitinib could be a promising treatment option for those dealing with eczema. ^{2 3 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adolescents and adults with moderate to severe atopic dermatitis (eczema) who haven't responded well to standard creams or need systemic treatment. Participants should have a significant area of skin affected, intense itchiness, and a history of the condition for at least 3 years. They must weigh over 40 kg if under 18. Not eligible if they've used JAK inhibitors before, can't stop current eczema treatments, have other major skin conditions/infections, or are pregnant/breastfeeding.

Inclusion Criteria

I have used a moisturizer twice a day for at least a week.

I've tried creams or pills for my skin condition without success.

I have had chronic eczema for over 3 years.

Exclusion Criteria

I cannot or do not want to stop my current eczema treatments before the study.

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I do not need medications that are not allowed in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment

Participants receive upadacitinib or placebo in combination with topical corticosteroids

16 weeks

Blinded Extension

Participants continue treatment with upadacitinib in a blinded extension period

244 weeks

Long-term Extension

Participants have the opportunity to enroll in a blinded long-term extension period

264 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Topical corticosteroids (TCS)
• Upadacitinib

Trial Overview The trial is testing Upadacitinib pills combined with topical corticosteroids against placebo pills with topical corticosteroids in people with stubborn eczema to see which is better at reducing symptoms like redness and itching.

How Is the Trial Designed?

Group I: Upadacitinib 30 mg QD + Topical Corticosteroids Experimental Treatment 2 Interventions

Participants will receive upadacitinib 30 mg orally once a day for up to 260 weeks. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.

Group II: Upadacitinib 15 mg QD + Topical Corticosteroids Experimental Treatment 2 Interventions

Participants will receive upadacitinib 15 mg orally once a day for up to 260 weeks. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.

Group III: Long-Term Extension Experimental Treatment 2 Interventions

Participants who reach Week 260 in Studies M16-045, M18-891, and M16-047 will have the opportunity to roll over into the blinded LTE period of M16-047 to continue receiving the same daily dose of upadacitinib for up to Week 524.

Group IV: Placebo / Upadacitinib + Topical Corticosteroids Placebo Group 3 Interventions

Participants will receive placebo orally once a day (QD) for 16 weeks in the double-blind treatment period. At Week 16 participants will be re-randomized to receive either upadacitinib 15 mg or upadacitinib 30 mg QD up to Week 260. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.

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

Published Research Related to This Trial

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 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]

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 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 network meta-analysis of 19 randomized controlled trials involving systemic therapies for moderate-to-severe atopic dermatitis, upadacitinib 30 mg once daily showed the highest efficacy, with 83.6% of patients achieving a significant improvement in eczema severity (EASI-50 response).

Abrocitinib and dupilumab also demonstrated strong efficacy, particularly in combination therapy, but all active treatments had a higher incidence of treatment-emergent adverse events compared to placebo, with no significant differences in safety among the active treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. Silverberg, JI., Thyssen, JP., Fahrbach, K., et al.[2021]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02925117

NCT02925117 | A Study to Evaluate ABT-494 ... The objective of this study was to evaluate the safety and efficacy of multiple doses of upadacitinib monotherapy versus placebo in the treatment of adults ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11116320/

16-Week Results from Phase 3 Clinical Trials (Measure Up ... Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo.

3. news.abbvie.com news.abbvie.com/2024-04-25-New-Data-Show-RINVOQ-R-upadacitinib-Demonstrated-Superiority-Versus-DUPIXENT-R-dupilumab-Across-Primary-and-All-Secondary-Endpoints-in-an-Open-Label-Head-to-Head-Atopic-Dermatitis-Study

New Data Show RINVOQ® (upadacitinib) Demonstrated ... Results from this study show that patients with moderate-to-severe atopic dermatitis can strive for both little to no itch and clearer skin.

4. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2789438

Efficacy and Safety of Upadacitinib in Patients With ... EASI 90/100 indicates 90% or greater/100% improvement in Eczema Area and Severity Index; ITT, intention to treat for the main study; NRS, ...

5. journals.plos.org journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0306463&type=printable

Efficacy and safety of upadacitinib in the treatment of ... The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI). 75% {[Odds Ratio (OR) = ...

6. rinvoqhcp.com rinvoqhcp.com/dermatology/safety

RINVOQ® (upadacitinib) Safety Data RINVOQ is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis

7. rinvoqhcp.com rinvoqhcp.com/safety

RINVOQ® (upadacitinib) Safety Profile Patients treated with RINVOQ are at increased risk for developing infections that may lead to hospitalization or death.

8. jacionline.org jacionline.org/article/S0091-6749(22)01327-6/fulltext

Safety of upadacitinib in moderate-to-severe atopic dermatitis Integrated safety data support the use of both upadacitinib 15 mg and 30 mg doses in patients with moderate-to-severe AD who are candidates ...