Upadacitinib + Topical Corticosteroids for Eczema

(AD Up Trial)

Recruiting at 196 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

1500 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to assess the efficacy and safety of upadacitinib combined with topical corticosteroids (TCS) for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

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.

What data supports the effectiveness of the drug Upadacitinib combined with topical corticosteroids for eczema?

Research shows that Upadacitinib, when combined with topical corticosteroids, is effective for treating moderate-to-severe eczema (atopic dermatitis). Clinical trials have demonstrated a positive benefit-risk profile, meaning the benefits of the treatment outweigh the risks, and it has been shown to work well in both controlled studies and real-life settings. ^{1 2 3 4 5}

Is the combination of Upadacitinib and Topical Corticosteroids safe for treating eczema?

Upadacitinib combined with topical corticosteroids has been shown to have a positive safety profile in treating moderate-to-severe eczema, although some patients may experience side effects like herpes zoster (a type of viral infection) and acne. In clinical trials, the likelihood of side effects was higher with active treatments compared to placebo, but no significant differences were found among the active treatments themselves. ^{1 3 6 7 8}

How is the drug upadacitinib combined with topical corticosteroids unique for treating eczema?

Upadacitinib is an oral medication that works by inhibiting Janus kinase 1 (JAK1), which is different from many other eczema treatments that are applied directly to the skin. When combined with topical corticosteroids, it offers a new approach for managing moderate-to-severe eczema, especially for patients who have not responded well to other systemic therapies. ^{1 2 3 6 9}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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-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]

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 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 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]

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]

References

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

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

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

Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. [2022]

3. 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]

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

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

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

Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies. [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. England pubmed.ncbi.nlm.nih.gov

Background factors predicting the occurrence of herpes zoster in atopic dermatitis patients treated with upadacitinib. [2023]

8. England 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. [2021]

9. 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]