Upadacitinib for Atopic Dermatitis

(Flex-Up Trial)

No longer recruiting at 236 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: AbbVie

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how flexible dosing of upadacitinib can treat moderate to severe atopic dermatitis, a chronic, itchy skin condition. Upadacitinib, an oral medication already used for other inflammatory diseases, is being evaluated for its effectiveness and safety with adjusted doses. Participants may be divided into groups to receive either 15 mg or 30 mg doses, with their response determining any dose adjustments halfway through the trial. The trial seeks adults who have had atopic dermatitis for at least three years and have not found relief with typical skin treatments. As a Phase 4 trial, it involves an FDA-approved treatment, aiming to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for upadacitinib?

Research has shown that upadacitinib is generally safe and well-tolerated for treating atopic dermatitis (AD). Studies have found that both the 15 mg and 30 mg doses are safe for individuals with moderate to severe AD. Other studies confirm that the safety profile of upadacitinib aligns with previous findings, with no new safety issues identified.

However, individuals taking upadacitinib may face a higher risk of infections, which can sometimes be serious. These findings are based on its use in treating other conditions like rheumatoid arthritis and Crohn's Disease, where the drug has already received approval. It is crucial to discuss the risks and benefits with a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about upadacitinib for atopic dermatitis because it offers a new approach compared to current treatments like topical steroids and calcineurin inhibitors. Upadacitinib is an oral medication that works by inhibiting Janus kinase (JAK), a key player in the inflammation process, potentially offering a more targeted approach to reducing eczema symptoms. Unlike many traditional therapies that focus on surface symptoms, upadacitinib targets the underlying immune responses, which could lead to longer-lasting relief and improved skin health. This new mechanism of action might also result in faster and more significant improvements for patients suffering from this chronic skin condition.

What is the effectiveness track record for upadacitinib in treating atopic dermatitis?

Research has shown that upadacitinib effectively treats moderate to severe atopic dermatitis (AD). Studies found that participants taking upadacitinib experienced less itching and clearer skin compared to those taking a placebo, which contains no active medicine. One study showed that upadacitinib outperformed another treatment, dupilumab, in improving skin condition and reducing itchiness. Participants also reported a better quality of life with fewer symptoms. This trial will evaluate different dosages of upadacitinib, which is already approved for treating AD, to further support its effectiveness for this condition. ^{3 4 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults aged 18-64 with moderate to severe atopic dermatitis (eczema) for over 3 years, who need systemic treatment because skin creams aren't enough or suitable. They should have a certain level of itchiness and affected body area. People can't join if they've had recent serious heart issues, organ transplants, allergies to study drug ingredients, high risk of stomach perforation, absorption problems, certain cancers or infections like HIV/TB/herpes or uncontrolled COVID-19.

Inclusion Criteria

I need systemic treatment for my skin condition because topical treatments aren't effective or suitable for me.

I have had chronic eczema for over 3 years.

I often feel severe itching.

Exclusion Criteria

You have had a stroke, heart attack, or certain surgeries in the last 6 months, or have had an organ transplant and need ongoing medication to suppress your immune system. You have had a severe allergic reaction to the study drug or other similar medications, or have a history of certain gastrointestinal problems. You have conditions that could affect how the drug is absorbed, or have had certain types of cancer.

I have not had multiple severe infections or currently have HIV, active TB, or untreated Hepatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Double-Blind Treatment

Participants are randomized to receive upadacitinib in a double-blind manner for 12 weeks

12 weeks

Regular visits at a hospital or clinic

Single-Blind Treatment

Participants continue treatment with upadacitinib in a single-blind manner for an additional 12 weeks

12 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib

Trial Overview The trial tests the flexibility of dosing Upadacitinib in pill form for adults with eczema. It includes a double-blind period where participants don't know their dose for 12 weeks followed by another 12-week single-blind period with dose adjustments based on response. The goal is to see how well different doses manage eczema symptoms.

How Is the Trial Designed?

Group I: UPA 30 mg Double-Blind Treatment Period --> UPA 30 mg Single-Blind Treatment Period Experimental Treatment 1 Intervention

At Week 12 in the Double-Blind Treatment Period, participants receiving 30 mg upadacitinib orally once daily (QD) achieving a \< 90% reduction in the Eczema Area and Severity Index (EASI) (\< EASI 90) were allocated to receive 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.

Group II: UPA 30 mg Double-Blind Treatment Period --> UPA 15 mg Single-Blind Treatment Period Experimental Treatment 1 Intervention

At Week 12 in the Double-Blind Treatment Period, participants receiving 30 mg upadacitinib orally once daily (QD) achieving a ≥ 90% reduction in the Eczema Area and Severity Index (EASI) (≥ EASI 90) were allocated to receive 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.

Group III: UPA 30 mg Double-Blind Treatment Period Experimental Treatment 1 Intervention

Participants received 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Double-Blind Treatment Period.

Group IV: UPA 15 mg Double-Blind Treatment Period --> UPA 30 mg Single-Blind Treatment Period Experimental Treatment 1 Intervention

At Week 12 in the Double-Blind Treatment Period, participants receiving 15 mg upadacitinib orally once daily (QD) achieving a \< 90% reduction in the Eczema Area and Severity Index (EASI) (\< EASI 90) were allocated to receive 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.

Group V: UPA 15 mg Double-Blind Treatment Period --> UPA 15 mg Single-Blind Treatment Period Experimental Treatment 1 Intervention

At Week 12 in the Double-Blind Treatment Period, participants receiving 15 mg upadacitinib orally once daily (QD) achieving a ≥ 90% reduction in the Eczema Area and Severity Index (EASI) (≥ EASI 90) were allocated to receive 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.

Group VI: UPA 15 mg Double-Blind Treatment Period Experimental Treatment 1 Intervention

Participants received 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Double-Blind Treatment Period.

Upadacitinib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in United States as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

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

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 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]

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 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]

Citations

1. 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.

2. 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 ...

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 ... ... studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown.

5. rinvoqhcp.com rinvoqhcp.com/atopic-dermatitis/efficacy

RINVOQ® (upadacitinib) Efficacy for Atopic Dermatitis The typical RINVOQ patient achieved a 4-point improvement in WP-NRS score from baseline. Data limitations: WP-NRS 0/1 data at Week 16 was a prespecified, non- ...

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 ...