Upadacitinib vs Dupilumab for Eczema

(Start Up Trial)

Recruiting at 173 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: Corticosteroids, Methotrexate, Cyclosporine, others

Disqualifiers: Psoriasis, Lupus, Skin infections, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 160 weeks for upadacitinib, 52 weeks for dupilumab

675 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two treatments, upadacitinib and dupilumab, to determine which is more effective for children with moderate to severe eczema, a skin condition causing itching and rashes. Researchers aim to assess how these medicines reduce symptoms and identify any side effects. Children who have experienced eczema symptoms for at least six months and find creams or ointments insufficient may be suitable for this trial. Participants will either take upadacitinib as a daily pill or receive dupilumab injections every few weeks. The study will monitor their progress through regular hospital or clinic visits, blood tests, and questionnaires. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking eczema treatments.

Will I have to stop taking my current medications?

Yes, participants must stop certain medications before joining the trial. You cannot use topical treatments for eczema within 7 days before starting, and systemic therapies like corticosteroids or methotrexate must be stopped 4 weeks prior. Dupilumab must be stopped 8 weeks before, and other biologic treatments need to be stopped either 5 half-lives or 12 weeks before, whichever is longer.

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

In earlier studies, upadacitinib has consistently proven to be safe. Research indicates it is well-tolerated by both adults and children aged 12 and older with atopic dermatitis. Recent studies have not reported any new safety concerns. Common side effects include headaches and upper respiratory infections, which are usually mild.

Studies have also shown that dupilumab is safe and effective for treating moderate to severe atopic dermatitis in adults and older children. Participants often experience mild side effects like reactions at the injection site and eye irritation. The data suggest that dupilumab is generally well-tolerated.

Both treatments have been successfully used for atopic dermatitis, but this study will provide more information about their use in younger children. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about upadacitinib for eczema because it works differently from many standard treatments. While traditional options like topical corticosteroids and calcineurin inhibitors primarily focus on reducing inflammation and itching, upadacitinib is a Janus kinase (JAK) inhibitor that targets specific pathways involved in the immune response, potentially offering more precise control over the condition. This targeted approach may lead to improved outcomes for patients who have not responded well to existing therapies. Meanwhile, dupilumab, another treatment under study, is an injectable monoclonal antibody that targets the IL-4 and IL-13 pathways, crucial drivers of inflammation in eczema, offering an alternative for those seeking a different mechanism of action.

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

This trial will compare upadacitinib and dupilumab for treating eczema. Studies have shown that upadacitinib, which participants in this trial may receive, can greatly improve symptoms of atopic dermatitis (AD). Specifically, patients experienced less itching and clearer skin compared to those not receiving the treatment. Research also suggests that upadacitinib provides long-term benefits and remains generally safe over time. Meanwhile, dupilumab, another treatment option in this trial, has effectively reduced AD symptoms in both children and adults, offering significant clinical benefits with a good safety record. Both treatments have successfully managed moderate-to-severe AD, offering hope for better skin and less discomfort. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Children aged 2 to less than 12 with moderate to severe atopic dermatitis (eczema) who haven't responded well to topical treatments or for whom systemic therapy is advised. They must weigh at least 10 kg and meet certain criteria for disease severity, including an EASI score ≥16 and itchiness rating ≥4. Children previously treated with dupilumab without success or those unable to use it due to allergies can join.

Inclusion Criteria

My worst daily itch is rated 4 or higher on a scale.

vIGA-AD score ≥ 3

Participant must satisfy at least one of the specified criteria

Exclusion Criteria

I haven't had skin diseases needing serious treatment in the last month.

I haven't used any skin treatments for AD in the last week.

I have a history of serious eye problems or surgeries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive upadacitinib daily or dupilumab every 2 or 4 weeks, depending on the cohort

160 weeks for upadacitinib, 52 weeks for dupilumab

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after upadacitinib, at least 12 weeks after dupilumab

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab
• Upadacitinib

Trial Overview The trial compares oral upadacitinib taken daily against subcutaneous dupilumab injections every few weeks in children with eczema. It aims to assess side effects and how the disease responds over time, involving regular hospital visits, clinical assessments, blood tests, and questionnaires.

How Is the Trial Designed?

Group I: Randomized Cohort Experimental Treatment 2 Interventions

Participants in the Randomized Cohort will be randomized to receive either medium dose upadacitinib daily adult equivalent dose, low dose upadacitinib daily adult equivalent dose or dupilumab every 2 weeks or 4 weeks (at the label-indicated dose and frequency).

Group II: Dupi-IR Cohort Experimental Treatment 1 Intervention

Participants in this cohort will receive upadacitinib medium dose.

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

Approved in United States as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Approved in European Union as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

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 64 complex patients with moderate-to-severe atopic dermatitis, including the elderly and those on immunosuppressive therapies, 87.5% showed improvement or disease clearance with dupilumab, indicating its efficacy in challenging populations.

While 20.3% of patients experienced side effects, including conjunctivitis and anaphylactic reactions, only 9.4% discontinued treatment due to these effects, suggesting that dupilumab can be safely used in patients with significant co-morbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of use, efficacy, and safety of dupilumab in complex patients: a retrospective, case-series study from a large, urban academic center. Lukac, D., Pagani, K., McGee, JS.[2023]

Dupilumab, a treatment for atopic dermatitis, effectively improved skin lesions in a patient but also caused unexpected facial erythema and desquamation, highlighting potential adverse effects.

The case suggests that while dupilumab is beneficial for atopic dermatitis, it may trigger or exacerbate conditions like systemic lupus erythematosus (SLE), indicating the need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial erythema after the treatment of dupilumab in SLE patient. Jang, DH., Lee, JI., Bae, JY., et al.[2022]

Dupilumab is a monoclonal antibody that targets the IL-4 receptor, effectively inhibiting the action of IL-4 and IL-13, which are key players in allergic diseases.

It received its first approval in March 2017 for treating moderate-to-severe atopic dermatitis in adults who do not respond well to topical treatments, and is also being developed for asthma, nasal polyps, and eosinophilic esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: First Global Approval. Shirley, M.[2022]

Dupilumab is an effective treatment for atopic dermatitis, showing significant improvements in skin symptoms and overall disease control in clinical trials.

The medication works by inhibiting specific pathways in the immune system, which helps reduce inflammation and alleviate the symptoms of atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab (Dupixent): An Interleukin-4 Receptor Antagonist for Atopic Dermatitis. D'Ippolito, D., Pisano, M.[2020]

In a study of 33 adult patients with moderate-to-severe atopic dermatitis who switched from dupilumab to upadacitinib, all patients with dupilumab-associated conjunctivitis experienced complete resolution of their ocular symptoms within one month.

Only 3% of patients developed conjunctivitis after starting upadacitinib, indicating it has a lower incidence of this side effect compared to dupilumab, making it a safer option for patients with ocular symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Adverse Events in Patients With Atopic Dermatitis Treated With Upadacitinib: A Real-Life Experience. Gelato, F., Mastorino, L., Quaglino, P., 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 818 adults with moderate-to-severe atopic dermatitis treated with dupilumab for at least 16 weeks, 12% of patients successfully spaced their doses or withdrew treatment while still maintaining effectiveness.

Key predictors for successful dose spacing or treatment withdrawal included having non-cutaneous atopic manifestations, a prurigo nodularis phenotype, and being older at the start of treatment, suggesting specific patient profiles can benefit from adjusted treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study. Chiricozzi, A., Dal Bello, G., Gori, N., et al.[2023]

Dupilumab significantly improved symptoms of atopic dermatitis (AD) in both adults (n=3,817) and children/adolescents (n=618), showing a marked reduction in the Eczema Area Severity Index (EASI) score and pruritus, indicating its efficacy as a treatment option.

The safety profile of dupilumab was comparable to that of a placebo, with no increase in adverse events, suggesting it is a safe option for managing AD-related symptoms and improving patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment With Dupilumab in Patients With Atopic Dermatitis: Systematic Review and Meta-Analysis. Koskeridis, F., Evangelou, E., Ntzani, EE., et al.[2022]

Dupilumab is the first biological medication approved for treating moderate-to-severe atopic dermatitis, demonstrating significant effectiveness and a favorable safety profile.

Despite its overall safety, there have been rare cases of local Staphylococcus aureus infections reported in patients undergoing dupilumab treatment for atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Dupilumab leads to an increased chance of head and neck Staphylococcus aureus infection in atopic dermatitis patients. Chen, M., Gao, K., Ali, K., et al.[2023]

In a study of 492 patients with moderate-to-severe atopic dermatitis, certain baseline factors, such as having classic or generalized lichenoid inflammatory phenotypes, were found to significantly predict a positive response to dupilumab treatment within 4 weeks.

Patients with a lower baseline Eczema Area and Severity Index (EASI) score also had a higher likelihood of achieving a mild level of disease, emphasizing the importance of early intervention with dupilumab for effective management of atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Factors of Early Response to Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis. Ferrucci, S., Casazza, G., Zussino, M., et al.[2023]

In a study of 100 patients with atopic dermatitis, 36% of those treated with dupilumab developed ocular diseases, significantly higher than the 10% in the reference group.

Severe allergic conjunctivitis and blepharitis were notably more common in the dupilumab group, with 30% and 22% of patients affected, respectively, indicating a need for careful monitoring and potential ophthalmologist consultation before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of ocular disease during dupilumab treatment for atopic dermatitis: a bicentric retrospective comparative cohort study. Barbé, J., Poreaux, C., Remen, T., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38743155/

Dupilumab Safety and Efficacy up to 1 Year in Children ... Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02260986

NCT02260986 | Study to Assess the Efficacy and Long- ... The primary objective of the study was to demonstrate the efficacy of Dupilumab administered concomitantly with topical corticosteroid (TCS) through Week 16 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02277769

NCT02277769 | Study of Dupilumab (REGN668/ ... This is a randomized, double-blind, placebo-controlled, parallel-group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761055Orig1s040.pdf

761055Orig1s040 | FDA Since Dupixent (dupilumab) was approved on March 28, 2017, we have become aware of reports of arthralgia in clinical trials conducted in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9142443/

Long-Term Efficacy and Safety of Dupilumab in Adolescents ... 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/761055Orig1s000PharmR.pdf

761055Orig1s000 - accessdata.fda.gov A Carcinogenicity Risk Assessment for Dupilumab (REGN668/ SAR231893) ... The sponsor believes that its downregulation may prevent or reverse the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02277769

NCT02277769 | Study of Dupilumab (REGN668 ... This is a randomized, double-blind, placebo-controlled, parallel-group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate ...

8. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy00000019m2EAA/nct01639040

Study to Assess the Safety of Dupilumab (REGN668 ... The purpose of this study was to assess the safety of Dupilumab administered concomitantly with topical corticosteroids (TCS) in patients with moderate-to- ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7286262/

Assessing the risk of dupilumab use for atopic dermatitis ... ... (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic ... dupilumab treatment based on the safety data from phase III clinical trials.

10. go.drugbank.com go.drugbank.com/drugs/DB12159/clinical_trials?conditions=DBCOND0019942&phase=1&purpose=treatment&status=completed

Dupilumab Completed Phase 1 Trials for Dermatitis ... Sequential Ascending Dose Study to Assess the Safety and Tolerability of REGN668 (SAR231893) in Patients With Atopic Dermatitis. Dupilumab (DB12159) ...