Upadacitinib vs Dupilumab for Eczema

(Start Up Trial)

Recruiting at 102 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

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

Disqualifiers: Psoriasis, Lupus, Skin infections, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

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. Topical therapies applied over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study compares upadacitinib to dupilumab in pediatric participants with moderate to severe AD who are candidates for systemic therapy. Adverse events and change in the disease activity will be assessed. Upadacitinib is an approved drug for treating AD patients aged 12 or older. Participants will receive upadacitinib (given as daily dose) or dupilumab (given at label indicated dose every 2 or 4 weeks). Participants will be stratified depending on disease severity, age and response to previous treatment. There is 1 in 5 chance for participants to receive dupilumab during the randomized cohort. Approximately 675 participants aged 2 to less than 12 years of age will be enrolled in this study at approximately 150 sites worldwide. The study population (As defined by participants age or prior treatment) to be enrolled in the study is dependent on local regulatory requirement and/or agreement. Participants will receive upadacitinib oral tablets once daily (or oral solution twice a day) for 160 weeks, or dupilumab as per its label for 52 weeks, and followed for 30 days after the last dose of upadacitinib and at least 12 weeks after the last dose of dupilumab. 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 clinical assessments, blood tests, checking for side effects and completing questionnaires.

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.

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

Dupilumab has been shown to be effective in treating moderate-to-severe atopic dermatitis (eczema) in adults, with studies indicating that it can help achieve a mild level of disease within 4 weeks for some patients. It works by blocking certain proteins in the body that cause inflammation, which is a key factor in eczema. ^{1 2 3 4 5}

Is Dupilumab safe for treating eczema?

Dupilumab is generally considered safe for treating eczema, with a safety profile similar to a placebo. However, some patients may experience side effects like conjunctivitis (eye inflammation), skin infections, or facial redness. ^{3 6 7 8 9}

How do the drugs Upadacitinib and Dupilumab differ in treating eczema?

Upadacitinib and Dupilumab are both used to treat eczema, but they work differently. Upadacitinib is an oral medication that inhibits Janus kinase 1 (a protein involved in inflammation), while Dupilumab is an injectable monoclonal antibody that blocks specific proteins (IL-4 and IL-13) involved in the immune response. Upadacitinib may have a lower risk of causing eye-related side effects compared to Dupilumab. ^{2 5 6 10 11}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

I had a poor response or couldn't tolerate dupilumab and common eczema treatments.

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.

Trial Timeline

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

Treatment Details

Interventions

• Dupilumab (Monoclonal Antibodies)
• Upadacitinib (Other)

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.

Participant Groups

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.

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

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]

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 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 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]

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 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]

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]

References

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

Dupilumab: First Global Approval. [2022]

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

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study. [2023]

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

Dupilumab (Dupixent): An Interleukin-4 Receptor Antagonist for Atopic Dermatitis. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Predictive Factors of Early Response to Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Prevalence of ocular disease during dupilumab treatment for atopic dermatitis: a bicentric retrospective comparative cohort study. [2021]

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

Treatment With Dupilumab in Patients With Atopic Dermatitis: Systematic Review and Meta-Analysis. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Dupilumab leads to an increased chance of head and neck Staphylococcus aureus infection in atopic dermatitis patients. [2023]

8. Germany 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Facial erythema after the treatment of dupilumab in SLE patient. [2022]

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

Ocular Adverse Events in Patients With Atopic Dermatitis Treated With Upadacitinib: A Real-Life Experience. [2023]

11. 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]