Dupilumab Dosing for Eczema

Overseen By Sumrah Jilani, BS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must be taking: Dupilumab

Must not be taking: Methotrexate, Cyclosporine, others

Disqualifiers: Poor AD control, 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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 16 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking other systemic medications for eczema, you will need to stop them to join this trial. The trial does not specify about other medications, so it's best to discuss with the study team.

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

Dupilumab is a drug that has been approved for treating moderate-to-severe eczema (atopic dermatitis) in adults who do not respond well to topical treatments. It works by blocking certain proteins in the body that cause inflammation, and it has been shown to help reduce symptoms of eczema. ^{1 2 3 4 5}

Is dupilumab safe for treating eczema?

Dupilumab is generally considered safe for treating eczema, but some people may experience side effects like eye problems, local skin infections, increased sweating, and mild reactions at the injection site. ^{3 5 6 7 8}

How is the drug Dupilumab unique for treating eczema?

Dupilumab is unique because it is a monoclonal antibody (a type of protein made in the lab) that targets specific parts of the immune system involved in eczema, specifically the IL-4/IL-13 receptor. It is administered as an injection every two weeks, which is different from many other eczema treatments that are often topical creams or ointments. ^{4 5 9 10 11}

What is the purpose of this trial?

This is a pilot investigator-blinded, randomized clinical trial to assess the feasibility of dupilumab treatment discontinuation or dose-reduction in children aged 1-17 years who have achieved sustained atopic dermatitis (AD) control on dupilumab.

Research Team

Joy Wan, MD MSCE

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for children aged 1-17 with well-controlled atopic dermatitis (eczema) who have been on dupilumab for at least a year. They must understand English and follow study procedures. A parent or guardian's consent (and child's assent if applicable) is required.

Inclusion Criteria

I have been treated with dupilumab for my skin condition for at least a year.

My skin condition has been well-managed with dupilumab in the last 6 months.

I am between 1 and 17 years old.

Exclusion Criteria

I am currently using light therapy for my skin condition.

I do not have health insurance or will lose it during the study.

I am currently on medication for atopic dermatitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either discontinue, reduce, or continue standard dupilumab dosing for atopic dermatitis. This phase includes 5 study visits for skin examination and symptom questionnaires.

16 weeks

5 visits (in-person)

Observational Follow-up

Participants complete questionnaires about AD symptoms and medication use every twelve weeks to monitor long-term effects of treatment changes.

36 weeks

3 follow-up contacts (virtual)

Treatment Details

Interventions

• Dupilumab

Trial Overview The study tests whether it's feasible to stop giving dupilumab or reduce its dose in kids who've had their eczema under control with the standard dose of this medication. It’s a pilot trial where participants are randomly assigned to continue, stop, or reduce the drug.

Participant Groups

Group I: Dupilumab - standard dosing Experimental Treatment 1 Intervention

Participants will continue to receive standard maintenance dupilumab dosing for atopic dermatitis according to FDA labeling, as indicated below. Infants ≥6 months and Children \<6 years: 5 to \<15 kg: 200 mg every 4 weeks. 15 to \<30 kg: 300 mg every 4 weeks Children ≥6 years and Adolescents ≤17 years: 15 to \<30 kg: 300 mg every 4 weeks 30 to \<60 kg: 200 mg every other week ≥60 kg: 300 mg every other week

Group II: Dupilumab - dose reduction Experimental Treatment 1 Intervention

Participants whose standard dupilumab dosing for atopic dermatitis is 200 mg or 300 mg every 2 weeks will decrease drug administration to every 4 weeks, and participants whose standard dupilumab dosing is 200 mg or 300 mg every 4 weeks will decrease administration to every 8 weeks.

Group III: Dupilumab - discontinuation Experimental Treatment 1 Intervention

Participants will discontinue their dupilumab treatment for atopic dermatitis.

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?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

Findings from Research

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]

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, an IL-4 receptor antagonist, is the first FDA-approved biological therapy for moderate-to-severe atopic dermatitis (AD) and has shown improved outcomes in patients inadequately controlled by topical treatments.

However, this case report highlights new side effects, specifically hyperhidrosis and bromhidrosis, in two patients after starting dupilumab, suggesting the need for further research on its long-term safety and potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Something to Sweat About: Two Cases of Dupilumab-Induced Hyperhidrosis and Bromhidrosis. Rowane, M., Valencia, R., Schend, J., et al.[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]

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 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]

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 (Dupixent) has been associated with a risk of ocular adverse reactions, highlighting the importance of monitoring patients for eye-related side effects during treatment.

Prompt management of any ocular issues is essential for patients receiving dupilumab, ensuring their safety and well-being while benefiting from the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

In a phase 3 clinical trial involving 422 adults with moderate to severe atopic dermatitis, dupilumab administered weekly or every 2 weeks effectively maintained treatment response, with minimal change in Eczema Area and Severity Index (EASI) scores compared to placebo.

Longer dosing intervals (every 4 or 8 weeks) led to a significant decrease in treatment efficacy, while no new safety concerns were identified, supporting the recommendation of the approved regimen of 300 mg dupilumab every 2 weeks for long-term management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial. Worm, M., Simpson, EL., Thaçi, D., et al.[2021]

In a study involving 379 adults with moderate-to-severe atopic dermatitis, dupilumab showed a dose-dependent increase in efficacy, particularly at higher doses of 300 mg every 2 weeks or weekly, indicating its effectiveness in reducing symptoms.

The pharmacokinetics of dupilumab were similar between Japanese and non-Japanese patients, suggesting that ethnicity does not significantly affect the drug's behavior in the body, which supports its use across diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, and exposure-efficacy of dupilumab in adults with atopic dermatitis. Kamal, MA., Davis, JD., Kovalenko, P., et al.[2023]

In a study of 295 adult patients with atopic dermatitis treated with dupilumab, serum levels of the drug at 16 weeks showed a wide range but did not correlate with treatment response or adverse effects over the first year.

The findings suggest that individual responses to dupilumab may vary due to differences in the availability of the interleukin-4 receptor, rather than serum drug levels, indicating a need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Serum Dupilumab Levels at 16 Weeks With Treatment Response and Adverse Effects in Patients With Atopic Dermatitis: A Prospective Clinical Cohort Study From the BioDay Registry. Spekhorst, LS., de Graaf, M., Loeff, F., et al.[2023]

References

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

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

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

Dupilumab: First Global Approval. [2022]

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

Something to Sweat About: Two Cases of Dupilumab-Induced Hyperhidrosis and Bromhidrosis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

8. England pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

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

Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial. [2021]

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

Pharmacokinetics, pharmacodynamics, and exposure-efficacy of dupilumab in adults with atopic dermatitis. [2023]

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

Association of Serum Dupilumab Levels at 16 Weeks With Treatment Response and Adverse Effects in Patients With Atopic Dermatitis: A Prospective Clinical Cohort Study From the BioDay Registry. [2023]