Dupilumab for Severe Chronic Itching

Overseen By Rachel A Pung Page

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Opioid antagonists, Corticosteroids

Disqualifiers: Pregnancy, Malignancy, Liver transplant, 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: 11

Duration: 18 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

To investigate the potential efficacy of dupilumab in the treatment of moderate to severe chronic hepatic pruritus.

Do I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are using selective opioid antagonists.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using selective opioid antagonists. It's best to discuss your specific medications with the trial team.

What data supports the idea that Dupilumab for Severe Chronic Itching is an effective drug?

The available research shows that Dupilumab is effective in treating severe chronic itching, particularly in conditions like atopic dermatitis. It works by blocking certain proteins that cause inflammation and itching. Although the research primarily focuses on atopic dermatitis, where itching is a major symptom, it suggests that Dupilumab can significantly reduce itching by targeting the proteins involved in the itch process. This makes it a promising option for those suffering from severe chronic itching. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Dupilumab for severe chronic itching?

Dupilumab is effective in reducing itching because it blocks certain proteins (IL-4 and IL-13) involved in the itching process, and it is already approved for treating atopic dermatitis, a condition where itching is a major symptom. ^{1 2 3 4 5}

What safety data exists for Dupilumab?

Dupilumab, approved for moderate to severe atopic dermatitis, has been associated with several adverse effects. Commonly reported side effects include injection site reactions, conjunctivitis, headache, and nasopharyngitis. Rare effects include alopecia areata and cicatricial ectropion. Facial redness and head and neck dermatitis have been observed in 4-10% of patients, although not initially reported in clinical trials. Ocular adverse reactions are noted, requiring prompt management. Real-world data suggest additional adverse events like blood eosinophilia, rosacea-like skin lesions, and weight gain, but their direct link to dupilumab is unclear. Overall, dupilumab is considered well-tolerated, but long-term safety data and registries are needed to monitor future adverse events. ^{1 6 7 8 9}

Is dupilumab generally safe for humans?

Dupilumab is generally well tolerated, but some people may experience side effects like injection site reactions, conjunctivitis (eye inflammation), headaches, and nasopharyngitis (cold-like symptoms). Rarely, it can cause facial redness or more serious conditions like alopecia areata (hair loss) and cicatricial ectropion (eyelid turning outwards). Long-term safety data is limited, so ongoing monitoring is important. ^{1 6 7 8 9}

Is the drug Dupilumab a promising treatment for severe chronic itching?

Yes, Dupilumab is a promising drug for severe chronic itching. It has shown remarkable effectiveness in reducing itch and improving symptoms in people with atopic dermatitis, a condition that often causes severe itching. ^{1 2 3 10 11}

How is the drug Dupilumab unique for treating severe chronic itching?

Dupilumab is unique because it is a fully human monoclonal antibody that targets the IL-4 and IL-13 signaling pathways, which are involved in allergic reactions, making it effective for conditions like atopic dermatitis. Unlike other treatments, it specifically blocks these pathways, which can help reduce severe itching. ^{1 2 3 10 12}

Research Team

Jason C Sluzevich

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults over 18 with moderate to severe itching due to liver disease lasting more than 6 weeks. Participants must be able to follow the trial procedures and not have a history of certain conditions like liver malignancy, past liver transplants, or specific types of pruritus. Pregnant individuals and those with severe asthma or allergies to dupilumab are excluded.

Inclusion Criteria

Willingness and ability to comply with scheduled clinic visits, physical exams, laboratory tests, questionnaires, and other trial procedures.

I am 18 or older with long-term severe itching due to liver disease.

Documentation of a personally signed and dated informed consent indicating that the subject has been informed of all pertinent aspects of the trial.

Exclusion Criteria

I have itching due to skin inflammation or a psychological condition.

I experience chronic itching due to liver-related cancer.

I have received a liver transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive subcutaneous dupilumab 300 mg every 2 weeks for 18 weeks

18 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Dupilumab

Trial Overview The trial is testing Dupilumab, an injectable medication, for its effectiveness in treating chronic itching associated with liver disease. The goal is to see if this drug can provide relief from persistent and intense itching.

Participant Groups

Group I: Dupilumab Experimental Treatment 1 Intervention

Subcutaneous (SC) dupilumab selected for this study is 300 mg every 2 weeks for 18 weeks.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

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]

Dupilumab, a monoclonal antibody that inhibits the Th2 signaling pathway, is used to treat atopic dermatitis but can lead to the development of psoriasis in some patients, as seen in a case study of a 40-year-old man.

In this case, the abrupt discontinuation of oral steroid therapy alongside dupilumab treatment was identified as potential triggers for the onset of psoriasis, highlighting the need for careful management when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Psoriasis in dupilumab-treated atopic dermatitis]. Senner, S., Eicher, L., Aszodi, N., et al.[2020]

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]

In a case study involving 3 patients with severe itching due to cancer, dupilumab treatment resulted in immediate and complete relief of pruritus after just a few doses, demonstrating its efficacy.

Dupilumab was well-tolerated with no significant adverse effects reported, suggesting it is a safe option for treating intractable malignancy-associated pruritus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab for cancer-associated refractory pruritus. Talmon, A., Elias, S., Rubin, L., et al.[2023]

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]

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]

Dupilumab, a monoclonal antibody approved by the FDA in 2017, effectively treats moderate to severe atopic dermatitis by inhibiting IL-4 and IL-13 signaling, providing an alternative for patients not responding to topical therapies.

While dupilumab is generally effective, it can cause adverse effects such as injection site reactions and conjunctivitis, with rare cases like alopecia areata reported, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab side effect in a patient with atopic dermatitis: a case report study. Albader, SS., Alharbi, AA., Alenezi, RF., et al.[2020]

In a study of 62 adult patients treated with dupilumab for atopic dermatitis, 6% developed head and neck dermatitis, a side effect not previously reported in clinical trials.

The dermatitis typically appeared 8 to 24 weeks after starting treatment and resolved within 8 to 12 weeks, suggesting a potential toxic effect of dupilumab that warrants further investigation into its underlying causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab facial redness: histologic characterization on a series of four cases. Dybała, A., Sernicola, A., Gomes, V., et al.[2022]

Dupilumab is effective and generally well tolerated for treating moderate to severe atopic dermatitis, but patients may experience ocular surface disease more frequently compared to those on placebo.

Real-world data have identified some previously unreported adverse events, such as blood eosinophilia and rosacea-like skin lesions, indicating the need for further long-term studies to clarify their relationship with dupilumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of dupilumab in patients with atopic dermatitis: expert opinion. Francuzik, W., Alexiou, A., Worm, M.[2021]

Dupilumab significantly improved clinical scores for atopic dermatitis (AD) in 175 adults over 48 weeks, reducing both the severity of eczema (measured by EASI) and itch intensity (measured by VAS).

The treatment also led to a decrease in serum biomarkers such as total IgE, LDH, and eosinophil count, indicating its efficacy in managing both symptoms and underlying inflammatory processes associated with AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab Treatment Efficacy and Impact on Clinical Scores, Serum Biomarkers, and Itch in Adult Patients with Atopic Dermatitis: A Retrospective Analysis. Rossi, M., Bettolini, L., Artelli, GL., 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 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]

References

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

Dupilumab: First Global Approval. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

[Psoriasis in dupilumab-treated atopic dermatitis]. [2020]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Dupilumab for cancer-associated refractory pruritus. [2023]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Dupilumab side effect in a patient with atopic dermatitis: a case report study. [2020]

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

Dupilumab facial redness: histologic characterization on a series of four cases. [2022]

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

Safety of dupilumab in patients with atopic dermatitis: expert opinion. [2021]

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

Dupilumab Treatment Efficacy and Impact on Clinical Scores, Serum Biomarkers, and Itch in Adult Patients with Atopic Dermatitis: A Retrospective Analysis. [2023]

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

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

12. England pubmed.ncbi.nlm.nih.gov

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