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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of dupilumab for individuals with severe, persistent itching due to liver issues. Researchers aim to determine if this treatment can alleviate itchiness associated with certain liver diseases. Individuals who have experienced moderate to severe itching for over six weeks related to liver problems may qualify for this study. Participants will receive an injection of dupilumab every two weeks for 18 weeks. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from an innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that dupilumab has been tested for safety in treating moderate-to-severe atopic dermatitis across various age groups. Studies have found that most patients tolerate dupilumab well. Common side effects include mild reactions at the injection site. However, limited safety information exists for individuals with specific health conditions, such as heart problems or HIV.

Dupilumab's approval for other conditions suggests it is generally safe. This trial is in an early stage, so researchers are still gathering detailed safety information. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about dupilumab for severe chronic itching because it offers a unique approach by targeting the underlying causes of inflammation. Unlike traditional treatments that might focus on symptom relief, dupilumab works by blocking specific proteins involved in the inflammatory response, potentially reducing itching and skin irritation more effectively. This treatment is administered via subcutaneous injection every two weeks, which could be more convenient for patients compared to daily medications. Its targeted action and convenient administration make dupilumab a promising option for those suffering from persistent itching.

What evidence suggests that dupilumab might be an effective treatment for chronic itching?

Research has shown that dupilumab, the treatment under study in this trial, helps reduce severe itching. One study found that 41% of adults using dupilumab experienced a significant decrease in itchiness, compared to only 12% of those receiving a placebo. Another study reported that 83% of patients felt less itchy within four weeks of starting dupilumab. Over time, dupilumab reduced itchiness and related skin problems by nearly 50%. These findings suggest that dupilumab could be a promising option for people with severe chronic itching. ^{6 7 8 9 10}

Who Is on the Research Team?

Jason C Sluzevich

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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]

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 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 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]

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]

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. dupixenthcp.com dupixenthcp.com/atopicdermatitis/efficacy-safety/pruritus-nrs-clinical-trial

Adult Peak Pruritus NRS Efficacy Results 41 % of adults treated with DUPIXENT (n=213) achieved ≥4-point reduction in Peak Pruritus NRS vs 12% with placebo at Week 16 in SOLO 1 (n=212; P<0.001)

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35569006/

Efficacy of dupilumab in chronic prurigo and ... Ninety patients out of 109 (83%) noticed an improvement in pruritus before 4 weeks of dupilumab therapy. At the end of treatment, 18 patients out of 126 (14%) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666328724000683

Dupilumab improves pruritus and skin lesions in patients ... Dupilumab demonstrated efficacy vs placebo in all tested efficacy endpoints, including clinically meaningful reduction in itch, reduction in pruriginous nodule ...

4. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-phase-3-trial-confirms-significant

Dupixent® (dupilumab) Phase 3 Trial Confirms Significant ... Treatment with Dupixent resulted in a nearly 50% reduction in itch and urticaria activity scores from baseline.

5. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2822203

Long-Term Effectiveness and Reasons for Discontinuation ... Responder rates (EASI ≤7 and NRS for pruritus ≤4) varied between 63.6% at week 16 and 78.1% for up to 5 years of treatment, and the median (IQR) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02277769

NCT02277769 | Study of Dupilumab (REGN668/ ... The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults. Am J Clin Dermatol ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9895771/

Dupilumab for the treatment of prurigo nodularis Dupilumab's long-term safety data in patients with systemic diseases like cardiovascular disease, HIV infection and malignancies remain insufficient, and ...

8. dupixenthcp.com dupixenthcp.com/copd/efficacy-safety/safety-data

COPD Clinical Trials Safety Data Avoid use of live vaccines during treatment with DUPIXENT. ADVERSE REACTIONS: Most common adverse reactions are: Atopic Dermatitis (incidence ≥1%): injection ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1314768

Dupilumab Treatment in Adults with Moderate-to-Severe ... Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side- ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02260986

NCT02260986 | Study to Assess the Efficacy and Long- ... Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/​SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis (CHRONOS).