Dupilumab for Respiratory Diseases

Overseen By Andrew White, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Scripps Clinic

Must be taking: Dupilumab

Must not be taking: Omalizumab, Tezepelumab, Mepolizumab, others

Disqualifiers: Unstable asthma, Pregnancy, 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: 1

Duration: 6 weeks

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on dupilumab for at least 12 weeks before joining, and you cannot have used other respiratory biologics in the past 3 months.

Is Dupilumab generally safe for humans?

Dupilumab is generally considered safe for humans, with minimal adverse events reported in patients with moderate to severe asthma. However, some ocular (eye-related) adverse reactions have been noted, especially in patients treated for atopic dermatitis. ^{1 2 3 4 5}

What makes the drug Dupilumab unique for treating respiratory diseases?

Dupilumab is unique because it is a monoclonal antibody that targets and blocks the interleukin-4 and interleukin-13 pathways, which are key drivers of type 2 inflammation in conditions like asthma and chronic rhinosinusitis with nasal polyps. Unlike traditional immunosuppressive therapies, Dupilumab does not increase the risk of infections and may even offer protective benefits in certain cases. ^{1 4 6 7 8}

What is the purpose of this trial?

Aspirin-Exacerbated Respiratory Disease (AERD), although uncommon in the general population, is an important phenotype of severe asthma and nasal polyposis where it occurs in 15% of severe asthmatics, and up to 30% of those with nasal polyposis. An important therapy for AERD is aspirin therapy after desensitization (ADAT). This is an inexpensive and proven therapy to improve the burden of sinus disease in AERD. Aspirin desensitization is the mechanism by which tolerance is induced in AERD patients. This is a 1-2 day outpatient procedure whereby increasing doses of aspirin are administered and the patients invariably experience some degree of hypersensitivity reactions. It is important to understand the effect of medications on the aspirin desensitization. It is known that the leukotriene modifier medications decrease the severity of the reactions in AERD. Other treatments such as antihistamines and the biologic agent omalizumab might have an effect on either blocking or blunting reactivity in AERD during desensitization. Dupilumab is a new respiratory biologic approved for atopic dermatitis, eosinophilic asthma and nasal polyposis. As such, it is well situated to be used for many AERD patients whose disease cannot be well controlled. The effect of dupilumab on the aspirin desensitization process and reaction is unknown and is the topic of this investigation. The primary objective is to determine the effect of dupilumab on reactions during aspirin challenge/desensitization.

Eligibility Criteria

This trial is for adults over 18 with Aspirin-Exacerbated Respiratory Disease (AERD), diagnosed through specific tests or a history of reactions to aspirin. Participants must be on dupilumab treatment for at least 12 weeks and have a confirmed history of nasal polyposis.

Inclusion Criteria

I have a confirmed history of nasal polyps.

I have been taking dupilumab for asthma or nasal polyps for at least 12 weeks.

Exclusion Criteria

I cannot take montelukast before treatment.

I haven't used asthma or COPD biologic treatments in the last 3 months.

Unstable asthma or history of severe reactions during previous desensitization attempts

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dupilumab or placebo for 6 weeks before undergoing aspirin challenge

6 weeks

Aspirin Challenge

Participants undergo a standardized aspirin challenge to assess reactions

1-2 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the aspirin challenge

4 weeks

Treatment Details

Interventions

• Dupilumab

Trial Overview The study investigates the effect of dupilumab, a medication approved for certain respiratory conditions, on the process and reactions during aspirin desensitization in AERD patients. This involves observing how well patients tolerate increasing doses of aspirin.

Participant Groups

Group I: Aspirin Challenge Experimental Treatment 1 Intervention

All subjects will undergo a standardized aspirin challenge

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?

Scripps Clinic

Lead Sponsor

Trials

15

Recruited

28,400+

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

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Findings from Research

Patients treated with Dupilumab showed a higher risk of contracting COVID-19, but the infections were generally less severe, suggesting that Dupilumab may have a protective effect against severe disease.

The analysis included data from the WHO global pharmacovigilance database, identifying 109 COVID-19 cases among Dupilumab users, indicating a need for further research to clarify the immunological mechanisms behind these observations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase. Mahroum, N., Damiani, G., Watad, A., 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 study of 46 adult patients with moderate-to-severe atopic dermatitis treated with dupilumab, 34.8% experienced ocular adverse events (OAEs), primarily mild to moderate dry eye disease and superficial punctate keratitis.

Patients with pre-existing conditions such as dry eye disease, eyelid eczema, or high IgE levels were more likely to develop OAEs, suggesting that these factors should be considered before starting dupilumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study. Touhouche, AT., Cassagne, M., Bérard, E., et al.[2021]

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 significantly improves lung function and asthma control in patients with moderate to severe asthma, as evidenced by better forced expiratory volume and asthma control questionnaire scores over 12 and 24 weeks in 13 trials.

The treatment is generally safe, showing no significant increase in adverse events compared to placebo, although it was associated with higher blood eosinophil levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. Zaazouee, MS., Alwarraqi, AG., Mohammed, YA., et al.[2022]

Dupilumab is a monoclonal antibody that targets the IL-4 receptor, blocking signals from IL-4 and IL-13, and is currently in phase III trials for treating moderate-to-severe asthma, showing promise for both eosinophilic and non-eosinophilic asthma phenotypes.

While dupilumab appears to be generally well tolerated, further large-scale studies are necessary to fully evaluate its long-term safety and efficacy, especially in pediatric populations where data is currently lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab for the treatment of asthma. Santini, G., Mores, N., Malerba, M., et al.[2019]

Dupilumab is a monoclonal antibody that effectively targets the IL-4 receptor, significantly improving symptoms and quality of life in adults with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP) over 24 to 52 weeks in phase III studies.

The treatment was well tolerated and led to reductions in nasal polyp size, sinus opacification, and the need for systemic corticosteroids or nasal polyp surgery, showing benefits even in patients with comorbid asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. Hoy, SM.[2022]

Dupilumab significantly improved the quality of life for adolescents with uncontrolled severe asthma within just 4 weeks of treatment, with 80% of participants able to reduce their inhaled corticosteroid dosage.

Throughout the 24-week study, none of the five adolescents experienced asthma exacerbations, indicating that dupilumab effectively controlled their asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time effect of dupilumab to treat severe uncontrolled asthma in adolescents: A pilot study. Indolfi, C., Dinardo, G., Klain, A., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase. [2022]

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

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

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

Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study. [2021]

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

Dupilumab: First Global Approval. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. [2022]

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

Dupilumab for the treatment of asthma. [2019]

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

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Time effect of dupilumab to treat severe uncontrolled asthma in adolescents: A pilot study. [2023]