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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of dupilumab (a monoclonal antibody treatment) during the aspirin desensitization process for individuals with Aspirin-Exacerbated Respiratory Disease (AERD). AERD is a type of asthma where aspirin can trigger breathing problems and sinus issues. Researchers aim to determine if dupilumab can help manage reactions during aspirin desensitization, a process designed to increase aspirin tolerance. Candidates may be suitable if they have AERD, are already using dupilumab for asthma or nasal polyposis, and have a history of nasal polyps. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that dupilumab is likely to be safe for humans?

Previous studies have shown dupilumab to be safe for treating conditions like asthma and nasal polyps. Research indicates it improves breathing and reduces inflammation with few side effects. Most patients experience only mild side effects, and serious ones are rare. This makes dupilumab a promising option for those considering it for Aspirin-Exacerbated Respiratory Disease (AERD). Its approval for other conditions supports its safety for new uses. However, its effect on aspirin desensitization in AERD remains under study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AERD?

Unlike the standard treatments for respiratory diseases, which often involve inhalers or corticosteroids to manage symptoms, Dupilumab offers a unique approach by targeting and inhibiting the activity of specific proteins involved in inflammatory pathways, particularly interleukin-4 and interleukin-13. This targeted action can potentially reduce inflammation more effectively and with fewer side effects. Researchers are excited about Dupilumab because it may provide more sustainable relief and improved quality of life for patients with chronic respiratory conditions by addressing the underlying cause rather than just alleviating symptoms.

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

Research shows that dupilumab effectively treats conditions like severe asthma and nasal polyps, linked to Aspirin-Exacerbated Respiratory Disease (AERD). Studies have found that dupilumab improves breathing and reduces inflammation in patients with chronic sinusitis and nasal polyps, often associated with poorly controlled asthma. It has decreased severe asthma attacks and enhanced lung function. Dupilumab also reduces or eliminates the need for oral steroids, commonly used to manage asthma. In this trial, participants will undergo a standardized aspirin challenge to further explore its effects. While researchers continue to study dupilumab's direct effect on aspirin desensitization in AERD, its benefits in related conditions are promising. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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 (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 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 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]

Citations

1. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-demonstrated-superiority-over-xolairr

Dupixent® (dupilumab) Demonstrated Superiority Over ... New late-breaking data at EAACI showed Dupixent outperformed Xolair across all primary and secondary efficacy endpoints of CRSwNP and in all ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38972450/

Efficacy of dupilumab for severe chronic rhinosinusitis with ... Conclusion: Dupilumab improved upper and lower airway outcomes especially in patients with severe CRSwNP with comorbid, poorly controlled asthma. Trial ...

3. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/latest-dupixentr-dupilumab-and-itepekimab-data-ers-highlight

Latest Dupixent® (dupilumab) and Itepekimab Data at ERS ... Two poster presentations will show new data on the 4-week impact of Dupixent treatment on airway inflammation, volume, and flow, and mucus plugging, as well as ...

4. sanofi.com sanofi.com/en/media-room/press-releases/2022/2022-08-30-05-00-00-2506339

Media Update: New Dupixent® (dupilumab) data at ERS ... New Dupixent® (dupilumab) data at ERS adds to body of safety and efficacy data in chronic respiratory diseases. Paris, August 30, 2022.

5. dupixenthcp.com dupixenthcp.com/asthma/efficacy

Efficacy and Safety Overview DUPIXENT reduced severe exacerbations, improved lung function, reduced or eliminated OCS use, and has a demonstrated safety profile.

6. dupixenthcp.com dupixenthcp.com/asthma/efficacy/safety-data

Safety Data For Asthma | DUPIXENT® (dupilumab) DUPIXENT can be used with or without topical corticosteroids. Chronic Rhinosinusitis with Nasal Polyps: DUPIXENT is indicated as an add-on maintenance ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9574251/

Dupilumab efficacy and safety in patients with moderate to ... Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients ...

8. dupixenthcp.com dupixenthcp.com/crswnp/efficacy/safety-data-and-design

safety data and study designs in adults Review DUPIXENT® (dupilumab) demonstrated safety profile and clinical trial information for inadequately controlled chronic rhinosinusitis with nasal polyps ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02912468

NCT02912468 | A Controlled Clinical Study of Dupilumab ... Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304048

Dupilumab in Persistent Asthma with Elevated Eosinophil ... The objective of this study was to assess the efficacy and safety of dupilumab in adults with persistent, moderate-to-severe asthma and elevated eosinophil ...