Dupilumab for Respiratory Diseases

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Scripps Clinic

Must be taking: Dupilumab

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

Disqualifiers: Unstable asthma, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

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.

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.

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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.

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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.

I am over 18 and have been diagnosed with a condition worsened by aspirin, confirmed by a test or at least two reactions.

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

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Scripps Clini San Diego, CA

Who Is Running the Clinical Trial?

Scripps Clinic Lead Sponsor

Regeneron Pharmaceuticals Industry Sponsor

University of California, San Diego Collaborator

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] Dupilumab (Dupixent®) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biologic therapy is traditionally regarded as immunosuppressive and capable to increase the infectious risk, Dupilumab does not display these characteristics and may be even protective in certain cases. We investigated the link between Dupilumab therapy and SARS-CoV-2 infection.

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

Safety update: dupilumab and ocular adverse reactions. [2022] Overview of: Medicines and Healthcare products Regulatory Agency. Dupilumab (Dupixent▼): risk of ocular adverse reactions and need for prompt management. Drug Safety Update 2022;16(4): 1.

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

Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study. [2021] Dupilumab is approved for use in moderate-to-severe atopic dermatitis (AD) and as an add-on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD.

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

Dupilumab: First Global Approval. [2022] Dupilumab (Dupixent®) is a fully human monoclonal antibody directed against the interleukin (IL)-4 receptor α (IL-4Rα) subunit. Dupilumab inhibits the signalling of the type 2 cytokines IL-4 and IL-13 and was co-developed by Regeneron Pharmaceuticals and Sanofi as a potential therapeutic agent for the treatment of atopic or allergic diseases. In March 2017 dupilumab received its first global approval, in the USA, for use in the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupilumab is in preregistration for this indication in the EU. In addition, dupilumab is currently under phase III development across the world for the treatment of asthma and nasal polyposis as well as for atopic dermatitis in paediatric patients. The agent has also entered phase II development in the USA for the treatment of eosinophilic oesophagitis. This article summarizes the milestones in the development of dupilumab leading to this first approval for the treatment of moderate-to-severe atopic dermatitis in adults.

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] Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma. Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4. Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events. Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.

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

Dupilumab for the treatment of asthma. [2019] Dupilumab (REGN668/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma. Dupilumab is directed against the α-subunit of the interleukin (IL)-4 receptor and blocks the IL-4 and IL-13 signal transduction. Areas covered: Pathophysiological role of IL-4 and IL-13 in asthma; mechanism of action of dupilumab; pharmacology of IL-4 receptor; phase I and phase II studies with dupilumab; regulatory affairs. Expert opinion: Patients with severe asthma who are not sufficiently controlled with standard-of-care represent the target asthma population for dupilumab. If confirmed, efficacy of dupilumab in both eosinophilic and non-eosinophilic severe asthma phenotype might represent an advantage over approved biologics for asthma, including omalizumab, mepolizumab, and reslizumab. Head-to-head studies to compare dupilumab versus other biologics with different mechanism of action are required. Pediatric studies with dupilumab are currently lacking and should be undertaken to assess efficacy and safety of this drug in children with severe asthma. The lack of preclinical data and published results of the completed four phase I studies precludes a complete assessment of the pharmacological profile of dupilumab. Dupilumab seems to be generally well tolerated, but large studies are required to establish its long-term safety and tolerability.

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

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. [2022] Dupilumab (Dupixent®) is a fully human IgG4 monoclonal antibody against the interleukin (IL)-4 receptor α (IL-4Rα) subunit, which is shared by the type I IL-4 and the type II IL-4/IL-13 receptor complexes. By binding to and blocking this subunit, dupilumab inhibits IL-4 and IL-13, which are the major drivers of human type 2 inflammatory disease [e.g. asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyps (CRSwNP)]. Dupilumab, administered subcutaneously, is the first biological therapy to be approved for the treatment of adults with inadequately controlled CRSwNP in the EU and the USA. In two placebo-controlled, multinational, phase III studies of 24 and 52 weeks' duration, the addition of dupilumab (300 mg every 2 weeks) to the intranasal corticosteroid treatment of adults with severe, inadequately controlled CRSwNP was generally well tolerated and improved nasal polyp size, sinus opacification and health-related quality of life (HR-QOL), relieved the major symptoms of CRSwNP (nasal congestion or obstruction, nasal discharge and loss of smell) and reduced the use of systemic corticosteroids and the need for nasal polyp surgery. Improvements in nasal polyp size, sinus opacification and nasal congestion or obstruction were achieved regardless of the presence of comorbid asthma or NSAID-exacerbated respiratory disease, or a history of previous nasal polyp surgery, with patients with comorbid asthma also demonstrating improvements in lung function and asthma control regardless of their baseline eosinophil count. Thus, add-on subcutaneous dupilumab is a valuable treatment option for adults with inadequately controlled CRSwNP.

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

Time effect of dupilumab to treat severe uncontrolled asthma in adolescents: A pilot study. [2023] Dupilumab is a new biological drug approved for the treatment of type 2 inflammatory diseases, such as asthma. Dupilumab is a fully humanized monoclonal antibody that acts against both interleukin-4 and interleukin-13 receptors. This study evaluated the time--dependent effect of dupilumab on asthma exacerbations and quality of life in adolescents with uncontrolled severe asthma.