Dupilumab for Asthma

(MARINER Trial)

Overseen By Tanya M Laidlaw, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Intranasal steroids

Must not be taking: Biologics, Zileuton, High-dose aspirin

Disqualifiers: Pregnancy, Recent sinonasal surgery, 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: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dupilumab, a medication, to determine its effectiveness for individuals with Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) and Aspirin-Exacerbated Respiratory Disease (AERD), a condition where aspirin triggers breathing problems. The goal is to assess dupilumab's efficacy and its effects on the body. Individuals with doctor-diagnosed asthma, nasal polyps, and reactions to aspirin or similar medicines might be suitable candidates for this trial. Participants should not be current smokers and must have stable asthma, meaning no recent hospital visits or steroid treatments for asthma. As a Phase 2 trial, this research measures dupilumab's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as investigational drugs, biologic agents, systemic glucocorticoids, zileuton, and high-dose aspirin before joining. If you're on these, you may need to stop them for a specific time before the trial.

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

Research has shown that dupilumab is generally well-tolerated. Common side effects include colds and reactions at the injection site, occurring more frequently than in those receiving a placebo (a harmless, inactive substance used for comparison). The FDA has already approved dupilumab for other conditions, suggesting it is considered safe. However, potential participants should be aware of these possible side effects when considering joining a clinical trial. ^{1 2 3 4 5}

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

Unlike the standard asthma treatments that often focus on reducing inflammation or relaxing airway muscles, Dupilumab targets a specific protein called IL-4 receptor alpha. This action blocks the signaling pathways involved in the inflammatory response, which is a key player in asthma symptoms. Researchers are excited about Dupilumab because it offers a novel approach by directly interfering with the immune system's triggers for asthma, potentially leading to better control of symptoms and fewer asthma attacks. Additionally, Dupilumab is administered every other week, which could be more convenient compared to daily medication regimens.

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

Research has shown that dupilumab, the treatment under study in this trial, helps reduce asthma symptoms. One study found it lowered the risk of asthma flare-ups by 44%. Another study revealed that 75% of patients using dupilumab had better asthma control compared to 67% of those taking a placebo. Dupilumab also reduced the need for oral corticosteroids, commonly used to treat severe asthma. These findings suggest that dupilumab can significantly help manage asthma by preventing flare-ups and improving daily symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Tanya M Laidlaw, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults with Aspirin-Exacerbated Respiratory Disease (AERD), featuring asthma, nasal polyps, and reactions to aspirin. Participants must have a BMI over 18, stable asthma without recent severe episodes, visible nasal polyps, impaired sense of smell, and be non-smokers. They should use birth control and not be on certain medications or pregnant.

Inclusion Criteria

I have been using a nasal spray steroid every day for the last 4 weeks.

For females: Practicing FDA-approved methods of birth control for the duration of the study. Female participants of childbearing potential must have a negative pregnancy test upon study entry

History of AERD, defined as meeting the diagnostic triad with: history of physician-diagnosed asthma, history of physician-diagnosed nasal polyposis, and history of pathognomonic reactions to aspirin or other nonselective COX inhibitors

Exclusion Criteria

I have not had sinus surgery in the last 4 months.

Use of investigational drugs within 12 weeks of Screening

I haven't taken any steroid pills or injections in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dupilumab (300mg every-other-week for 8 weeks) with clinical assessments and biospecimen collections at Baseline, Week 2, and Week 8

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab

Trial Overview

The study tests Dupilumab's effectiveness against AERD by comparing it with a placebo. Dupilumab targets the IL4RA protein involved in inflammation. Patients are randomly assigned to receive either Dupilumab or an inactive substance to see if there's a difference in their respiratory symptoms.

How Is the Trial Designed?

Group I: Dupilumab Experimental Treatment 1 Intervention

Subjects will receive dupilumab (300mg every-other-week for 8 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?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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]

Dupixent (dupilumab) is set to receive FDA approval for asthma treatment on October 20, expanding its use beyond atopic dermatitis.

Once approved, Dupixent will be part of a group of monoclonal antibodies, including Nucala, Cinqair, and Fasenra, that target type 2 inflammation in severe asthma, highlighting its role in managing this specific asthma phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupixent, a New Entrant In the Asthma Lists. Reinke, T.[2019]

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]

In a real-life study of 12 patients with severe type-2 asthma, dupilumab treatment for 3 months led to significant improvements in asthma control (ACT score) and lung function (FEV1), indicating its efficacy in managing symptoms.

The treatment also resulted in a notable reduction in FeNO levels, a biomarker for type-2 inflammation, although blood eosinophil counts did not show significant change, suggesting that dupilumab effectively targets the IL4/IL13 pathway in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. Carpagnano, GE., Scioscia, G., Buonamico, E., et al.[2022]

In a study of 99 patients with severe asthma, the majority exhibited diverse clinical characteristics, with 58% having adult-onset asthma and 48% showing an allergic phenotype, indicating a range of profiles among those eligible for dupilumab treatment.

The analysis revealed that 70% of patients met at least one GINA criterion for type 2 airway inflammation, and 64% had comorbidities associated with type 2 inflammation, highlighting the complexity of managing severe asthma in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Characteristics of Patients with Severe Asthma prior to Starting Dupilumab: The ProVENT Study. Korn, S., Schmidt, O., Timmermann, H., et al.[2023]

Dupilumab, a monoclonal antibody that blocks IL-4 and IL-13 signaling, has been shown to significantly improve asthma symptoms and reduce exacerbation rates in adolescents and adults, based on Phase II and III clinical trials.

The treatment has a favorable safety profile and has also been approved for use in atopic dermatitis, highlighting its effectiveness across multiple atopic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab in the treatment of asthma. Grey, A., Katelaris, CH.[2020]

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]

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