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

33 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall aim of the study is to determine the clinical efficacy and mechanisms of action of anti-IL-4a (dupilumab) as treatment for patients with Aspirin-Exacerbated Respiratory Disease (AERD).

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.

What data supports the effectiveness of the drug Dupilumab for asthma?

Dupilumab has shown effectiveness in treating severe type-2 asthma by targeting specific pathways involved in inflammation, and its efficacy has been demonstrated in clinical trials. It is already used for other conditions like atopic dermatitis and chronic rhinitis, indicating its potential in managing asthma symptoms. ^{1 2 3 4 5}

Is dupilumab safe for treating asthma?

Dupilumab is generally considered safe for treating moderate to severe asthma, with studies showing minimal adverse events compared to a placebo. However, it may cause an increase in blood eosinophils (a type of white blood cell) and has been associated with some ocular (eye-related) adverse events, particularly in patients treated for atopic dermatitis. ^{1 4 6 7 8}

How is the drug Dupilumab unique for treating asthma?

Dupilumab is unique because it targets the IL-4 and IL-13 signaling pathways, which are involved in asthma inflammation, and it may be effective for both eosinophilic and non-eosinophilic severe asthma types, unlike some other treatments that target only one type. ^{1 2 4 5 7}

Research Team

Tanya M Laidlaw, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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, 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]

References

1. Italy 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Characteristics of Patients with Severe Asthma prior to Starting Dupilumab: The ProVENT Study. [2023]

3. Singapore pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Dupilumab for the treatment of asthma. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Dupilumab in the treatment of asthma. [2020]