Dupilumab for Asthma

Overseen By John Moore

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sally E. Wenzel MD

Must be taking: Inhaled corticosteroids

Must not be taking: Anti-IL-5 therapies, Dupilumab

Disqualifiers: Pregnancy, Smoking, COPD, Cancer, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Single center, randomized, placebo- controlled study to assess change in mucociliary clearance of moderate to severe asthma patients after treatment with dupilumab or placebo.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it does require that you are on medium to high dose inhaled corticosteroids. If you are using antibiotics, oral prednisone, or certain asthma medications like dupilumab or anti-IL-5 therapies, you may need to stop those before joining.

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

Dupilumab has been shown to be effective in treating severe type-2 asthma, as it targets specific pathways involved in inflammation. It has also been used successfully for other conditions like atopic dermatitis and chronic rhinitis, suggesting its potential effectiveness in asthma. ^{1 2 3 4 5}

Is Dupilumab generally safe for treating asthma?

Dupilumab is generally considered safe for treating moderate to severe asthma, with minimal adverse events reported. It has been shown to improve lung function and reduce inflammation, and its safety profile is similar to a placebo in most cases. ^{2 3 6 7 8}

What makes 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 type 2 inflammation, making it effective for severe asthma that is not well-controlled by standard treatments. It is a monoclonal antibody, which means it is a type of protein designed to specifically target and block these pathways, potentially offering benefits for both eosinophilic and non-eosinophilic severe asthma. ^{1 2 3 4 9}

Eligibility Criteria

Adults over 18 with moderate to severe asthma, who are on high doses of inhaled steroids and have specific markers indicating poor lung function (like low FEV1/FVC or high blood eosinophils). They shouldn't be very overweight, have had certain cancers recently, respiratory infections or used specific asthma drugs lately. Smokers and pregnant women are excluded.

Inclusion Criteria

Your exhaled nitric oxide level is higher than 25 parts per billion.

You have more than 300 eosinophils per cubic millimeter of blood.

My lung function improved by 12% or more recently, or I had a positive asthma test.

Exclusion Criteria

I have not had any cancer other than skin cancer in the past 5 years.

I have not had a respiratory infection in the last 30 days.

You have a very high body mass index (BMI).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dupilumab or placebo for 12 weeks, with injections every 2 weeks

12 weeks

1 visit (in-person) for loading dose, subsequent doses administered at home

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dupilumab
• Placebo

Trial Overview The study is testing the effects of Dupilumab versus a placebo on how well the lungs clear mucus in patients with moderate to severe asthma. It's a controlled trial where participants are randomly chosen to receive either Dupilumab or an inactive substance.

Participant Groups

Group I: Dupilumab Active Control 1 Intervention

Two injections of Dupilumab will be administered at Week 0/Visit 3 as a loading dose. Subsequently one injection of Dupilumab will be given every 2 weeks ± 3 days at home by the patient. The doses of investigational product must be separated by ≥11 days to avoid an overdose.

Group II: Placebo Placebo Group 1 Intervention

Two injections of placebo will be administered at Week 0/Visit 3 as a loading dose. Subsequently one injection of placebo will be given every 2 weeks ± 3 days at home by the patient. The doses must be separated by ≥11 day.

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?

Sally E. Wenzel MD

Lead Sponsor

Trials

5

Recruited

800+

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]

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]

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]

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]

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 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, 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]

In a study of 64 patients with severe asthma, dupilumab significantly improved asthma control and lung function after 12 months, as evidenced by a notable increase in asthma control test scores and forced expiratory volume.

Dupilumab also reduced the need for oral steroids and the frequency of asthma exacerbations, although some patients experienced hypereosinophilia, which did not affect the overall clinical response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort. Dupin, C., Belhadi, D., Guilleminault, L., et al.[2021]

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. England pubmed.ncbi.nlm.nih.gov

Dupilumab for the treatment of asthma. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Singapore pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Dupilumab in the treatment of asthma. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort. [2021]