Dupilumab for Asthma

(VIA Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Larry Borish, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Virginia

Must be taking: Albuterol, Inhaled corticosteroids

Must not be taking: Asthma biologics, Antivirals

Disqualifiers: Smoking, COPD, Pregnancy, others

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Often when people with asthma get a virus caused by the common cold (rhinovirus), they also experience an increase or worsening of their asthma symptoms. The purpose of this study is to see if the study medication dupilumab helps prevent those with mild to moderate asthma from having increased asthma symptoms, after being exposed to an experimental rhinovirus inoculation. This is a study about dupilumab which is a drug approved by the U.S. Food and Drug Administration (FDA) for treatment of moderate to severe asthma. Dupilumab is a medication that blocks pathways that cause asthmatic inflammation in the lungs, leading to symptoms and worsening lung function. During this study, subjects will be given either dupilumab or placebo and will subsequently be exposed to the the "common" cold virus (rhinovirus). The virus that the investigators are using has been safely used before in many studies like this involving thousands of volunteers, and the safe use of the virus in this research study has been reviewed by the FDA. The investigators will track asthma symptoms during the study with lung function tests, questionnaires, specimen collection, biomarkers, and physical exams. For data analysis the investigators will assess the samples collected to determine changes in the treatment groups. The investigators will also asses the symptom scores and deviations from baseline measures for lung function.

Do I need to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have used asthma biologic therapy, antiviral, immunosuppressive, or immune modulator therapies in the last 3 months. It also excludes those using inhaled nasal sprays.

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 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, mostly in patients treated for atopic dermatitis. ^{1 2 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 the inflammation process of asthma. This mechanism may offer an advantage over other biologics by being effective in both eosinophilic and non-eosinophilic severe asthma types, unlike some existing treatments. ^{1 2 3 4 7}

Eligibility Criteria

Adults aged 18-40 with mild, well-controlled asthma may join this study. They must have a positive methacholine test, certain blood or breath markers of inflammation, and no recent use of strong immune therapies. Smokers or those with other lung diseases can't participate. Women who can get pregnant must use effective birth control.

Inclusion Criteria

Your blood eosinophil count is 150 or higher, or your FeNO level is 20 or higher.

You have a positive methacholine test with a concentration of 16 milligrams per milliliter or less.

My asthma is managed with albuterol and possibly low to medium dose ICS, without anti-inflammatory meds for sinus issues.

Exclusion Criteria

Members of the clinical site study team and/or his/her immediate family

Pregnant or breastfeeding women

I have had an asthma attack in the last 6 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either dupilumab or placebo and are subsequently exposed to the rhinovirus

2 weeks

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in biomarkers and symptoms

2 weeks

Regular monitoring visits

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Dupilumab (Monoclonal Antibodies)

Trial Overview The VIA Study is testing if dupilumab prevents worsening asthma symptoms in people with mild to moderate asthma when exposed to the common cold virus (rhinovirus). Participants will receive either dupilumab or a placebo before being exposed to the virus, followed by monitoring through tests and questionnaires.

Participant Groups

Group I: Dupilumab Active Control 1 Intervention

The dupilumab dose regimen selected for this study (300 mg q2w after an initial loading dose of 600 mg)

Group II: Placebo Placebo Group 1 Intervention

A harmless substance that looks like the study drug, but which should have no effect. The placebo formulation used in this study contains all the ingredients present in the active drug, except the active ingredient (IL-4α antibody). Therefore, the risk related to this formulation should be no greater than the risk associated to the active drug.

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:

University of Virginia Charlottesville, VA

Who Is Running the Clinical Trial?

University of Virginia Lead Sponsor

Regeneron Pharmaceuticals Industry Sponsor

References

1. 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.

2. 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] Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting.

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

Dupixent, a New Entrant In the Asthma Lists. [2019] Sanofi and Regeneron's Dupixent (dupilumab)-which is already approved for atopic dermatitis-has an FDA action date of October 20 for its asthma indication. It will join Nucala, (mepolizumab), Cinqair (reslizumab), and Fasenra (benralizumab) as a monoclonal antibody approved as a treatment for the type 2 inflammation phenotype in severe asthma.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Characteristics of Patients with Severe Asthma prior to Starting Dupilumab: The ProVENT Study. [2023] Dupilumab is approved for the treatment of severe type 2 (T2) asthma; however, the characteristics of patients receiving dupilumab in routine clinical practice are incompletely understood. This study describes the characteristics of patients with severe asthma before dupilumab treatment in a real-world setting.

5. 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.

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] 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.

7. 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.

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

Dupilumab in the treatment of asthma. [2020] Dupilumab is a fully human monoclonal IgG4 antibody that blocks IL-4 and IL-13 signaling. Its efficacy has been assessed across a range of atopic diseases, due to its ability to inhibit T helper cell 2 (Th2) mediated inflammation. It has already been approved in the USA and Europe for the treatment of atopic dermatitis. Recently, it also gained approval in the USA as add-on treatment for moderate-to-severe asthma in adolescents and adults. Phase II and III randomized controlled trials have demonstrated improvements in asthma exacerbation rates, FEV1, oral glucocorticoid use and a range of patient-reported outcomes, with a favorable safety profile. This article will review the available clinical trial data relating to the efficacy and safety of dupilumab in the management of asthma and related atopic respiratory conditions.