Measuring the Effect of Dupilumab Treatment on Mucociliary Clearance (MCC) in Subjects With Moderate to Severe Asthma

A Randomized, Placebo-controlled, Parallel Group Study Designed to Assess the Change in Mucociliary Clearance After 12 Weeks of Treatment With Dupilumab in Patients With Moderate to Severe Asthma

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

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: Dupilumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: John Moore; Phone Number: 412-648-6726; Email: mooreja6@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • The University of Pittsburgh Asthma Institute at UPMC
      • Contact: John Moore; Phone Number: 412-648-6726; Email: mooreja6@upmc.edu
      • Contact: Sally Wenzel, MD; Phone Number: 412-647-9955; Email: swenzel@pitt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Moderate - Severe Th2 (Type 2) High asthma, as defined by Forced Expiratory Volume in one second (FEV1) <90% predicted, on medium to high dose inhaled corticosteroids (ICS) with or without a second controller
• Age > 18
• Inhaled steroid doses of 500micrograms (mcg) per day or more (Fluticasone equivalent)
• Reversibility >/= 12% at screening or within the past 2 years, or a positive methacholine challenge test within the past 2 years, or a positive methacholine challenge during screening
• FEV1/Forced Vital Capacity (FVC)<75%
• Blood Eosinophils (EOS) >300 cells per mm3
• Exhaled Nitric Oxide (FeNO) >25 parts per billion (ppb)
• Asthma Control Test (ACT) score <20

Exclusion Criteria:

• Pregnant, nursing, or unwilling to test for pregnancy
• Current smoker or >10 pack year smoking history
• Body Mass Index (BMI)>37
• Respiratory infection in the last 30 days
• Use of antibiotics or oral prednisone in the last 30 days
• Current or previous use of dupilumab
• Current or recent use of anti-IL-5 therapies
• Any other criteria that place the subject at unnecessary risk
• Diagnosis of other lung diseases including Chronic Obstructive Pulmonary Disease (COPD)
• History of non-skin cell cancer in the last 5 years
• Drug or alcohol addiction in the last 5 years
• Any other uncontrolled disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dupilumab; 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.	Drug: Dupilumab; Dupilumab is supplied as a sterile aqueous solution for SC injection at the concentration of 175 mg/mL in glass pre-filled syringe to deliver 200 mg in 1.14mL.
Placebo Comparator: Placebo; 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.	Other: Placebo; Sterile placebo for dupilumab will be provided in identically matched glass pre-filled syringe to deliver 200 mg in 1.14mL, which will match dupilumab 200 mg (1.14mL).; Other Names: Sucrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mucociliary clearance (MCC) rate	MCC is measured using an aerosol-based nuclear imaging technique	Measured at 12 weeks after the start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FEV1% predicted	Assessed using spirometry after bronchodilator administration.	Measured from baseline to 12 weeks after start of treatment
Change in ACT score	Measured via the Asthma Control Test questionnaire. Scores range from 5 (poor control of asthma) to 25 (complete control of asthma).	Measured from baseline to 12 weeks after start of treatment
Change in sputum eosinophils and T2 gene mean	Measured via sputum induction to obtain airway cells and fluid from patients.	Measured from baseline to 12 weeks after start of treatment
Change in mucus plugging score by CT	Radiologists will visually assess the presence or absence of mucus plugging in segmental airways and will provide a mucus plugging score	Measured from baseline to 12 weeks after start of treatment
Whole lung MCC90, AAC90	Measured via mucociliary clearance imaging	Measured from baseline to 12 weeks after start of treatment
Peripheral and central lung MCC90, MCC240, AAC90	Measured via mucociliary clearance imaging	Measured from baseline to 12 weeks after start of treatment

Collaborators and Investigators

• Sponsor: Sally E. Wenzel MD

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: STUDY20020131

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No