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AsthmaPhase 3NCT03884842

Dupilumab on Airway Hyper-responsiveness and Ventilation Heterogeneity in Patients With Asthma.

A Phase 3 study testing Dupilumab/Dupixent in people with Asthma, run by McMaster University at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In asthmatics with airway hyperresponsiveness and a "T2 immune signature" (type 2), Dupilumab will suppress airway hyperresponsiveness (assessed by methacholine PC20 ≤ 4 mg/mL (PC20: provocative concentration causing a 20% fall in FEV1) OR ≥15% decreased in forced expired volume in 1 second (FEV1) during saline… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Asthma
What is being tested?
Dupilumab/Dupixent
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteCanada
Study dates
1 Jul 2019to 17 Jan 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General
  • Able and willing to provide written informed consent.
  • Able and willing to comply with the study protocol.
  • Males and females ≥ 18 years of age.
  • Asthma-related
  • Asthma diagnosed by a respiratory physician ≥ 12 months prior to study enrolment based on the Global Initiative for Asthma (GINA) 2014 guidelines.
Show all 10Show fewer
  • ACQ > 1 during the screening period.
  • Airway hyperresponsiveness (methacholine PC20 ≤ 4 mg/mL OR ≥15% decreased in FEV1 during saline inhalation for sputum induction OR ≥25% improvement in FEV1 after bronchodilator) during the screening period.
  • Fraction of exhaled nitric oxide (FeNO) >25 ppb and either ≥3% sputum eosinophils (preferred) OR blood eos ≥300/µL during the screening period.
  • Inhaled corticosteroids (ICS) dose ≥500 mcg of fluticasone equivalent/day. Patients on prednisone would not be excluded as long as they meet the rest of the inclusion criteria.

Who cannot join

  • Patients who meet any of the following criteria will be excluded from study entry:
  • Prior Medical Conditions and Treatment History
  • Acute or chronic parasitic, bacterial, fungal or viral infections that required, or currently requires, hospitalization or antimicrobial treatment during the last four weeks.
  • Acute asthma exacerbation event treated with increased doses of oral, or any dose of intramuscular (IM) or intravenous (IV) corticosteroids within six weeks prior to screening.
  • Other relevant pulmonary diseases (e.g. chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension, tuberculosis) requiring treatment within 12 months prior to screening.
  • Alcohol or substance abuse within 12 months prior to screening.
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  • Current smoker defined as having smoked at least one cigarette (or pipe, cigar, or marijuana) per day for ≥ 30 days within the three months prior to screening.
  • Ex-smokers with ≥ 10 pack-year smoking history.
  • Treatment with anti-IgE (immunoglobulin E), anti-IL-4, anti-IL-5 (interleukin-5), or anti-IL-13 targeted therapy currently or within three months prior to screening.
  • ACQ > 3.0
  • MRI (Magnetic Resonance Imaging )Related
  • Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist).
  • In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia.
  • General
  • Participation in any clinical trial of an investigational agent or procedure within six months prior to screening or during the study.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Firestone Institute for Respiratory Health, St. Joseph's Healthcare

    Hamilton, Ontario, L8N 4A6

Other trials in Canada

About this study

Official title: A Two-arm, Placebo-controlled Randomized Clinical Trial to Evaluate the Effect of Dupilumab on Airway Hyper-responsiveness and Ventilation Heterogeneity in Patients With Asthma With a "T2 Immune Signature"

In asthmatics with airway hyperresponsiveness and a "T2 immune signature" (type 2), Dupilumab will suppress airway hyperresponsiveness (assessed by methacholine PC20 ≤ 4 mg/mL (PC20: provocative concentration causing a 20% fall in FEV1) OR ≥15% decreased in forced expired volume in 1 second (FEV1) during saline inhalation for sputum induction OR ≥25% improvement in FEV1 after bronchodilator) and airway eosinophilia (assessed by sputum eosinophils) and this will be associated with greater asthma control and improved ventilation heterogeneity.

Read the detailed description

Along with these features of eosinophil recruitment, degranulation and autoantibody generation, that are partly dependent on (interleukin-4) IL-4 and (interleukin-13) IL-13 signalling, two additional characteristic features of asthma ie airway hyperresponsiveness and mucus hypersecretion are also determined by IL-13 biology. Neither of these important features have been investigated in any clinical trials of anti-IL-13 molecules. Accurate endotyping to identify patients in whom IL-13 mediated biology is the dominant pathobiology of asthma (selecting patients with significant airway hyperresponsiveness and mucus secretion) may elicit greater clinical effect. Taken together, we propose to investigate the effects of Dupilumab on airway hyperresponsiveness, on airway eosinophilia and mucus biology and their relation to airway structure and function (ventilation heterogeneity), and airway autoimmune responses.

To satisfy the proposed objective we will evaluate well-established outcome measures of airway hyperresponsiveness (provocation concentration of methacholine causing a 20% fall in FEV1 (PC20), type 2 inflammation (sputum eosinophils, blood eosinophils and exhaled nitric oxide (eNO)) and mucus biology.

Conditions
Asthma
Being tested
Dupilumab/Dupixent, Placebo
Keywords
Airway hyperresponsivness, Ventilation heterogeneity, Hyperpolarized Xenon-129, Sputum eosinophils
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dupilumab/DupixentBiological

    a monoclonal antibody designed for the treatment asthma and atopic dermatitis.

  • PlaceboBiological

    Matched placebo

Study groups in NCT03884842
Study groupRoleWhat they receive
dupilumabActive comparatorDupilumab 300 mg subcutaneously (SC) every 2 weeks as an investigational drug. For those randomized to dupilumab, a loading dose of 600 mg will be given only at randomization/Visit 2. Sterile dupilumab of will be provided in 150 mg/mL in glass prefilled syringes (2.25 mL total volume) to deliver 300 mg in 2 mL.
Receives: Biological: Dupilumab/Dupixent
matched placeboPlacebo comparatorSterile placebo for dupilumab will be provided in identically matched glass prefilled syringes to deliver 2 mL.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients that achieve at least one doubling dose improvement in PC20 methacholine and/or a 50% reduction in FEV1 reversibility after bronchodilator.

    For patients that can undergo a methacholine challenge, one doubling dose improvement in PC20 methacholine. For those that cannot undergo a methacholine challenge a 50% reduction in FEV1 reversibility.

    Measured: Between screening (week -4) and week 16.

Secondary outcomes (9)

  1. Change in geometric mean PC20 methacholine.

    Change in PC20 between screening and week 16.

    Measured: Between screening (week -4) and week 16.

  2. Change in FEV1 reversibility.

    Change in FEV1 % reversibility (pre/post bronchodilator) between randomization and end of treatment.

    Measured: Between randomization (week 0) and week 16.

  3. Change in sputum eosinophil percentage (%)

    Change in sputum eosinophil percentage between randomization and end of treatment

    Measured: Between randomization (week 0) and week 16.

  4. Change in blood eosinophil count

    Change in blood eosinophil count levels between randomization and end of treatment

    Measured: Between randomization (week 0) and week 16.

  5. Change in fraction of exhaled nitric oxide (FeNO)

    Change in FeNO values parts per billion (ppb) from randomization and end of treatment.

    Measured: Between randomization (week 0) and week 16.

  6. Change in FEV1 (pre-bronchodilator)

    Change in pre-bronchodilator FEV1 values (in litres) between randomization and end of treatment.

    Measured: Between randomization (week 0) and week 16.

  7. Change in Asthma Control Questionnaire-5 (ACQ-5)

    Change in ACQ scores between randomization and end of treatment.

    Measured: Between randomization (week 0) and week 16.

  8. Change in Asthma Control Questionnaire-5 (AQLQ)

    Change in AQLQ scores between randomization and end of treatment.

    Measured: Between randomization (week 0) and week 16.

  9. Change in Asthma Control Test (ACT)

    Change in ACT scores between randomization and end of treatment.

    Measured: Between randomization (week 0) and week 16.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2019
  2. Study start1 Jul 2019
  3. Primary completion12 Oct 2022
  4. Study completion17 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03884842
Sponsor's protocol ID
11963
Status last verified
Jan 2023
First submitted
18 Mar 2019
Last updated
20 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD. Interleukin-13: central mediator of allergic asthma. Science. 1998 Dec 18;282(5397):2258-61. doi: 10.1126/science.282.5397.2258.

    PubMed 9856949

  • Svenningsen S, Kirby M, Starr D, Leary D, Wheatley A, Maksym GN, McCormack DG, Parraga G. Hyperpolarized (3) He and (129) Xe MRI: differences in asthma before bronchodilation. J Magn Reson Imaging. 2013 Dec;38(6):1521-30. doi: 10.1002/jmri.24111. Epub 2013 Apr 15.

    PubMed 23589465

  • Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309-29. doi: 10.1164/ajrccm.161.1.ats11-99. No abstract available.

    PubMed 10619836

  • Svenningsen S, Kjarsgaard M, Haider E, Venegas C, Konyer N, Friedlander Y, Nasir N, Boylan C, Kirby M, Nair P. Effects of Dupilumab on Mucus Plugging and Ventilation Defects in Patients with Moderate-to-Severe Asthma: A Randomized, Double-Blind, Placebo-Controlled Trial. Am J Respir Crit Care Med. 2023 Nov 1;208(9):995-997. doi: 10.1164/rccm.202306-1102LE. No abstract available.

    PubMed 37603097

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dupilumab/Dupixent in people with Asthma, run by McMaster University at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients that achieve at least one doubling dose improvement in PC20 methacholine and/or a 50% reduction in FEV1 reversibility after bronchodilator. (time frame: Between screening (week -4) and week 16.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03884842, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2023.

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Clinical Trial NCT03884842 | AzTrials