Poor Response to Monoclonal Therapy in Asthma (PROCLAIM)

Investigating Poor Response to Monoclonal Therapy in Asthma

Asthma affects 8% of the entire population. 4-5% of asthma sufferers have severe asthma, characterised by recurrent exacerbations (worsening of symptoms leading to the person having a bout of corticosteroids and/or antibiotics), significant symptoms and lack of response to the most widely used therapy, corticosteroids.

There is now new types of treatments (antibody drugs) which are licensed to manage severe asthma such as Anti-IL5. There is evidence Anti-IL5 and other similar antibody drugs are effective at reducing asthma exacerbations and reduce the need for oral corticosteroids for those that have severe asthma.

However, some patients respond poorly to Anti-IL5 and the investigators would like to find out why this happens. It is hoped that the investigators can identify the mechanism of poor treatment response to Anti-IL5. It is also hoped that the investigators can understand why symptoms worsen to the point of requiring antibiotics and/or steroids (also known as an exacerbation) for those prescribed Anti-IL5.

Study Overview

• Status: Unknown
• Conditions: Asthma
• Intervention / Treatment: Drug: Anti-IL5 Antibody; Procedure: Bronchoscopy

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG51PB
    • Recruiting
    • Nottingham Respiratory BRU
    • Contact: Yik L Pang, BMedSci, MBBS, MRCP; Phone Number: 01158231702; Email: mszyp@exmail.nottingham.ac.uk
    • Contact: Mohammad R Ali, BSc, MRes; Phone Number: 0115 82 31339; Email: mohammad.ali@nottingham.ac.uk
    • Principal Investigator: Dominick Shaw, MBBS, FRCS, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the severe asthma clinic. Once the multidisciplinary team (MDT) have decided that the patient will be prescribed anti-IL5 therapy a patient information sheet (PIS) will be posted out by the clinical team. If the appointment with the clinical team is within days of the MDT, potential participant will be approached by a member of the research team and the study will be discussed and a patient information sheet will be given to the patient.

Control participants will be recruited from our Respiratory Research Database and have agreed to be contacted for research. A poster will be created to be put up in Nottingham City Hospital, Queen's Medical Centre and at the University of Nottingham, UK.

Description

Inclusion criteria: case participants:

• Aged 18 - 80 years old
• Able to give informed consent
• All patients identified as being suitable for anti-IL5 therapy by the asthma MDT will be considered for study enrolment.

This assessment by the MDT for participants to be eligible includes:

• A measure of compliance with current asthma medication,
• Confirmation of asthma diagnosis
• Suitability for anti-IL5 therapy based on blood eosinophil counts,
• Asthma exacerbation rates
• Prednisolone dose.
• Confirmation of treatment requires at least two asthma specialists to agree that this is the correct course of action
• Patients must first demonstrate over 75% compliance with inhaled and/or oral corticosteroid therapy

The asthma MDT and difficult asthma clinic normally assess patients between 18-80 years so only patients in this age range will be approached.

All patients will be able to give informed consent for study participation.

Exclusion criteria: case participants:

• Pregnancy

Inclusion criteria: control participants:

• Aged between 18-80 years old.
• Able to give informed consent

Exclusion criteria: control participants:

• Pregnancy
• Underlying respiratory conditions

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe asthma; Untreated by anti-IL5 treatment for severe asthma at point of recruitment. To be prescribed anti-IL5 as part of their treatment following consent. Note: Anti-IL5 treatment is prescribed as per agreed multidisciplinary team meeting, outside of the decision to enrol the patient on the study, and is administered by the clinical team as part of the patient's clinical care outside of the research study.	Drug: Anti-IL5 Antibody; Asthma group: Anti-IL5 treatment Control group: No biologic.; Procedure: Bronchoscopy; Optional for both arms
Healthy control; Control group without respiratory condition	Procedure: Bronchoscopy; Optional for both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of mechanisms associated with poor response to anti-IL5 therapy	Identification of mechanisms associated with poor response to anti-IL5 therapy. A poor response is defined as an inability to halve the pre-treatment annualised exacerbation rate; an asthma exacerbation is defined as a worsening of asthma symptoms necessitating a short burst of oral corticosteroids, or a doubling of maintenance oral corticosteroid treatment dose.	12 months
An improvement in FEV1 as assessed by spirometry	Treatment response as assessed as a clinically meaningful improvement in asthma control (ACQ change of >0.5).	12 months
A clinically meaningful improvement in asthma control as assessed by ACQ	An improvement in FEV1 of >100ml using spirometry.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The identification of exacerbation pathogenesis in patients receiving anti-IL5 therapy via cytokine analysis	Blood cytokine analysis (analysed by Bio-plex 200 system) will be analysed at ad-hoc exacerbation visits to identify exacerbation pathogenesis.	12 months
The identification of exacerbation pathogenesis in patients receiving anti-IL5 therapy via viral throat swab analysis	Viral throat swabs results (using Cepheid Rapid device) will be analysed at ad-hoc exacerbation visits to identify exacerbation pathogenesis.	12 months

Collaborators and Investigators

• Sponsor: University of Nottingham

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 31, 2018
• Primary Completion (ANTICIPATED): June 30, 2021
• Study Completion (ANTICIPATED): July 31, 2021

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (ACTUAL): October 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Asthma; Severe Asthma; Anti-IL5
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: 18048

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No