A Study to Measure Serum Periostin, Asthma-Related Biomarkers and Response to Prednisolone in Adult and Adolescent Patients With Severe Oral Corticosteroid-Dependent Asthma

NCT01948401 | Completed Phase 2

• 1 other identifier: WB28850
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 11

Brief Summary

This interventional, open study will evaluate clinical data in relation to biomarkers in patients 12 to 75 years of age with severe oral corticosteroid (OCS) - dependent asthma. Patients with uncontrolled asthma will be offered an additional escalation of OCS at a dose of 0.5 mg/kg for 7 days. Patients enrolled in this study would be eligible to be enrolled in a future placebo-controlled intervention study designed to measure the steroid-sparing effect of lebrikizumab.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Serum periostin levels

  up to 95 days

Secondary Outcomes (5)

• Asthma quality of life questionnaire for adults and adolescents aged 12 years and older (AQLQ12+)

  up to 95 days

• IL-13 related biomarker levels

  up to 95 days

• Lung function: Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)

  up to 95 days

• Safety: Incidence of adverse events

  up to 95 days

• Patient reported outcomes: Asthma Control Questionnaire (ACQ-7)

  up to 95 days

Study Arms (3)

Controlled asthma

EXPERIMENTAL

Drug: LABA; Drug: corticosteroids

Uncontrolled asthma with additional OCS

EXPERIMENTAL

Drug: LABA; Drug: corticosteroids; Drug: prednisolone

Uncontrolled asthma without additional OCS

EXPERIMENTAL

Drug: LABA; Drug: corticosteroids

Interventions

LABA DRUG

long-acting beta-agonist treatment

Controlled asthma; Uncontrolled asthma with additional OCS; Uncontrolled asthma without additional OCS

corticosteroids DRUG

chronic treatment with oral corticosteroids, high dose inhaled corticosteroids

Controlled asthma; Uncontrolled asthma with additional OCS; Uncontrolled asthma without additional OCS

prednisolone DRUG

additional 0.5 mg/kg orally for 7 days

Uncontrolled asthma with additional OCS

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult and adolescent patients , \>/=12 to \</=75 years of age at the time of informed consent
• Severe asthma (as defined by GINA step 5 classification of asthma severity) after a detailed systematic assessment (the BTS UK Difficult Asthma Network assessment model \[Heaney et al 2010\] or equivalent) and follow-up by an asthma specialist for at least six months
• History of asthma treatment with high doses of inhaled corticosteroids (ICS ) (\>/=1500 mcg beclomethasone dipropionate daily, or equivalent) and long-acting beta-2 agonists (LABAs), with or without an additional controller, for at least six months before Screening
• Chronic treatment with maintenance oral corticosteroids (OCS) for at least six months before the time of informed consent ; (baseline OCS dose: adults 10 to 40 mg/day, adolescents 5 to 40 mg/day daily dose equivalent)
• Compliance with OCS therapy will be based on prior detectable levels of serum prednisolone, cortisol suppression, or observation of Cushingoid appearance consistent with regular systemic steroid use
• Diagnosis of refractory asthma (Heaney et al 2010) with OCS dependence on minimal effective or maximum tolerated dose
• Confirmed (by chest x-ray) absence of other significant lung disease
• Documented history of bronchodilator reversibility response of \>/=12% and \>/=200 mL within the past 12 months before the time of informed consent

You may not qualify if:

• Baseline FEV1 \</=39% of predicted
• Asthma exacerbation (as defined by protocol) within 28 days before the time of informed consent or during Screening
• Major episode of infection requiring admission to hospital for \>/=24 hours or treatment with intravenous antibiotics within the 28 days before the time of informed consent or during Screening or requiring treatment with oral antibiotics within the 14 days before the time of informed consent or during Screening
• Active parasitic infection or Listeria monocytogenes infection within the 6 months before the time of informed consent
• For adults active tuberculosis (TB) requiring treatment within the 12 months before the time of informed consent (patients are also required to have no recurrence of symptoms in the 12 months following completion of TB treatment), or for adolescents history of active TB requiring treatment
• Known history of severe clinically significant immunodeficiency
• Evidence of acute or chronic hepatitis or known liver cirrhosis
• Inadequate liver function
• Diagnosis or history of malignancy, or current investigation for possible malignancy
• Other clinically significant medical disease that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy or affect the ability to participate in the study
• Current smoker or former smoker with a smoking history of \>15 pack-years
• Current use of an immunomodulatory/immunosuppressive therapy or past use within three months or five drug half-lives (whichever is longer) before the time of informed consent
• Use of a biologic therapy (including omalizumab) at any time during the 4 months before the time of informed consent
• History of anaphylaxis with omalizumab treatment or history of anaphylaxis to any therapeutic biological agent
• Use of zileuton or roflumilast at any time during the two months before the time of informed consent

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (11)

Unknown Facility

Belfast, BT9 7AB, United Kingdom

Location

Unknown Facility

Birmingham, B9 5SS, United Kingdom

Location

Unknown Facility

Glasgow, G12 0XH, United Kingdom

Location

Unknown Facility

Glasgow, G21 3UW, United Kingdom

Location

Unknown Facility

Hampshire, SO16 6YD, United Kingdom

Location

Unknown Facility

Leicester, LE3 9QP, United Kingdom

Location

Unknown Facility

London, EC1A 7BE, United Kingdom

Location

Unknown Facility

London, SW3 6NP, United Kingdom

Location

Unknown Facility

Manchester, M23 9LT, United Kingdom

Location

Unknown Facility

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Unknown Facility

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• Busby J, Holweg CTJ, Chai A, Bradding P, Cai F, Chaudhuri R, Mansur AH, Lordan JL, Matthews JG, Menzies-Gow A, Niven R, Staton T, Heaney LG. Change in type-2 biomarkers and related cytokines with prednisolone in uncontrolled severe oral corticosteroid dependent asthmatics: an interventional open-label study. Thorax. 2019 Aug;74(8):806-809. doi: 10.1136/thoraxjnl-2018-212709. Epub 2019 Apr 2.

  PMID: 30940770 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Adrenal Cortex Hormones; Prednisolone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 23, 2013
• Study Start: July 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

GB (11)