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

NCT ID: NCT01948401

Last Updated: 2016-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2014-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Asthma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Blinding Strategy

NONE

Study Groups

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Controlled asthma

Group Type EXPERIMENTAL

LABA

Intervention Type DRUG

long-acting beta-agonist treatment

corticosteroids

Intervention Type DRUG

chronic treatment with oral corticosteroids, high dose inhaled corticosteroids

Uncontrolled asthma with additional OCS

Group Type EXPERIMENTAL

LABA

Intervention Type DRUG

long-acting beta-agonist treatment

corticosteroids

Intervention Type DRUG

chronic treatment with oral corticosteroids, high dose inhaled corticosteroids

prednisolone

Intervention Type DRUG

additional 0.5 mg/kg orally for 7 days

Uncontrolled asthma without additional OCS

Group Type EXPERIMENTAL

LABA

Intervention Type DRUG

long-acting beta-agonist treatment

corticosteroids

Intervention Type DRUG

chronic treatment with oral corticosteroids, high dose inhaled corticosteroids

Interventions

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LABA

long-acting beta-agonist treatment

Intervention Type DRUG

corticosteroids

chronic treatment with oral corticosteroids, high dose inhaled corticosteroids

Intervention Type DRUG

prednisolone

additional 0.5 mg/kg orally for 7 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Initiation of or change in allergen immunotherapy within three months before the time of informed consent
* Treatment with an investigational agent within 30 days of informed consent or 5 half-lives of the investigational agent, whichever is longer
* Pregnant or lactating women
* Body mass index (BMI) \>38 kg/m2
* Body weight \<40 kg
Minimum Eligible Age

12 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Belfast, , United Kingdom

Site Status

Birmingham, , United Kingdom

Site Status

Glasgow, , United Kingdom

Site Status

Glasgow, , United Kingdom

Site Status

Hampshire, , United Kingdom

Site Status

Leicester, , United Kingdom

Site Status

London, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Newcastle upon Tyne, , United Kingdom

Site Status

Nottingham, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 30940770 (View on PubMed)

Other Identifiers

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WB28850

Identifier Type: -

Identifier Source: org_study_id