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

• ClinicalTrials.gov Identifier: NCT01948401
• Recruitment Status: Completed
• First Posted: September 23, 2013
• Last Update Posted: November 2, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 6, 2013
• First Posted Date: September 23, 2013
• Last Update Posted Date: November 2, 2016
• Study Start Date: July 2013
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 18, 2013): Serum periostin levels [ Time Frame: up to 95 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 20, 2014)

• Asthma quality of life questionnaire for adults and adolescents aged 12 years and older (AQLQ12+) [ Time Frame: up to 95 days ]
• IL-13 related biomarker levels [ Time Frame: up to 95 days ]
• Lung function: Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) [ Time Frame: up to 95 days ]
• Safety: Incidence of adverse events [ Time Frame: up to 95 days ]
• Patient reported outcomes: Asthma Control Questionnaire (ACQ-7) [ Time Frame: up to 95 days ]

Original Secondary Outcome Measures (submitted: September 18, 2013)

• IL-13 related biomarker levels [ Time Frame: up to 95 days ]
• Lung function: Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) [ Time Frame: up to 95 days ]
• Safety: Incidence of adverse events [ Time Frame: up to 95 days ]
• Patient reported outcomes: Asthma Control Questionnaire (ACQ-7) [ Time Frame: up to 95 days ]
• Asthma quality of life questionnaire for adults and adolescents aged 12 years and older (AQLQ12+) [ Time Frame: up to 95 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Measure Serum Periostin, Asthma-Related Biomarkers and Response to Prednisolone in Adult and Adolescent Patients With Severe Oral Corticosteroid-Dependent Asthma
• Official Title: A STUDY TO MEASURE SERUM PERIOSTIN, ASTHMA-RELATED BIOMARKERS AND RESPONSE TO PREDNISOLONE IN ADULT AND ADOLESCENT PATIENTS WITH SEVERE ORAL CORTICOSTEROID-DEPENDENT ASTHMA
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label)
• Condition: Asthma

Intervention

• Drug: LABA
  long-acting beta-agonist treatment
• Drug: corticosteroids
  chronic treatment with oral corticosteroids, high dose inhaled corticosteroids
• Drug: prednisolone
  additional 0.5 mg/kg orally for 7 days

Study Arms

• Experimental: Controlled asthma
  Interventions:

  • Drug: LABA
  • Drug: corticosteroids
• Experimental: Uncontrolled asthma with additional OCS
  Interventions:

  • Drug: LABA
  • Drug: corticosteroids
  • Drug: prednisolone
• Experimental: Uncontrolled asthma without additional OCS
  Interventions:

  • Drug: LABA
  • Drug: corticosteroids

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 1, 2015): 54
• Original Estimated Enrollment (submitted: September 18, 2013): 97
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01948401
• Other Study ID Numbers: WB28850
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: November 2016