Omalizumab in Non-atopic Asthma

NCT01113437 | Unknown Phase 2 DMC

• 2 other identifiers: 09/H0804/432009-009154-25
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Hypothesis- Omalizumab(humanized monoclonal anti-IgE antibody)improves disease control and reduces bronchial mucosal inflammation in non-atopic asthma. In order to test the above hypothesis, the investigators propose a placebo controlled, double blind, parallel group study to obtain proof of principle that omalizumab exerts beneficial effects on disease control in non-atopic severe adult asthmatics aged 18-60 years . Forty patients will be randomized in a 1:1 ratio to receive omalizumab or matching placebo. Following 12 weeks of treatment with omalizumab/placebo, and as this treatment is continued for a further 8 weeks, anti-asthma treatment will be reduced. Dosages will be administered at 4 or 2 weekly intervals over a 16 week period (5 or 10 doses in total), which corresponds with the time stated as necessary to judge efficacy of therapy according to omalizumab's licensed indications in atopic asthma. Efficacy will be judged by clinical monitoring and by bronchial biopsy to assess effects on bronchial inflammation and local IgE production.

Conditions

Bronchial Asthma

Keywords

Bronchial Asthma; Allergy

Outcome Measures

Primary Outcomes (2)

• Pre-bronchodilator FEV1

  Prior to reduction of existing anti-asthma therapy (first 12 weeks of study): • Pre-bronchodilator FEV1 (primary outcome measure)

  before and after treatment with omalizumab for 16 weeks

• Disease exacerbation

  During anti-asthma therapy reduction phase (subsequent 8 weeks of study): The primary outcome measure during asthma therapy reduction phase will be disease exacerbation defined as a need for rescue oral corticosteroid medication for worsening of symptoms and/or deterioration in lung function, as agreed between the patient and the study physician

  From week 12 to week 20 of the study

Secondary Outcomes (8)

• Day and night time symptom scores

  before and after treatment with omalizumab for 16 weeks

• Morning and evening peakflows

  before and after treatment with omalizumab for 16 weeks

• Exhaled nitric oxide

  before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)

• Total dosage of rescue beta-2-agonists

  before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)

• Total symptom free days

  before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)

Study Arms (2)

Omalizumab

EXPERIMENTAL

There are 2 arms of the study; patients in one arm receiving omalizumab and in the other arm receiving placebo.

Drug: Omalizumab

Placebo

PLACEBO COMPARATOR

There are 2 arms of the study; patients in one arm receiving omalizumab and in the other arm receiving placebo.

Drug: Placebo

Interventions

Omalizumab DRUG

Omalizumab or placebo by subcutaneous injections, at 4 weekly or 2 weekly intervals. Dosage is according to manufacturer's guidance and calculated based on body weight and total serum IgE.

Also known as: Xolair

Omalizumab

Placebo DRUG

Omalizumab or placebo by subcutaneous injections, at 4 weekly or 2 weekly intervals. Dosage is according to manufacturer's guidance and calculated based on body weight and total serum IgE.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females aged 18 to 60 years inclusive.
• Moderate or severe non-atopic asthma as defined below treated with inhaled corticosteroids for at least 6 months.
• Daytime and nighttime symptoms at least 3 days per week in the last 3 months prior to screening visit(despite taking inhaled corticosteroids with or without beta-2-agonists or leukotriene blockers.
• Pre-bronchodilator FEV1 40-80% of the predicted; reversibility equal to or more than 12% in response to inhaled beta-2-agonists documented at any time within the past 2 years.
• Negative skin prick and/or in vitro IgE tests to a range of 12 common aeroallergens(pollens:grass, hazel, alder, birch; danders: cat, dog; dust mite: D.pteronyssinus, D.farinae; moulds: Cladosporium, Aspergillus, Alternaria).

You may not qualify if:

• Smoking within the past year or total smoking history more than 0.5 pack years.
• Pregnant or lactating females or those at risk of pregnancy.
• Treatment with more than 2000 mcg/day beclometasone, 1600 mcg/day budesonide or 1000 mcg/day fluticasone by inhalation or regular systemic corticosteroid at screening.
• Hospitalization for asthma or exacerbation requiring systemic corticosteroid therapy within 3 months of the screening visit.
• History of life threatening asthma, defined as an asthma episode that required intubations and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures.
• Patients in whom, in the opinion of the study investigators, omalizumab therapy might normally require precaution (history of autoimmune disease, renal or hepatic impairment, hyperimmunoglobulin E syndrome, allergic bronchopulmonary aspergillosis and diabetes mellitus)

Sponsors & Collaborators

• King's College London: lead

Study Sites (2)

London Chest Hospital

London, E2 9JX, United Kingdom

NOT YET RECRUITING

Guy's Hospital, London, UK

London, SE1 9RT, United Kingdom

RECRUITING

Related Publications (1)

• Pillai P, Chan YC, Wu SY, Ohm-Laursen L, Thomas C, Durham SR, Menzies-Gow A, Rajakulasingam RK, Ying S, Gould HJ, Corrigan CJ. Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma. Eur Respir J. 2016 Dec;48(6):1593-1601. doi: 10.1183/13993003.01501-2015. Epub 2016 Oct 20.

  PMID: 27824606 DERIVED

MeSH Terms

Conditions

Asthma; Hypersensitivity

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Officials

• Christopher Corrigan, MD, PhD

  King's College, London, UK

  PRINCIPAL INVESTIGATOR

• Neil Barnes, MD

  London Chest Hospital, UK

  PRINCIPAL INVESTIGATOR

• Prathap Pillai, MD

  King's College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher Corrigan, MD,PhD

CONTACT

00-44-2071880610; chris.corrigan@kcl.ac.uk

Prathap Pillai, MD

CONTACT

00-44-2071880606; prathap.pillai@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 26, 2010
• First Posted: April 29, 2010
• Study Start: April 1, 2010
• Primary Completion: August 1, 2012
• Last Updated: January 21, 2011

Record last verified: 2010-04

Locations

GB (2)