Condition category
Respiratory
Date applied
10/12/2015
Date assigned
06/09/2016
Last edited
06/09/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Asthma is a long-term condition which affects the airways. It can affect people of any age, however in usually is first spotted during childhood. When a person is suffering from asthma, the bronchi (tubes which carry air in and out of the lungs) can become narrowed or swollen (inflammation). This causes the sufferer to feel tightness in the chest as the airways become inflamed, causing coughing and difficulty breathing. Most patients with asthma are able to control their condition using medication, however for some patients it is much harder to treat (severe uncontrolled asthma). Xolair is currently licensed in the UK to treat patients with severe asthma but it is clear that not everyone with severe asthma will benefit from treatment. The aim of this study is to investigate the effects of Xolair treatment on the body’s immune system in patients with severe asthma.

Who can participate?
Adults with severe uncontrolled asthma who have had at least two serious attacks in the last year

What does the study involve?
All participants are treated with injections under the skin (subcutaneous injections of Xolair at a dose between 75mg and 600mg, based on their weight, for 52 weeks (standard length of treatment). Participants will stay on their standard, pre-study treatments throughout the 52 weeks. Participants are assessed 16 weeks after starting treatment by their physician to find out how well they are responding to treatment. At the same time, participants provide a urine sample so that it can be tested for levels of a chemical called PGD2 which is produced by certain cells in the immune system in asthma.

What are the possible benefits and risks of participating?
There is a chance that some patients may benefit from better controlled asthma as a result of taking Xolair. There are no notable risks associated with participating.

Where is the study run from?
Southampton General Hospital (lead centre) and 17 other NHS hospitals in the UK.

When is the study starting and how long is it expected to run for?
September 2015 to November 2018

Who is funding the study?
Novartis Pharma AG (UK)

Who is the main contact?
Mr Nicholas Das
somosa@soton.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mr Nicholas Das

ORCID ID

Contact details

MP131 University of Southampton Clinical Trials Unit
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 2381 205154 Ext: 5331
somosa@soton.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

19765

Study information

Scientific title

A study identifying which biomarkers are predictive of a good clinical response following treatment with Xolair in patients with severe asthma

Acronym

Study hypothesis

Primary hypothesis:
Xolair treatment results in significant reduction in the concentrations of 2,3-dinor-11-β-PGF2α in urine after 16 weeks of treatment in patients who respond with a clinical improvement (as judged by GETE evaluation), and in those with long-term clinical benefit (as judged by reduced exacerbations and reduced dose of oral corticosteroids in patients on maintenance oral corticosteroids during 1 year of treatment).

Secondary hypothesis:
The concentration of 2,3-dinor-11-β-PGF2α in urine at baseline is predictive of a good clinical response to Xolair (judged by GETE evaluation and reduced exacerbations during 1 year treatment). Similarly, a change in 2,3-dinor-11-β-PGF2α in urine between baseline and 16 weeks of Xolair treatment is predictive of a good clinical response.

Ethics approval

Wales Research Ethics Committee 5, 24/08/2015, ref: 15/WA/0302

Study design

Interventional non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Respiratory disorders; Subtopic: Respiratory (all Subtopics); Disease: Respiratory

Intervention

All participants will be treated with Xolair 75mg – 600mg as a subcutaneous injection (as per the SmPC guidelines) for a treatment period of 52 weeks. Dosing will be in line with the approved dosing table within the SmPC and will be based on weight and serum IgE.

Participants will stay on their standard, prestudy treatment with inhaled corticosteroids and long acting inhaled steroids. The same will apply to participants who additionally are on maintenance oral corticosteroids. Participants will be assessed 16 weeks after starting treatment with Xolair by their physician using standard evaluation (GETE) and will be defined as “responders” or “non-responders”. The dose of Xolair will only be modified (according to SmPC) if there are significant changes in the patient’s body weight.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Concentration of (PGD2) 2,3-dinor-11-β-PGF2α in urine is measured at baseline and 16 weeks.

Secondary outcome measures

Clinical response to Xolair assessed by GETE at 16 weeks.

Overall trial start date

17/09/2015

Overall trial end date

30/11/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18-70 years
2. Severe uncontrolled asthma (GINA step 4 and 5) despite daily treatment with high-dose inhaled corticosteroids (ICS) and long-acting beta agonists (LABA). (High-dose ICS will be a minimum twice daily dose of 800 mcg of beclomethasone dipropionate equivalent inhaler for at least 8 weeks before screening). Potential participants will need to fulfil the criteria for uncontrolled asthma as judged by their Asthma Control Questionnaire (ACQ) score =1.5 during the screening period.
3. Participants on maintenance treatment with oral corticosteroids will also be included and will also have to meet the same ACQ inclusion criterion (ACQ=1.5)
4. Atopic, as identified by positive skin prick test or in vitro reactivity to a perennial aeroallergen
5. Two or more documented severe asthma exacerbations within the previous 12 months that require courses of prednisolone, defined as increased asthma symptoms requiring treatment in the community or in hospital with systemic corticosteroid rescue therapy or an increase in daily oral corticosteroids for participants already on maintenance oral corticosteroids for >2 months
6. Frequent daytime symptoms or night-time awakenings
7. Reduced lung function (FEV1 <80%) recorded anytime within the past 2 years
8. IgE level of 30 to 1500 IU/mL
9. Body weight less than 150 kg
10. Able to give written informed consent prior to participation in the study, which includes ability to comply with the requirements and restrictions listed in the consent form
11. Able to read, comprehend, and write at a sufficient level to complete study related materials

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 220; UK Sample Size: 220

Participant exclusion criteria

1.An exacerbation requiring treatment with systemic corticosteroids (or an increase in the baseline dose of OCS) within the 30 days before screening
2. Active lung disease other than asthma
3. Treatment with Xolair or another biologic in the 12 months before screening
4. Elevated serum IgE levels for reasons other than allergy (for example, parasite infections, the hyperimmunoglobulin E syndrome, the Wiskott–Aldrich syndrome, or bronchopulmonary aspergillosis)
5. The following medication is not allowed during the run-in and treatment period and should not have been taken for at least 3 months prior to screening: methotrexate, cyclosporine, intravenous immunoglobulin or immunosuppressant’s
6. Current smokeror having smoked in the past year. Ex-smokers will have to be confirmed by a negative cotinine test. If there is a history of smoking for >10 pack years, then asthma diagnosis should have been made before the age of 40 and objective evidence of reversibility of FEV1>12% and 200ml should be available [either previously recorded or done as part of screening for this study]. Potential participants where an asthma/COPD overlap is suspected should not be included.
7. The participant has a history of current recreational drug use or other allergy, which, in the opinion of the responsible physician, contra-indicates their participation
8. Female patient who is pregnant or lactating or up to 6 weeks post partum or 6 weeks cessation of breast feeding
9. Those participants who, in the opinion of the investigator, have a risk of non-compliance with study procedures
10. The participant has a recent history of incapacitating psychiatric disorders
11. History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 4 weeks of baseline assessments (in such participant assessments should be deferred until after 4 weeks have lapsed from the cold)

Recruitment start date

01/10/2015

Recruitment end date

31/03/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Road
NG5 1PB
Nottingham
United Kingdom

Trial participating centre

Gartnavel Hospital
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Wythenshawe Hospital
Southmoor Road Wythenshawe
Manchester
M23 9LT
United Kingdom

Trial participating centre

University College Hospital
Euston Road
London
NW1 2BU
United Kingdom

Trial participating centre

Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom

Trial participating centre

Guy’s Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Birmingham Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Trial participating centre

Bradford Teaching Hospital
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Derriford Hospital Plymouth
Derriford Road
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Royal Liverpool Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

St James Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

Southampton University Hospitals NHS Trust

Sponsor details

Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Novartis Pharma AG

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication of study results in a peer reviewed journal.

Intention to publish date

31/12/2018

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes