SoMOSA: Study of mechanisms of action of omalizumab in severe asthma
| ISRCTN | ISRCTN15124178 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15124178 |
| Secondary identifying numbers | 19765 |
- Submission date
- 10/12/2015
- Registration date
- 06/09/2016
- Last edited
- 31/01/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
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?
Dr Jess Rajaram
somosa@soton.ac.uk
Contact information
Public
MP131
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
| Phone | +44 23 8120 3833 |
|---|---|
| somosa@soton.ac.uk |
Study information
| Study design | Interventional non-randomised study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A study identifying which biomarkers are predictive of a good clinical response following treatment with Xolair in patients with severe asthma |
| 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(s) | Wales Research Ethics Committee 5, 24/08/2015, ref: 15/WA/0302 |
| 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 |
| Primary outcome measure | 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 study start date | 17/09/2015 |
| Overall study end date | 31/08/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 220; UK Sample Size: 220 |
| 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 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 | 28/02/2018 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
Study participating centres
Southampton
SO16 6YD
United Kingdom
Belfast
BT9 7AB
United Kingdom
Oxford
OX3 7LE
United Kingdom
Leicester
LE3 9QP
United Kingdom
NG5 1PB
Nottingham
United Kingdom
Glasgow
G12 0YN
United Kingdom
Sheffield
S10 2JF
United Kingdom
Portsmouth
PO6 3LY
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
London
NW1 2BU
United Kingdom
London
SW3 6NP
United Kingdom
London
SE1 9RT
United Kingdom
Birmingham
B9 5SS
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Liverpool
L7 8XP
United Kingdom
Leeds
LS9 7TF
United Kingdom
Sponsor information
Hospital/treatment centre
Tremona Road
Southampton
SO16 6YD
England
United Kingdom
"ROR" |
https://ror.org/0485axj58 |
|---|
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/08/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication of study results in a peer reviewed journal. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
31/01/2018: Overall trial end date was changed from 30/11/2018 to 31/08/2019 and intention to publish date was changed from 31/12/2018 to 31/08/2020.
29/01/2018: Recruitment end date was changed from 29/12/2017 to 28/02/2018.
11/04/2017: The study contact has changed from Nicholas Das to Jess Rajaram. In addition, the recruitment end date has been updated from 31/03/2017 to 29/12/2017.
