A double-blind, placebo controlled, randomised, parallel group, single centre, phase IIa study to investigate the efficacy, tolerability and safety of 8 doses of AZD8848 administered intranasally once weekly in mild to moderate allergic asthma patients challenged with an inhaled allergen.
- Conditions
- Allergic AsthmaMedDRA version: 12.0 Level: LLT Classification code 10001705 Term: Allergic asthma
- Registration Number
- EUCTR2009-013705-34-GB
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Provision of informed consent prior to any study specific procedures
2. Male or female patients aged 18 to 55 years (inclusive). Females must be of non-childbearing potential or must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue on the chosen contraceptive method, with additional use of a condom, until Visit 19. Women must be non-lactating and must have a date of menstruation consistent with non-pregnancy (see section 4.1.2 for more details)
3. A minimum of 6 months documented history of asthma defined according to the
GINA guidelines (Global Initiative for Asthma 2008) prior to Visit 1
4. The presence of allergic sensitivity (grass, house dust mite, cat) verified by a
positive skin prick test documented within the previous 24 months or at Visit 1
5. FEV1 (forced expiratory volume in 1 second) >70% of predicted normal value,
prebronchodilator
6. The presence of an Early Asthmatic Response corresponding to = 20% FEV1
decrease within 2 hours post-allergen challenge as verified and documented within
the previous 12 months or at screening. The inhaled allergen will be one of those giving a positive response in the skin prick test (see section 6.2.1).
7. Methacholine PC20 (the provocative concentration of methacholine causing a 20%
fall in FEV1) <16 mg/mL as verified and documented within the previous 12
months or at screening (Visit 1)
8. Body mass index between 19 and 33 kg/m2
9. Non- or ex-smokers who are expected to not smoke for the duration of the trial up
to Visit 12 (an ex-smoker being defined as someone who <10 pack-year history and
who has completely stopped smoking for at least 6 months before Visit 1)
10. Ability to metabolise AZD8848 (an in vitro screening assay will determine esterase metabolic activity in a blood sample taken at Visit 1 using a pre-defined limit)
For inclusion in the main part, note the additional criteria for LAR:
6. Early Asthmatic Response corresponding to =20% FEV1 decrease within 2 hours
and Late Asthmatic Response corresponding to =15 % FEV1 decrease between 4-10
hours post-allergen challenge on two consecutive occasions. The inhaled allergen
will be the one of those giving a positive response in the skin prick test (see section 6.2.1).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Any clinically relevant disease and/or abnormality (past or present), which, in the
opinion of the Investigator, may either put the patient at risk because of
participation in the study, or influence the results of the study, or the patient’s
ability to participate in the study. Includes pregnant or lactating females.
2. Symptomatic allergic rhinitis (those with a history of allergic rhinitis may
participate if asymptomatic at screening and if, in the opinion of the Investigator, it
is unlikely that disease exacerbation will occur during the course of the study)
3. Any clinical relevant abnormal findings in physical examination, clinical chemistry,
haematology, urinalysis, vital signs, or ECG at baseline which, in the opinion of the
investigator, may put the patient at risk because of participation in the study
4. QTcF >450ms, confirmed with repeated measurements at Visit 1
5. Rhythm, conduction (eg intermittent or constant Bundle branch block;
Intraventricular conduction disturbance with repolarisation changes: intermittent or
constant AV block (including 1st degree AV block with PR interval >220msec, 2nd
or 3rd degree AV block)); or morphologic changes affecting repolirization (eg, flat,
biphasic or inverted T waves in primary lead V2), that may limit ability to measure
QTc and assess changes in QTc intervals or QTc morphology
6. History of additional risk factors for Torsade de pointes (eg heart failure,
hypokaelamia, family history of Long QT syndrome, or sudden death)
7. Medical history suggesting or confirming abnormal immune function, except for
asthma
8. Family history (parent or sibling) of autoimmune disease including but not limited
to Wegener’s granulomatosis, system lupus erythematosus, rheumatoid arthritis,
Sjögren’s syndrome, multiple sclerosis, autoimmune thrombocytopenia, primary
biliary cirrhosis or any other autoimmune disease considered clinically relevant by
the investigator
9. Any detection of anti-PR3 autoantibodies in the blood
10. History of or ongoing immunotherapy
11. Topical or inhaled glucocorticosteroid +/- Long-Acting ß-Agonists (LABAs)
treatment within 4 weeks prior to Visit 1
12. Systemic glucocorticosteroid therapy for any reason within 6 weeks prior to Visit 1
13. Antihistamine treatment within 1 week prior to Visit 1. This period should be extended for antihistamines with a long half-life (see exclusion criteria 14)
14. Use of any medication (including vaccinations, over the counter drugs and herbal medicines such as St John's Wort) or therapy within 2 weeks prior to Visit 1 which may potentially expose the patient to any significant systemic exposure
that may interfere with the objectives of the study or the safety of the patients as
judged by the investigator, except for inhaled short-acting ß2 agonists for treatment
of asthma symptoms and occasional intake of paracetamol
15. An exacerbation of asthm
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method