E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective: To compare the efficacy of 60 μg AZD8848 once weekly with 20 μg AZD8848 three (3) times weekly and with placebo when administered intranasally to seasonal allergic rhinitis patients out of season in a nasal allergen challenge model. |
|
E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
- To investigate the tolerability and safety of AZD8848 administered intranasally up to three (3) times weekly for one month to seasonal allergic rhinitis patients out of season.
- To investigate the pharmacodynamic effects of AZD8848 on systemic and local biomarkers.
- To investigate the influence of butyrylcholinesterase genotype on pharmacodynamic responses where appropriate. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The participation in the genetic research activity is an optional part of the study. Patients must give separate informed consent before a blood sample is taken. Pharmacogenetic data will be reported separately from the Clinical Study Report.
Objective: - To investigate the influence of butyrylcholinesterase genotype on pharmacodynamic responses where appropriate.
|
|
E.3 | Principal inclusion criteria |
For inclusion in the study patients should fulfil the following criteria:
1. Provision of signed and dated informed consent prior to any study specific procedures 2. Female and/or male patients, aged 18 to 55 years inclusive. Females must be of non-childbearing potential or must have been stable on highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue on the chosen method, with additional use of a condom by male partner, until 3 months after the last dose 3. Females must have a negative pregnancy test and a date of last menstruation consistent with non-pregnancy at Visit 1 4. Have a body mass index (BMI) between 19 and 30 kg/m2 and a weight between 50 and 100 kg 5. Seasonal allergic rhinitis patients out of pollen season 6. Have a history of birch and/or timothy grass pollen induced seasonal allergic rhinitis for at least the previous 2 years 7. Have presence of allergic sensitivity to birch and/or timothy grass pollen verified by a positive skin prick test documented within the previous 24 months or at Visit 1 8. Have a need of treatment for their nasal symptoms during the pollen season 9. Have reaction to an individually titrated dose of nasal allergen resulting in at least 5 sneezes and/or recorded score of 2 or more on a scale from 0 to 3 in either of the symptoms nasal blockage or runny nose 10. Be able to metabolise AZD8848 (an in vitro screening assay will determine BChE activity in a blood sample taken at Visit 1 using a pre-defined limit)
|
|
E.4 | Principal exclusion criteria |
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
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 2. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, 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 3. QTcF > 450 ms (confirmed with repeated measurements) at Visit 1 4. Rhythm, conduction (e.g. intermittent or constant Bundle branch block; Intraventricular conduction disturbance with repolarization changes; intermittent or constant AV block [including 1st degree AV block with PR interval > 220 msec, 2nd or 3rd degree AV block]); or morphologic changes affecting repolarization (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 5. History of additional risk factors for Torsade de pointes (eg, heart failure, hypokalemia, family history of Long QT syndrome, or sudden death) 6. Medical history suggesting or confirming abnormal immune function, apart from allergic rhinitis 7. Family history (parent or sibling) of autoimmune disease including, but not limited to, Wegeners granulomatosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren´s syndrome, multiple sclerosis, autoimmune thrombocytopenia, primary biliary cirrhosis, Mb Crohn, ulcerative colitis, type 1 diabetes or other autoimmune disease considered relevant by the Investigator 8. History of asthma 9. Symptomatic perennial allergic or non-allergic rhinitis, except for cat and dog sensitivity under the condition that these patients will not be exposed to cats and dogs during the study up until Visit 16, as judged by the Investigator 10. History of or ongoing immunotherapy, including but not limited to specific immunotherapy (SIT) 11. Topical or inhaled glucocorticosteroid treatment within 1 month prior to Visit 1 12. Systemic glucocorticosteroid therapy for any reason during 6 weeks prior to Visit 1 13. Antihistamine treatment within 1 week prior to Visit 1 14. Use of any medication (including vaccinations, over-the-counter drugs, herbal medicines and nutritional supplements,) or therapy within 2 weeks prior to Visit 2 (or longer if the medication has a half-life long enough to 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 occasional intake of paracetamol 15. Suspicion of Gilbert’s syndrome 16. A suspected/manifested infection according to World Health Organisation (WHO) risk groups 2, 3, or 4 17. Positive results on screening tests for serum Hepatitis B surface antigen, Hepatitis C antibodies, and/or HIV 18. Any upper respiratory tract infection (bacterial, viral or fungal infections of the airways) or any other clinically significant illness within 2 weeks prior to Visit 2 being symptomatic enough to affect study conduct or the wellbeing of the patient as judged by the Investigator 19. Structural abnormalities of the nose or nasal disorder symptomatic enough to cause significant nasal obstruction as judged by the Investigator 20. Known or suspected hypersensitivity to investigational drug or any excipients 21. Definite or suspected personal history of significant adverse drug reactions/any anaphylactic reaction 22. Use of drugs with CYP3A4 enzyme inducing properties, including herbal medicines such as St John’s Worth, within 3 weeks prior to Visit 2 23. History of or current alcohol and/or drug abuse, as judged by the Investigator, or positive drugs of abuse test 24. Planned surgery, dental procedure, or hospitalization during the study, and/or major surgery or significant trauma within 3 months of Visit 1 25. Participation in another study within 3 months before the start of the present study (or within 1 month for methodology studies in which no drugs were administered) 26. Donation of blood within 2 months prior to Visit 1 or donation of more than 1350 mL within 12 months prior to Visit 1 27. Patients who, in the opinion of the Investigator, should not participate in the study 28. Pregnancy or lactation 29. Detection of anti-PR3 autoantibodies in the blood 30. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study centre) 31. Previous randomisation of treatment in the present study 32. History of habitual nicotine use equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day), as judged by the Investigator
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: - Reflective Total Nasal Symptom Score (TNSS) during allergen challenge - Peak Nasal Inspiratory Flow (PNIF) during allergen challenge
Pharmacodynamics: - Blood: CXCL-10 (IP-10) and additional exploratory biomarkers - Nasal lavage: CXCL-10 (IP-10), myeloperoxidase, α2-macroglobulin, tryptase, eosinophilic cationic protein (ECP) and additional exploratory biomarkers
Safety: - Incidence and nature of Adverse Events - Instantaneous Total Nasal Symptom Score (TNSS) during treatment period - Peak Nasal Inspiratory Flow (PNIF) during treatment period - Electrocardiogram parameters, blood pressure, pulse, physical examination, clinical chemistry, haematology, urinalysis, clinical inspection of the nose, auto-antibodies
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study is defined as final data base lock which will be performed after the last telephone contact has been completed (Visit 19). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |