Efficacy Study in Allergic Rhinitis Patients After Intranasal Administration of AZD8848

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01185080
First received: August 11, 2010
Last updated: December 2, 2015
Last verified: December 2015
  Purpose
The primary purpose of this study is to investigate effect, tolerability and safety of different dosing regimens of AZD8848 administered intranasally to seasonal allergic rhinitis patients out of season in an allergen challenge model.

Condition Intervention Phase
Allergic Rhinitis
Drug: AZD8848
Drug: Placebo
Drug: AZD8848 and placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo Controlled, Randomised, Parallel Group Phase IIa Study to Investigate the Efficacy, Tolerability, and Safety of Different Dosing Regimens of AZD8848 Administered Intranasally to Seasonal Allergic Rhinitis Patients Out of Pollen Season in a Nasal Allergen Challenge Model

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Mean of Reflective (10 Min) Total Nasal Symptom Score (TNSS) [ Time Frame: During 1st day to 7th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of Reflective Total Nasal Symptom Score (absolute values) for symptoms over the last 10 minutes after allergen challenge, collected during clinic visits. The Mean is calculated over the Allergen challenge period, which is a seven day period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome.

    Allergen challenge period starts 24 hrs post last dose (visit 15). Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • Mean of Reflective (10 Min) Total Nasal Symptom Score (TNSS) [ Time Frame: During 4th day to 7th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of Reflective Total Nasal Symptom Score (absolute values) for symptoms over the last 10 minutes after allergen challenge, collected during clinic visits. The Mean is calculated over 4th day to 7th day of the Allergen challenge period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome. Allergen challenge period starts 24 hrs post last dose.

    Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • Mean of Morning Measurements of Reflective (12 Hrs) Total Nasal Symptom Score (TNSS) [ Time Frame: During evening of the 1st day to the morning of the 8th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of morning measurements of Reflective Total Nasal Symptom Score (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome.

    Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • Mean of Evening Measurements of Reflective (12 Hrs) Total Nasal Symptom Score (TNSS) [ Time Frame: During the evening of the 1st day to the morning of the 8th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of evening measurements of Reflective Total Nasal Symptom Score (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome.

    Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • Mean of Peak Nasal Inspiratory Flow (PNIF) (10 Min) [ Time Frame: During 1st day to 7th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of Peak Nasal Inspiratory Flow (absolute values) recorded immediately after TNSS scoring (recall period 10 min), during Allergen challenge period. The Mean is calculated over the Allergen challenge period, which is a seven day period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded.

    Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • Mean of Peak Nasal Inspiratory Flow (PNIF) (10 Min) [ Time Frame: During 4th day to 7th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of Peak Nasal Inspiratory Flow (absolute values) recorded immediately after TNSS scoring (recall period 10 min), during Allergen challenge period. The Mean is calculated over 4th day to 7th day of the Allergen challenge period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded.

    Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • Mean of Morning Measurements of Peak Nasal Inspiratory Flow (PNIF) (12 Hrs) [ Time Frame: During evening of the 1st day to the morning of the 8th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of morning measurements of Peak Nasal Inspiratory Flow (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded.

    Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).


  • of Evening Measurements of Peak Nasal Inspiratory Flow (PNIF) (12 Hrs) [ Time Frame: During evening of the 1st day to the morning of the 8th day of Allergen challenge period. ] [ Designated as safety issue: No ]

    Mean of evening measurements of Peak Nasal Inspiratory Flow (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded.

    Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).



Secondary Outcome Measures:
  • Absolute Mean Value of Instantaneous Total Nasal Symptom Score (TNSS) [ Time Frame: Pre-dose on visit 2 (baseline) ] [ Designated as safety issue: No ]

    Absolute mean value of Instantaneous Total Nasal Symptom Score (TNSS) for pre-dose symptoms on visit 2, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicate worse outcome.

    Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 2.


  • Absolute Mean Value of Instantaneous Total Nasal Symptom Score (TNSS) [ Time Frame: Pre-dose on visit 11 (end of 3rd week of treatment) ] [ Designated as safety issue: No ]

    Absolute mean value of Instantaneous Total Nasal Symptom Score (TNSS) for pre-dose symptoms on visit11, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome.

    Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 11.


  • Absolute Mean Value of Peak Nasal Inspiratory Flow (PNIF) [ Time Frame: Pre-dose on visit 2 (baseline) ] [ Designated as safety issue: No ]

    Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) for pre-dose symptoms on visit 2, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded.

    Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 2.


  • Absolute Mean Value of Peak Nasal Inspiratory Flow (PNIF) [ Time Frame: Pre-dose on visit 11 (end of 3rd week of treatment) ] [ Designated as safety issue: No ]

    Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) for pre-dose symptoms on visit 11, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded.

    Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 11.


  • Change From Baseline of C-X-C Motif Chemokine 10 (CXCL10) in Plasma [ Time Frame: Baseline to 1st day of visit 15 ] [ Designated as safety issue: No ]

    Change from baseline to 24 hours after last dose (day1 visit 15) of C-X-C motif chemokine 10 (CXCL10) in plasma, expressed as a ratio. The ratio is calculated as day1 of visit 15 / baseline.

    Number of Participants Analyzed is based on all patients with evaluable biomarker data at visit 2 and visit15.


  • Change From Baseline of C-X-C Motif Chemokine 10 (CXCL10) in Nasal Lavage [ Time Frame: Baseline to 1st day of visit 15 ] [ Designated as safety issue: No ]

    Change from baseline to 24 hours after last dose (day1 visit 15) of C-X-C motif chemokine 10 (CXCL10) in nasal lavage, expressed as a ratio. The ratio is calculated as day1 of visit 15 / baseline.

    Number of Participants Analyzed is based on all patients with evaluable biomarker data at visit 2 and visit 15.



Enrollment: 93
Study Start Date: September 2010
Study Completion Date: January 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. AZD8848
20 μg AZD8848 three times weekly
Drug: AZD8848
Nasal spray solution, intranasal, three times weekly for one month
Placebo Comparator: 2. Placebo
Placebo three times weekly
Drug: Placebo
Nasal spray solution, intranasal, three times weekly for one month
Experimental: 3. AZD8848 and placebo
60 μg AZD8848 once weekly and placebo twice weekly
Drug: AZD8848 and placebo
Nasal spray solution, intranasal, three times weekly for one month

Detailed Description:
A double-blind, placebo controlled, randomised, parallel group phase IIa study to investigate the efficacy, tolerability, and safety of different dosing regimens of AZD8848 administered intranasally to seasonal allergic rhinitis patients out of pollen season in a nasal allergen challenge model
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Seasonal allergic rhinitis patients out of pollen season
  • Have a history and presence of birch and/or timothy grass pollen induced seasonal allergic rhinitis for at least the previous 2 years (verified by a positive skin prick test)
  • Patients with need of treatment for their nasal symptoms during the pollen season

Exclusion Criteria:

  • Symptomatic perennial allergic or non-allergic rhinitis
  • Family history of autoimmune disease A history of asthma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185080

Locations
Sweden
Research Site
Lund, Malmohus Lan, Sweden
Research Site
Helsingborg, Sweden
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Lennart Greiff, MD, PhD Lund University Hospital, Sweden
Study Director: Sam Lindgren, MD, PhD AstraZeneca R&D Lund, Sweden
  More Information

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01185080     History of Changes
Other Study ID Numbers: D0540C00014  2010-020747-13 
Study First Received: August 11, 2010
Results First Received: August 31, 2015
Last Updated: December 2, 2015
Health Authority: Sweden: Medical Products Agency

Keywords provided by AstraZeneca:
AZD8848
allergic rhinitis
efficacy
tolerability
safety
nasal symptoms

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 28, 2016