Efficacy Study in Allergic Rhinitis Patients After Intranasal Administration of AZD8848

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

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.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinitis
• Intervention / Treatment: Drug: AZD8848; Drug: Placebo; Drug: AZD8848 and placebo

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

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Helsingborg, Sweden
    • Research Site
  • Malmohus Lan
    • Lund, Malmohus Lan, Sweden
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of Reflective (10 Min) Total Nasal Symptom Score (TNSS)	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).	During 1st day to 7th day of Allergen challenge period.
Mean of Reflective (10 Min) Total Nasal Symptom Score (TNSS)	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).	During 4th day to 7th day of Allergen challenge period.
Mean of Morning Measurements of Reflective (12 Hrs) Total Nasal Symptom Score (TNSS)	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).	During evening of the 1st day to the morning of the 8th day of Allergen challenge period.
Mean of Evening Measurements of Reflective (12 Hrs) Total Nasal Symptom Score (TNSS)	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).	During the evening of the 1st day to the morning of the 8th day of Allergen challenge period.
Mean of Peak Nasal Inspiratory Flow (PNIF) (10 Min)	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).	During 1st day to 7th day of Allergen challenge period.
Mean of Peak Nasal Inspiratory Flow (PNIF) (10 Min)	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).	During 4th day to 7th day of Allergen challenge period.
Mean of Morning Measurements of Peak Nasal Inspiratory Flow (PNIF) (12 Hrs)	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).	During evening of the 1st day to the morning of the 8th day of Allergen challenge period.
of Evening Measurements of Peak Nasal Inspiratory Flow (PNIF) (12 Hrs)	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).	During evening of the 1st day to the morning of the 8th day of Allergen challenge period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Mean Value of Instantaneous Total Nasal Symptom Score (TNSS)	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.	Pre-dose on visit 2 (baseline)
Absolute Mean Value of Instantaneous Total Nasal Symptom Score (TNSS)	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.	Pre-dose on visit 11 (end of 3rd week of treatment)
Absolute Mean Value of Peak Nasal Inspiratory Flow (PNIF)	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.	Pre-dose on visit 2 (baseline)
Absolute Mean Value of Peak Nasal Inspiratory Flow (PNIF)	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.	Pre-dose on visit 11 (end of 3rd week of treatment)
Change From Baseline of C-X-C Motif Chemokine 10 (CXCL10) in Plasma	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.	Baseline to 1st day of visit 15
Change From Baseline of C-X-C Motif Chemokine 10 (CXCL10) in Nasal Lavage	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.	Baseline to 1st day of visit 15

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Lennart Greiff, MD, PhD, Lund University Hospital, Sweden; Study Director: Sam Lindgren, MD, PhD, AstraZeneca R&D Lund, Sweden

Publications and helpful links

General Publications

• Greiff L, Ahlstrom-Emanuelsson C, Alenas M, Almqvist G, Andersson M, Cervin A, Dolata J, Lindgren S, Martensson A, Young B, Widegren H. Biological effects and clinical efficacy of a topical Toll-like receptor 7 agonist in seasonal allergic rhinitis: a parallel group controlled phase IIa study. Inflamm Res. 2015 Nov;64(11):903-15. doi: 10.1007/s00011-015-0873-2. Epub 2015 Sep 5.

Helpful Links

• CSR Synopsis
• Protocol

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: December 2, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: tolerability; safety; efficacy; allergic rhinitis; nasal symptoms; AZD8848
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: D0540C00014; 2010-020747-13 (EudraCT Number)