Azelastine Allergen Chamber - Onset of Action Study

Randomized, Double-blind, Cross-over Clinical Trial to Assess Onset of Action and Efficacy of Azelastine Hydrochloride 0.15% Nasal Spray in the Treatment of Allergen-Induced Allergic Rhinitis Symptoms in an Environmental Exposure Unit in Comparison to Placebo and Mometasone Furoate/Olopatadine Hydrochloride Nasal Spray

This study is to assess the Onset of Action and Efficacy of azelastine hydrochloride 0.15% in treating the nasal symptoms of seasonal allergic rhinitis (SAR) induced by an allergen challenge in an Environmental Exposure Unit (EEU) followed by a single dose and a 3-day treatment at home.

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Mississauga, Ontario, Canada, L4W1A4
      • Cliantha Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Male or female subjects (childbearing and non-childbearing potential, non-childbearing potential defined as females with no menstruation for at least 1 year at screening and documented FSH > 35 IU/L) aged 18 to 55 years (inclusive) at screening.
• History of SAR to ragweed pollen for at least the previous 2 ragweed pollen seasons.
• Positive skin prick test (SPT) response to ragweed pollen (allergen induced wheal diameter at least 3 mm larger than the negative control). A test performed at Cliantha Research in the previous 12 months may be used to qualify the subject.

Main Exclusion Criteria:

Safety Concerns:

• History of allergic reaction to azelastine hydrochloride, olopatadine hydrochloride, mometasone furoate, or one of the excipients / components of the study treatments
• History of anaphylaxis, cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, metabolic, psychiatric, neurological, or other disease at screening that may affect subject safety during the study or evaluation of the study endpoints at the discretion of the Investigator and/or designee.
• Subjects with a current diagnosis of asthma or subjects with measured forced expiratory volume in 1 second (FEV1) <75% of the predicted value using Global Lung Function Initiative set from 2012 for references.
• Pregnant, breast-feeding, or planning a pregnancy during the study and women of childbearing potential not using adequate contraception.

Lack of suitability for the study:

• Use of prohibited therapies as specified in the respective table of the protocol.
• Acute or chronic sinusitis or non-allergic rhinitis, at the discretion of the Investigator and/or designee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A (Azelair)+Treatment B (Placebo)+Treatment C (Ryaltris), min. 14 days wash-out period; Cross-over design	Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); 2 sprays per nostril of Azelastine 0.15% twice daily. Total dose of active drug: 1644 mcg azelastine hydrochloride per day; Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; 2 sprays per nostril of Placebo twice daily.; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray; 2 sprays per nostril of Ryaltris twice daily. Total dose of active drug: 200 mcg mometasone furoate and 4800 mcg olopatadine per day
Experimental: Treatment B (Placebo)+Treatment C (Ryaltris)+Treatment A (Azelair), min. 14 days of wash-out period; Cross-over design	Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); 2 sprays per nostril of Azelastine 0.15% twice daily. Total dose of active drug: 1644 mcg azelastine hydrochloride per day; Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; 2 sprays per nostril of Placebo twice daily.; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray; 2 sprays per nostril of Ryaltris twice daily. Total dose of active drug: 200 mcg mometasone furoate and 4800 mcg olopatadine per day
Experimental: Treatment C (Ryaltris)+Treatment A (Azelair)+Treatment B (Placebo), min. 14 days of wash-out period; Cross-over design	Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); 2 sprays per nostril of Azelastine 0.15% twice daily. Total dose of active drug: 1644 mcg azelastine hydrochloride per day; Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; 2 sprays per nostril of Placebo twice daily.; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray; 2 sprays per nostril of Ryaltris twice daily. Total dose of active drug: 200 mcg mometasone furoate and 4800 mcg olopatadine per day
Experimental: Treatment A (Azelair)+Treatment C (Ryaltris)+Treatment B (Placebo), min. 14 days of wash-out period; Cross-over design	Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); 2 sprays per nostril of Azelastine 0.15% twice daily. Total dose of active drug: 1644 mcg azelastine hydrochloride per day; Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; 2 sprays per nostril of Placebo twice daily.; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray; 2 sprays per nostril of Ryaltris twice daily. Total dose of active drug: 200 mcg mometasone furoate and 4800 mcg olopatadine per day
Experimental: Treatment B (Placebo)+Treatment A (Azelair)+Treatment C (Ryaltris), min.14 days of wash-out period; Cross-over design	Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); 2 sprays per nostril of Azelastine 0.15% twice daily. Total dose of active drug: 1644 mcg azelastine hydrochloride per day; Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; 2 sprays per nostril of Placebo twice daily.; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray; 2 sprays per nostril of Ryaltris twice daily. Total dose of active drug: 200 mcg mometasone furoate and 4800 mcg olopatadine per day
Experimental: Treatment C (Ryaltris)+Treatment B (Placebo)+Treatment A (Azelair), min. 14 days of wash-out period; Cross-over design	Drug: Treatment A: Azelastine hydrochloride 0.15% nasal spray (Azelair); 2 sprays per nostril of Azelastine 0.15% twice daily. Total dose of active drug: 1644 mcg azelastine hydrochloride per day; Drug: Treatment B: Placebo (Azelastine 0.15% vehicle) nasal spray; 2 sprays per nostril of Placebo twice daily.; Drug: Treatment C: Ryaltris (Active Control) - mometasone furoate monohydrate and olopatadine hydrochloride nasal spray; 2 sprays per nostril of Ryaltris twice daily. Total dose of active drug: 200 mcg mometasone furoate and 4800 mcg olopatadine per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in TNSS at each post-dose assessment time point (0 to 4 hours after a single dose).	Onset of action of azelastine hydrochloride 0.15% nasal spray (Azelastine 0.15%) in treating the nasal symptoms of seasonal allergic rhinitis (SAR) induced by an allergen challenge in an Environmental Exposure Unit (EEU), measured by a difference from placebo in the change from baseline in patient -assessed instantaneous Total nasal symptom score (TNSS). FDA guideline defines onset of action as the first time point after initiation of treatment when the product demonstrated a greater change from baseline compared to placebo which proved durable. The TNSS is comprised of 4 symptoms from the nose, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TNSS contributes to a score ranging from 0 - 12.	0 to 4 hours post application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in TNSS at each post-dose assessment time point (0 to 4 hours after a single dose) at Visits 3, 6, and 9.	Onset of action, measured by the differences of both active treatments versus placebo in the change from baseline in patient-assessed instantaneous total symptom scores following treatment. FDA guideline defines onset of action as the first time point after initiation of treatment when the product demonstrated a greater change from baseline compared to placebo which proved durable. The TNSS is comprised of 4 symptoms from the nose, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TNSS contributes to a score ranging from 0 - 12.	0 to 4 hours post application
Changes from baseline in TOSS at each post-dose assessment time point (0 to 4 hours after a single dose) at Visits 3, 6, and 9.	Onset of action, measured by the differences of both active treatments versus placebo in the change from baseline in patient-assessed instantaneous total symptom scores following treatment. FDA guideline defines onset of action as the first time point after initiation of treatment when the product demonstrated a greater change from baseline compared to placebo which proved durable. The TOSS is comprised of 3 symptoms from the eyes, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TOSS contributes to a score ranging from 0 - 9.	0 to 4 hours post application
Changes from baseline in T7SS at each post-dose assessment time point (0 to 4 hours after a single dose) at Visits 3, 6, and 9.	Onset of action, measured by the differences of both active treatments versus placebo in the change from baseline in patient-assessed instantaneous total symptom scores following treatment. FDA guideline defines onset of action as the first time point after initiation of treatment when the product demonstrated a greater change from baseline compared to placebo which proved durable. The total 7 symptoms score (T7SS) will be the combination of the TNSS and TOSS, for a combined maximum score of 21.	0 to 4 hours post application
Change from baseline in individual symptom scores at each post-dose assessment time point (0 to 4 hours after a single dose) at Visits 3, 6, and 9.	Onset of action, measured by change from baseline in individual symptom scores at each post-dose assessment time point (0 to 4 hours after a single dose) at Visits 3, 6, and 9. Each individual symptom is scored on a scale of 0 to 3 (0 = none and 3 = severe). Secondary endpoint include pairwise treatment comparisons of both active treatments versus placebo.	0 to 4 hours post application
Changes from baseline in TNSS for all assessment time-points together.	Overall Efficacy, measured by changes from baseline in TNSS for all assessments during 0-4 hours and for visits 3, 6 and 9 together. The TNSS is comprised of 4 symptoms from the nose, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TNSS contributes to a score ranging from 0 - 12.	0 to 4 hours post application
Changes from baseline in TOSS for all assessment time-points together.	Overall Efficacy, measured by changes from baseline in TOSS for all assessments during 0-4 hours and for visits 3, 6 and 9 together. The TOSS is comprised of 3 symptoms from the eyes, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TOSS contributes to a score ranging from 0 - 9.	0 to 4 hours post application
Changes from baseline in T7SS for all assessment time-points together.	Overall Efficacy, measured by changes from baseline in T7SS for all assessments during 0-4 hours and for visits 3, 6 and 9 together. The total 7 symptoms score (T7SS) will be the combination of the TNSS and TOSS, for a combined maximum score of 21.	0 to 4 hours post application
Change from baseline in individual symptom scores for all assessment time-points together.	Overall Efficacy, measured by change from baseline in individual symptom scores for all assessments during 0-4 hours and for visits 3, 6 and 9 together. Each individual symptom is scored on a scale of 0 to 3 (0 = none and 3 = severe).	0 to 4 hours post application
Changes from baseline in TNSS for all assessment time-points together.	Overall Efficacy, measured by changes from baseline in TNSS for all assessments during 0-4 hours and for visits 4, 7 and 10 together after 3-day treatment. The TNSS is comprised of 4 symptoms from the nose, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TNSS contributes to a score ranging from 0 - 12.	0-4 hours after 3-day treatment
Changes from baseline in TOSS for all assessment time-points together.	Overall Efficacy, measured by changes from baseline in TOSS for all assessments during 0-4 hours and for visits 4, 7 and 10 together after 3-day treatment. The TOSS is comprised of 3 symptoms from the eyes, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TOSS contributes to a score ranging from 0 - 9.	0-4 hours after 3-day treatment
Changes from baseline in T7SS for all assessment time-points together.	Overall Efficacy, measured by changes from baseline in T7SS for all assessments during 0-4 hours and for visits 4, 7 and 10 together after 3-day treatment. The total 7 symptoms score (T7SS) will be the combination of the TNSS and TOSS, for a combined maximum score of 21.	0-4 hours after 3-day treatment
Change from baseline in individual symptom scores for all assessment time-points together.	Overall Efficacy, measured by change from baseline in individual symptom scores for all assessments during 0-4 hours and for visits 4, 7 and 10 together after 3-day treatment. Each individual symptom is scored on a scale of 0 to 3 (0 = none and 3 = severe).	0-4 hours after 3-day treatment

Collaborators and Investigators

• Sponsor: MEDA Pharma GmbH & Co. KG
• Investigators: Principal Investigator: Patricia Couroux, Dr., Cliantha Research

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): February 23, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: November 6, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• 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; Rhinitis, Allergic, Seasonal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Lipoxygenase Inhibitors; Mometasone Furoate; Azelastine; Olopatadine Hydrochloride
• Other Study ID Numbers: AZEL-NS-2001; C2D03217 (Other Identifier: Cliantha Research, Canada)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No