Safety and Efficacy of AL-53817 Nasal Spray Solution

Study Overview
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Brief Summary
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The purpose of this study was to determine the maximum tolerated dose of AL-53817 (Stage A) and evaluate the safety and efficacy of AL-53817 for the treatment of allergic rhinitis (Stage B).

Detailed Description
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Stage A was a 1-day, single ascending dose study utilizing 7 separate cohorts of unique subjects (healthy normal volunteers). Each cohort was administered a different dose of AL-53817 Nasal Spray Solution in order to determine the maximum tolerated dose (MTD). In Stage B, 2 different cohorts of unique, ragweed-sensitive subjects were administered the MTD for up to 5 days twice a day to determine the safety and efficacy of AL-53817 Nasal Spray Solution for the treatment of allergic rhinitis. Subjects were required to meet minimum allergic rhinitis scores at two qualifying EEC visits to participate in the study. Subjects were continually housed in clinic during the 5-day treatment period.

Official Title
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Safety and Efficacy of AL-53817 Nasal Spray Solution in Ragweed Sensitive Subjects in an Environmental Exposure Chamber (EEC)

Conditions
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Nasal Allergies, Allergies

Intervention / Treatment
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* Drug: AL-53817 nasal spray solution
* Other: Vehicle nasal spray


Participation Criteria
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Eligibility Criteria
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Stage A Inclusion Criteria: Willing and able to give written informed consent. In good health in the opinion of an appropriately qualified physician. Females of childbearing potential (who are not at least 1 year post-menopausal or surgically sterilized) must have a negative urine pregnancy test at Visit 1, and must not be nursing or plan to become pregnant during the course of the study. Other protocol-defined inclusion criteria may apply. Stage B Inclusion Criteria: History of non-recalcitrant seasonal allergic rhinitis during the fall allergy season. Allergy to short ragweed allergen, defined by positive skin prick test for short ragweed allergen within the 12 months prior to Visit 1. Be in good health in the opinion of an appropriately qualified physician. Females of childbearing potential (who are not at least 1 year post-menopausal or surgically sterilized) must have negative urine pregnancy test at Visit 1, and must not be nursing or plan to become pregnant during the course of the study. Other protocol-defined inclusion criteria may apply. Stage A Exclusion Criteria: Hypersensitivity to the study drug or any component of the test articles, including benzalkonium chloride. Using any prescription or non-prescription systemic or topical medications, vitamins or dietary supplements within 14 days prior to the check-in day (except for acetaminophen at doses of < 2 grams/day or topical, hormonal-oral, implantable or injectable contraceptives). Current or recent history of severe, unstable, or uncontrolled conditions based upon a review of medical history and/or physical examination. Any nasal disorder that could preclude safe administration of study medication and/or interfere with the evaluation of the study medication. History of HIV, hepatitis B or active hepatitis A as determined by medical history and/or by serology at the Screening Visit. Any screening clinical laboratory result (hematology, serum chemistry or urinalysis) outside the normal range that is clinically relevant in the opinion of an appropriately qualified physician and/or Alcon physician. Participation in any investigational study within 30 days of entry into this study or concomitantly with this study. Other protocol-defined exclusion criteria may apply. Stage B Exclusion Criteria: Any screening clinical laboratory result (hematology, serum chemistry or urinalysis) outside the normal range that is clinically relevant in the opinion of an appropriately qualified physician and/or Alcon physician. Using any prescription or non-prescription systemic or topical medications, vitamins or dietary supplements within 14 days prior to the check-in day (except for acetaminophen at doses of < 2 grams/day or topical, hormonal-oral, implantable or injectable contraceptives). History of HIV, hepatitis B or C or active hepatitis A as determined by medical history and/or by serology at the Screening Visit. Any nasal disorder that could preclude safe administration of study medication and/or interfere with the evaluation of the study medication. Confirmed diagnosis of chronic rhinosinusitis within 12 months of Visit. Confirmed diagnosis of severe rhinitis or rhinosinusitis prior to Visit 1 that, in the opinion of the Investigator, would preclude safe subject participation in the study. Current or recent history of any severe, unstable, or uncontrolled condition that, in the opinion of the Investigator, would preclude safe participation in the study. Participation in any investigational study within 30 days of entry into this study or concomitantly with this study. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage B/AL-53817<br>Stage B: AL-53817 nasal spray solution, 1 spray to each nostril twice a day for 4 days. On Day 5, 1 spray to each nostril 60 minutes before entering the EEC. | Drug: AL-53817 nasal spray solution<br>* Active ingredients administered in 1 of 3 concentrations during Stage A to determine maximum tolerated dose (MTD), and administered at maximum tolerated dose during Stage B.<br>|
| Placebo Comparator: Stage B/Vehicle<br>Stage B: Vehicle nasal spray, 1 spray to each nostril twice a day for 4 days. On Day 5, 1 spray to each nostril 60 minutes before entering the EEC. | Other: Vehicle nasal spray<br>* Inactive ingredients used as placebo comparator during Stage A and Stage B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events in Stage A | Adverse events, including serious adverse events and deaths, were reported regardless of test article relationship. | Day 1 | 
| Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | Stage B: Nasal congestion was assessed by the subject before entering the EEC and at 14 timepoints over a 6-hour period after entering the EEC. Nasal congestion was scored on a scale from 0-3, where 0=none and 3=severe. Baseline EEC was conducted up to 21 days prior to the 5-day treatment period. | Baseline (pretreatment), Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | Stage B: Nasal symptoms were assessed by the subject before entering the EEC and at 14 timepoints over a 6-hour period after entering the EEC. TNSS score (0-12) was a sum of scores for nasal congestion, sneezing, itchy nose, and runny nose scores, each individually assessed on a 0 to 3 scale, where 0=none and 3=severe. Baseline EEC was conducted up to 21 days prior to the 5-day treatment period. | Baseline (pretreatment), Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EEC, Healthy subjects, Nasal allergies, Allergies, Environmental Exposure Chamber, Ragweed