Study of CYR-064 Versus Placebo in Patients.

Study Overview
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Brief Summary
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Randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of CYR-064.

Detailed Description
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The purpose of this study is to determine the safety and effectiveness of CYR-064 in a randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of CYR064. The study will take approximately 32 weeks which will include a 4-week screening period to evaluate if participants are right for the Study, followed by a 24-week Treatment Period, and a 1 week follow up after participants have completed the Study. About 150 subjects will participate in this study in about 25 research sites in the United States.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled Trial to Determine The Safety and Efficacy of CYR-064

Conditions
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Hyposmia

Intervention / Treatment
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* Combination Product: CYR-064


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent. Male or female 18-65 years of age. Endoscopy of the nasal cavity showing no structural or pathologic issues leading to hyposmia (nasal polyps, sinusitis, infection, etc.) that in the opinion of the Investigator, believes would hinder the delivery of study drug to the olfactory receptors. CT scan of the nasal cavity after the onset of hyposmia (within prior 2 years) prior to Baseline showing no structural or pathologic issue leading to hyposmia that in the opinion of the Investigator, believes would hinder the delivery of study drug to the olfactory receptors. Willing and able to self-administer the study drug, follow the study drug administration instructions, comply with study procedures, and participate in the scheduled study visits specified in this protocol. Exclusion Criteria: History of traumatic brain injury, Parkinson's disease, early dementia, Alzheimer's disease, or any other condition in which hyposmia is not expected to improve in the opinion of the Investigator, such as history of congenital or idiopathic hyposmia or a surgical procedure that led to hyposmia. History of surgery that led to hyposmia. Concomitant Medical Conditions Current symptoms or signs of an acute respiratory viral illness at Screening or Baseline. Chronic viral infection or immunodeficiency condition (e.g., medical history of human immunodeficiency virus) based on medical records. Any active malignancy. Any concomitant medical condition that in the opinion of the Investigator, compromises patient safety or compliance with the study protocol or collected data. History of moderate to severe Substance Use Disorder within the past 3 years as assessed by the Investigator. History of persistent chronic sinusitis without polyps or chronic sinusitis with polyps. Use or planned use of tobacco or nicotine-containing products, including smoking, smokeless tobacco, e-cigarettes, or nicotine replacement products within 3 months prior to Screening through EOS. Unwilling or unable to discontinue current or planned use of over the counter or prescription medication administered intranasally, with the exception of nasal saline. Use or planned use of another investigational drug within 4 weeks prior to Screening through Follow-Up. Receiving any concomitant medication/therapy that would, in the opinion of the Investigator, compromise patient safety or compliance with the study protocol or collected data. General Exclusions Any female who is pregnant, planning to become pregnant during the study, or who is lactating. Vulnerable patients. Any condition or abnormality (including clinical laboratory, physical examination, or vital sign abnormalities), current or past, that, in the opinion of the Investigator, would compromise the efficacy evaluation, safety of the patient, or would interfere with or complicate study procedures or assessments.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: The study treatment of CYR-064 is administered for a 24-week Treatment Period. Patients who meet all study criteria and have consented to participation will be randomized (1:1:1) to three parallel study arms, with two different dose strengths and a placebo group over 24 weeks. CYR-064 dose 1 CYR-064 dose 2 Placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CYR-064 dose 1<br>Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients. | Combination Product: CYR-064<br>* CYR-064 is a nasal solution.<br>|
| Experimental: CYR-064 dose 2<br>Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients. | Combination Product: CYR-064<br>* CYR-064 is a nasal solution.<br>|
| Placebo Comparator: Placebo<br>Treatment with Placebo nasal solution for 24 weeks. CYR-064 will be self-administered by patients. | Combination Product: CYR-064<br>* CYR-064 is a nasal solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome - Safety and Tolerability | The count and percentage of patients reporting AEs, SAEs, and SUSARs will be summarized overall, by System Organ Class, Preferred Term within the System Organ Class, maximum severity, and relationship to study drug. All other safety parameters, including clinical laboratory values through blood draws, will be summarized using descriptive statistics for continuous variables and counts and percentages for categorical variables. All changes in nasal mucosal appearance will be noted. | Approximately 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome-improvement on NRS-11 Smell-PRO | Improvement in patient reported NRS-11 Smell-PRO (scale of 0-10) in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24. | Approximately 24 weeks | 
| Secondary Outcome-improvement on NRS-11 Taste-PRO | Improvement in patient reported NRS-11 Taste-PRO (scale of 0-10) in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24. | Approximately 24 weeks | 
| Secondary Outcome-Mean Change in NRS-11 Smell-PRO | Mean Change in NRS-11 Smell-PRO from Baseline to Week 24 between CYR-064 low and high dose and placebo from Baseline to Week 24 | Approximately 24 weeks | 
| Secondary Outcome-Mean Change in NRS-11 Taste-PRO | Mean Change in NRS-11 Taste-PRO from Baseline to Week 24 between CYR-064 low and high dose and placebo from Baseline to Week 2 | Approximately 24 weeks | 
| Change in Visual Rating Scale (VRS) scores | Change in Visual Rating Scale (VRS) scores in CYR-064 low dose and high dose groups as compared with placebo from Baseline to Week 24. VRS high dose versus placebo VRS low dose versus placebo VRS low and high dose combined versus placebo | Approximately 24 weeks |