Clinical trial NCT06019000: Study of CYR-064 Versus Placebo in Patients.
Official title: A Randomized, Double-Blinded, Placebo-Controlled Trial to Determine The Safety and Efficacy of CYR-064
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hyposmia
Keywords: post viral smell loss
Lead sponsor: Cyrano Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-31
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

Brief summary: Randomized, double-blinded, placebo-controlled trial to determine the safety and efficacy of CYR-064.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Able to provide written informed consent.
* Male or female 18-70 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.

Primary outcomes:
measure: Primary Outcome - Safety and Tolerability
timeFrame: Approximately 32 weeks
Secondary outcomes:
measure: Secondary Outcome-improvement on NRS-11 Smell-PRO
timeFrame: Approximately 24 weeks
measure: Secondary Outcome-improvement on NRS-11 Taste-PRO
timeFrame: Approximately 24 weeks
measure: Secondary Outcome-Mean Change in NRS-11 Smell-PRO
timeFrame: Approximately 24 weeks
measure: Secondary Outcome-Mean Change in NRS-11 Taste-PRO
timeFrame: Approximately 24 weeks
measure: Change in Visual Rating Scale (VRS) scores
timeFrame: Approximately 24 weeks
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Colorado ENT & Allergy
state: Colorado
city: Boca Raton
country: United States
facility: ENTAAFL
state: Florida
city: Plantation
country: United States
facility: ENTAAFL
state: Florida
city: Port Saint Lucie
country: United States
facility: ENTAAFL
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: KU Medical Center-University of Kansas
state: Kansas
city: Louisville
country: United States
facility: Advanced ENT and Allergy
state: Kentucky
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Centers for Advanced ENT
state: Maryland
city: Bethlehem
country: United States
facility: Specialty Physician Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina-MUSC
state: South Carolina
city: North Charleston
country: United States
facility: Charleston ENT and Allergy
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Puyallup
country: United States
facility: Ear Nose Throat & Allergy Associates
state: Washington
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Mas Takashima, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: a review of clinical and biochemical evaluations of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013 Sep-Oct;34(5):477-89. doi: 10.1016/j.amjoto.2013.04.006. Epub 2013 Jun 2.
citation: Henkin RI. Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. Ther Drug Monit. 2012 Apr;34(2):217-21. doi: 10.1097/FTD.0b013e3182492a20.
citation: Henkin RI. Growth Factors in Olfaction. In: Preedy VR, editor. Handbook of Growth and Growth Monitoring in Health and Disease. New York, NY: Springer New York; 2012. p. 1417-36.
citation: Henkin RI, Abdelmeguid M. Improved Smell and Taste Dysfunction with Intranasal Theophylline. Am J Otolaryngol Head Neck Surg. 2019;2(9):1070.
citation: Henkin RI, Hosein S, Stateman WA, Knoppel AB, Abdelmeguid M. Improved smell function with increased nasal mucus sonic hedgehog in hyposmic patients after treatment with oral theophylline. Am J Otolaryngol. 2017 Mar-Apr;38(2):143-147. doi: 10.1016/j.amjoto.2016.11.010. Epub 2016 Nov 23.
citation: Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg. 2012 Nov;138(11):1064-70. doi: 10.1001/2013.jamaoto.342.
citation: Henkin RI, Velicu I. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction. Clin Invest Med. 2008;31(2):E78-84. doi: 10.25011/cim.v31i2.3367.
citation: Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.
citation: Henkin RI, Velicu I, Schmidt L. Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides. Am J Med Sci. 2011 Jan;341(1):17-22. doi: 10.1097/MAJ.0b013e3181f1fdc8.