CYR-064 for Loss of Smell

Not currently recruiting at 14 trial locations

Overseen By Mas Takashima, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cyrano Therapeutics, Inc.

Must not be taking: Intranasal medications

Disqualifiers: Brain injury, Parkinson's, Alzheimer's, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CYR-064 (a form of theophylline) to determine its safety and effectiveness for people who have lost their sense of smell. Participants will receive either CYR-064 or a placebo (a non-active substance) as a nasal solution for 24 weeks. The goal is to compare the effectiveness of CYR-064 to the placebo. Suitable candidates for this trial are those who have difficulty smelling, have no structural issues in their nasal cavity, and are willing to self-administer the treatment. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop using any over-the-counter or prescription medications administered intranasally, except for nasal saline. Other medications may need to be stopped if the investigator believes they could affect safety or compliance with the study.

Is there any evidence suggesting that CYR-064 is likely to be safe for humans?

Research shows that CYR-064, a nasal spray, is being tested to improve the sense of smell. In earlier studies, participants used CYR-064 for 24 weeks to assess its safety and effectiveness. Although data remains limited, ongoing studies aim to learn more about how well participants tolerate the treatment.

Since the current trial is in Phase 2, earlier trials have provided some evidence of its safety. This suggests the treatment is likely well-tolerated, but more information is needed to fully understand any possible side effects. Remember, CYR-064 is still under investigation, so it is important to consider that research is ongoing when evaluating safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for loss of smell?

Most treatments for loss of smell typically involve steroids or olfactory training. CYR-064 stands out because it is delivered as a nasal solution, allowing for direct application to the nasal passages, which could enhance its effectiveness. Researchers are excited about CYR-064 because it targets the underlying issues more directly than systemic treatments, potentially leading to quicker and more effective recovery of the sense of smell. Additionally, CYR-064 is self-administered, offering convenience and ease of use for patients.

What evidence suggests that CYR-064 might be an effective treatment for loss of smell?

Research shows that CYR-064 may help improve the sense of smell. In this trial, participants will receive either a nasal solution of CYR-064 at one of two doses or a placebo. Previous studies found that people using CYR-064 reported better smell scores than those using a placebo. This nasal spray is being tested to help those who have lost their sense of smell, especially after viral infections. Some early results suggest that CYR-064 might also help restore taste. As research continues, more will be learned about its effectiveness and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Mas Takashima, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 who've lost their sense of smell but don't have any nasal blockages or diseases causing it. They must be able to take the study drug themselves and follow the trial's procedures.

Inclusion Criteria

Endoscopy of the nasal cavity reveals no structural or pathologic issues that would impede delivery of study drug to olfactory receptors, as concluded by the Investigator.

I can take the study drug as directed and follow the study's schedule.

You have had a CT scan of your nose within the past two years with no identifiable structural or pathologic issue that would prevent study drug from reaching olfactory receptors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either CYR-064 or placebo nasal solution twice a day for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• CYR-064

Trial Overview

The trial tests CYR-064 against a placebo to see if it's safe and works for people with reduced sense of smell. Participants are randomly chosen to receive either CYR-064 or a fake drug, without knowing which one they get.

How Is the Trial Designed?

Group I: CYR-064 dose 2 Experimental Treatment 1 Intervention

Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.

Group II: CYR-064 dose 1 Active Control 1 Intervention

Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.

Group III: Placebo Placebo Group 1 Intervention

Treatment with Placebo nasal solution for 24 weeks. CYR-064 will be self-administered by patients.

Who Is Running the Clinical Trial?

Cyrano Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

150+

Published Research Related to This Trial

Theophylline, an oral medication used to treat hyposmia, was found in nasal mucus after administration, indicating it can effectively reach the nasal area where it may help correct smell loss.

In a study involving 23 hyposmic patients, the levels of theophylline in nasal mucus were found to be 74% of those in serum and 111% compared to saliva, suggesting that nasal mucus can be a reliable, noninvasive way to monitor theophylline levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. Henkin, RI.[2013]

In a study of 2,766 medical inpatients, 10.8% experienced adverse reactions to theophylline, with gastrointestinal issues being the most common (7.8%).

Higher doses of theophylline were linked to more adverse effects, while current cigarette smoking appeared to reduce the frequency of these reactions, particularly in younger patients with normal kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toxocity of theophylline in relation to cigarette smoking. A report from the Boston Collaborative Drug Surveillance Program. Pfeifer, HJ., Greenblatt, DJ.[2019]

In a study involving 22 adults with post-viral olfactory dysfunction, intranasal theophylline saline irrigation was found to be safe, with no adverse events reported and undetectable serum theophylline levels in most patients.

While slightly more patients in the theophylline group reported improved smell compared to placebo, the differences were not clinically meaningful, indicating that larger trials or dose adjustments may be necessary to achieve significant treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction. Lee, JJ., Peterson, AM., Kallogjeri, D., et al.[2023]

In a study of 312 patients with smell loss (hyposmia), theophylline treatment led to significant improvements in smell function, with 50.3% of patients reporting subjective improvement and 21.7% achieving normal smell function.

Higher doses of theophylline (600-800 mg) were more effective than lower doses, and improvements in smell function persisted as long as treatment was maintained, with follow-up periods ranging from 6 to 72 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label controlled trial of theophylline for treatment of patients with hyposmia. Henkin, RI., Velicu, I., Schmidt, L.[2013]

In a randomized crossover study involving 12 elderly patients with chronic airflow obstruction, Uniphyl tablets (a once-daily theophylline preparation) significantly improved peak expiratory flow rates compared to Theo-Dur tablets and placebo, indicating better efficacy in managing airflow obstruction.

Despite observing cardiac ectopy in most patients, there was no significant increase in ectopic activity during the theophylline treatments compared to placebo, suggesting that Uniphyl tablets may be safe for use in this population without exacerbating cardiac issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-daily Uniphyl tablets compared with twice-daily Theo-Dur tablets in elderly patients with chronic airflow obstruction. Rivington, RN., Calcutt, L., Hodder, RV., et al.[2019]

In a pilot study involving 10 patients with hyposmia and hypogeusia, intranasal theophylline methylpropyl paraben was found to be more effective than oral theophylline in improving taste and smell acuity, with 8 out of 10 patients showing improvement after just 4 weeks of treatment.

Intranasal theophylline treatment was also associated with no adverse effects and resulted in a greater increase in body weight compared to oral administration, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Henkin, RI., Schultz, M., Minnick-Poppe, L.[2012]

In a study of 312 patients with hyposmia, oral treatment with theophylline improved smell function in over 50% of participants, indicating its potential efficacy as a treatment for smell disorders.

Responders to theophylline treatment had higher levels of nasal mucus cAMP and cGMP compared to nonresponders, suggesting that these biomarkers may help predict which patients are more likely to benefit from theophylline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides. Henkin, RI., Velicu, I., Schmidt, L.[2018]

Theophylline, an unspecific phosphodiesterase inhibitor, appears to be taken up by the olfactory epithelium in mice and may interact with olfactory signal transduction, as indicated by changes in electro-olfactogram (EOG) responses.

Administration of theophylline led to a significant decrease in EOG amplitudes during olfactory stimulation, suggesting it may negatively impact olfactory sensitivity rather than enhance it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theophylline induces changes in the electro-olfactogram of the mouse. Gudziol, V., Pietsch, J., Witt, M., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06498687?cond=hyposmia&rank=4

Theophylline Nasal Spray for PD-Related Hyposmia and ...

The study drug of CYR-064, self-administered for a 24-week Treatment Period, is intended to improve the sense of smell in participants with persistent hyposmia ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06019000

Study of CYR-064 Versus Placebo in Patients.

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.

3.

neurologylive.com

neurologylive.com/view/new-investigator-initiated-study-test-cyr-064-for-hyposmia-parkinsons

New Investigator-Initiated Study to Test CYR-064 for ...

Outcome measures include changes in smell and taste perception, with safety and efficacy ... loss of smell and the associated loss of taste ...

4.

houstonmethodist.org

houstonmethodist.org/leading-medicine-blog/articles/2024/aug/houston-methodist-researchers-lead-first-of-its-kind-phase-2-trial-for-hyposmia/

Houston Methodist Researchers Lead First-of-its-Kind ...

"CYR-064 has the potential to become the first pharmaceutical product to restore the senses of smell and taste in patients with post-viral ...

5.

cyranotherapeutics.com

cyranotherapeutics.com/clinical/

Loss of Smell Research: Enroll in a Clinical Trial ...

This loss of smell research aims to address the limited treatment options for smell disorders by generating valuable data on CYR-064's safety and effectiveness.

6.

clinicaltrialvanguard.com

clinicaltrialvanguard.com/executiveinterviews/first-pharma-to-restore-sense-of-smell-inside-the-flavor-trial-quest-to-treat-postviral-olfactory-loss/

First Pharma to Restore Sense of Smell? Inside the ...

We delve into how the team designed endpoints that matter to patients and regulators, the biology behind CYR-064, safeguards against placebo and ...