Chronic Sinusitis, Chronic Rhinosinusitis (Diagnosis)
Conditions
Brief summary
Multicenter, phase III, randomized, blinded, controlled, parallel group.
Detailed description
This is a 24-week, multicenter, phase III, randomized, blinded, controlled, parallel group with a 24-week treatment period to evaluate the efficacy and safety of LYR-210 compared with sham control for treatment in adults with CRS.
Interventions
DRUGLYR-210
LYR-210 drug matrix (mometasone furoate)
Sham procedure control
OTHERBackground therapy
Daily Saline Irrigation
Sponsors
Lyra Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 * Diagnosed as having CRS * Bilateral ethmoid disease confirmed on CT * Mean 3 cardinal symptom (3CS) score * Undergone at least 2 trials of medical treatments in the past * Has been informed of the nature of the study and provided written informed consent * Agrees to comply with all study requirements * If currently on a waiting list for sinonasal surgery, willing to be removed from the waiting list or have preplanned surgery date cancelled for the duration of the study. \[Note: this does not preclude a participant from receiving or being recommended for sinonasal surgery as rescue treatment during the study\].
Exclusion criteria
* Inability to tolerate topical anesthesia * Previous nasal surgery * Presence of nasal polyp grade 2 or higher * Seasonal allergic rhinitis * Perennial rhinitis with symptoms that are well controlled by regular use of intranasal corticosteroids * Severe asthma * History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, atrophic rhinitis, or odontogenic sinusitis * Obstruction preventing proper placement and retention of LYR-210 as seen on endoscopy * Anatomic variation that, in the opinion of the investigator, would adversely impact placement of LYR-210 as seen on CT * Known history of hypersensitivity or intolerance to corticosteroids * Known history of hypothalamic pituitary adrenal axial dysfunction * Previous pituitary or adrenal surgery * Dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. * Past or present acute or chronic intracranial or orbital complications of CRS * History or diagnosis (in either eye) of glaucoma or ocular hypertension * Past or present functional vision in only 1 eye * Past, present, or planned organ transplant or chemotherapy with immunosuppression * Currently positive for COVID-19 or residual sinonasal symptoms from a previous COVID-19 infection * Pregnant or breast feeding. Females of child-bearing potential must test negative for pregnancy at the time of screening * Evidence of disease or condition expected to compromise survival or ability to complete follow-up assessments * Currently participating in an investigational drug or device study * Determined by the investigator as not suitable to be enrolled
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps | Week 24 | The 3CS are nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure. The diary is completed daily by study participants throughout the study. Each symptom is rated on a 4-point (0-3) scale where 0= none/absent symptoms, 1=mild symptoms, 2=moderate symptoms, and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24 | Week 24 | The 3CS are nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure. The diary is completed daily by study participants throughout the study. Each symptom is rated on a 4-point (0-3) scale where 0= none/absent symptoms, 1=mild symptoms, 2=moderate symptoms, and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms. |
| CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24 | Week 24 | The SNOT-22 questionnaire is a 22-item disease-specific quality of life instrument. Each symptom is scored on a 6-point scale where 0 = no problem and 5 = problem as bad as it can be. The total SNOT-22 score is the sum of the 22 items and can range from 0 to 110 with higher scores indicating worse symptoms. |
| CFBL in the 3-D Volumetric CT Score at Week 20 | Week 20 | Change from baseline in the percent opacification of the bilateral anterior and posterior ethmoids at Week 20, as determined by 3-D volumetric CT analysis. 3-D volumetric scoring involves evaluations of each slice of 3-D coronal CT sequences and summing of all the slices to create a volumetric score ranging from 0% to 100%. A negative change from Baseline indicates improvement from Baseline. |
| Rescue Treatment Requirement Through Week 24 | Week 24 | Number and percent of participants requiring rescue treatment (systemic corticosteroid for any reason or participants that were recommended/underwent sinonasal surgery) through Week 24. |
Countries
Belgium, Bulgaria, Germany, Hungary, Poland, United States
Participant flow
Recruitment details
Week 24 Treatment Period: 2:1 (LYR-210 to Sham) Randomization
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 146 Participants |
| Age, Continuous | 50 Years STANDARD_DEVIATION 14.65 |
| Baseline 3CS Score | 6.46 Score STANDARD_DEVIATION 1.337 |
| Baseline SNOT-22 Total Score | 56.2 Score STANDARD_DEVIATION 17.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 145 Participants |
| Region of Enrollment Belgium | 2 Participants |
| Region of Enrollment Bulgaria | 21 Participants |
| Region of Enrollment Germany | 26 Participants |
| Region of Enrollment Hungary | 17 Participants |
| Region of Enrollment Poland | 12 Participants |
| Region of Enrollment United States | 94 Participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 60 |
| other Total, other adverse events | 48 / 112 | 17 / 60 |
| serious Total, serious adverse events | 2 / 112 | 0 / 60 |
Outcome results
None listed