Chronic Sinusitis, Chronic Rhinosinusitis (Diagnosis)
Conditions
Brief summary
Multicenter, phase III, randomized, blinded, controlled, parallel group with safety extension phase with crossover or continued treatment.
Detailed description
This is a 52-week, multicenter, phase III, randomized, blinded, controlled, parallel group with a 24-week treatment period followed by a safety extension phase with crossover or continued treatment 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 * Undergone at least 2 trials of medical treatments in the past * Mean 3 cardinal symptom (3CS) score * Bilateral ethmoid disease confirmed on CT * Has been informed of the nature of the study and provided written informed consent * Agrees to comply with all study requirements * If on a waiting list for sinonasal surgery, willing to be removed from list or have surgery date cancelled for the duration of the study.
Exclusion criteria
* Inability to tolerate topical anesthesia or endoscopic procedure * 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. | 24 Weeks | 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/each question 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/each question 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 | The percent opacification of the bilateral anterior and posterior ethmoids will be assessed by 3-D volumetric CT analysis at baseline and Week 20. A negative change from Baseline indicates improvement from Baseline. |
| Participants With Rescue Treatments for CRS Through Week 24 | Week 24 | This endpoint is descriptively summarized per the prespecified plan. This includes participants that used systemic corticosteroid for any reason as well as participants that were recommended/underwent sinonasal surgery. |
Countries
Austria, Czechia, Poland, Spain, United States
Participant flow
Recruitment details
Week 24 Treatment Period: 2:1 (LYR-210 to Sham) Randomization; Safety Extension Period: Sham participants received LYR-210; LYR-210 participants received LYR-210 or Sham (1:1)
Participants by arm
| Arm | Count |
|---|---|
| LYR-210 Single administration of LYR-210 drug matrix (7500 μg)
LYR-210: LYR-210 drug matrix (mometasone furoate)
Background Therapy: Daily Saline Irrigation | 124 |
| Sham Procedure Control Single mock administration procedure
Sham procedure control: Sham procedure control
Background Therapy: Daily Saline Irrigation | 66 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Safety Extension Period | Adverse Event | 0 | 0 | 2 | 1 | 1 |
| Safety Extension Period | Bilateral dislodgement | 0 | 0 | 4 | 0 | 1 |
| Safety Extension Period | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Safety Extension Period | Treatment administration failure | 0 | 0 | 0 | 1 | 4 |
| Safety Extension Period | Withdrawal by Subject | 0 | 0 | 2 | 0 | 4 |
| Week 24 Treatment Period | Adverse Event | 3 | 0 | 0 | 0 | 0 |
| Week 24 Treatment Period | Bilateral dislodgement | 13 | 0 | 0 | 0 | 0 |
| Week 24 Treatment Period | Other, not specified | 3 | 0 | 0 | 0 | 0 |
| Week 24 Treatment Period | Physician Decision | 0 | 1 | 0 | 0 | 0 |
| Week 24 Treatment Period | Treatment administration failure/procedure not attempted | 6 | 0 | 0 | 0 | 0 |
| Week 24 Treatment Period | Withdrawal by Subject | 2 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | LYR-210 | Total | Sham Procedure Control |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 25 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 165 Participants | 58 Participants |
| Age, Continuous | 50 years STANDARD_DEVIATION 13.65 | 48 years STANDARD_DEVIATION 14.06 | 45 years STANDARD_DEVIATION 14.42 |
| BMI | 27.9 kg/m² STANDARD_DEVIATION 5.63 | 27.7 kg/m² STANDARD_DEVIATION 5.39 | 27.4 kg/m² STANDARD_DEVIATION 4.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 22 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 168 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 111 Participants | 165 Participants | 54 Participants |
| Region of Enrollment Austria | 3 Participants | 4 Participants | 1 Participants |
| Region of Enrollment Czechia | 9 Participants | 10 Participants | 1 Participants |
| Region of Enrollment Poland | 28 Participants | 48 Participants | 20 Participants |
| Region of Enrollment Spain | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment United States | 80 Participants | 122 Participants | 42 Participants |
| Sex: Female, Male Female | 53 Participants | 84 Participants | 31 Participants |
| Sex: Female, Male Male | 71 Participants | 106 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 124 | 0 / 66 | 0 / 42 | 0 / 41 | 0 / 48 |
| other Total, other adverse events | 78 / 124 | 26 / 66 | 21 / 42 | 9 / 41 | 19 / 48 |
| serious Total, serious adverse events | 4 / 124 | 4 / 66 | 2 / 42 | 3 / 41 | 3 / 48 |
Outcome results
Primary
Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps.
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/each question 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.
Time frame: 24 Weeks
Population: ITT Analysis Set Without Nasal Polyps
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 | Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps. | -2.13 score on a scale | Standard Deviation 2.172 |
| Sham Procedure Control | Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps. | -2.06 score on a scale | Standard Deviation 2.136 |
Secondary
CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at 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.
Time frame: Week 24
Population: ITT Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 | CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24 | -19.7 score on a scale | Standard Deviation 21.67 |
| Sham Procedure Control | CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24 | -15.7 score on a scale | Standard Deviation 18.55 |
Secondary
CFBL in the 3-D Volumetric CT Score at Week 20
The percent opacification of the bilateral anterior and posterior ethmoids will be assessed by 3-D volumetric CT analysis at baseline and Week 20. A negative change from Baseline indicates improvement from Baseline.
Time frame: Week 20
Population: ITT Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 | CFBL in the 3-D Volumetric CT Score at Week 20 | -2.705 Percent ethmoid opacification | Standard Deviation 10.932 |
| Sham Procedure Control | CFBL in the 3-D Volumetric CT Score at Week 20 | -0.279 Percent ethmoid opacification | Standard Deviation 9.9706 |
Secondary
CFBL in the 7-day Average Composite Score of 3CS in All Participants at 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/each question 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.
Time frame: Week 24
Population: ITT Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 | CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24. | -2.35 score on a scale | Standard Deviation 2.278 |
| Sham Procedure Control | CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24. | -1.83 score on a scale | Standard Deviation 2.104 |
Secondary
Participants With Rescue Treatments for CRS Through Week 24
This endpoint is descriptively summarized per the prespecified plan. This includes participants that used systemic corticosteroid for any reason as well as participants that were recommended/underwent sinonasal surgery.
Time frame: Week 24
Population: ITT Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LYR-210 | Participants With Rescue Treatments for CRS Through Week 24 | 12 Participants |
| Sham Procedure Control | Participants With Rescue Treatments for CRS Through Week 24 | 7 Participants |