Chronic Sinusitis, Chronic Rhinosinusitis (Diagnosis)
Conditions
Brief summary
This is a Phase II, Randomized, Blinded, Sham Procedure-Controlled, Parallel-Group Trial to Evaluate the Efficacy, Safety and Tolerability of LYR-210 in Adult Subjects with Chronic Sinusitis.
Detailed description
LYR-210 is a drug depot, which contains the anti-inflammatory medication mometasone furoate (MF) pre-loaded in a single use applicator. LYR-210 is intended to be placed bilaterally into the sino-nasal passages by an otolaryngologist. Once in place, each LYR-210 drug depot is designed to gradually deliver sustained topical doses of MF to the inflamed mucosal sinus tissue over 24 weeks.
Interventions
DRUGLYR-210
A single administration of LYR-210 depot
OTHERSham comparator
Sham comparator
Sponsors
Lyra Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CS. * Two trials of medical treatments for CS in the past. * Minimum CS symptom score. * Ability to tolerate topical anesthesia. * Has been informed of the nature of the study and has provided written informed consent as approved by the Institutional Review Board (IRB)/Ethics Committee (EC) of the respective clinical site. * Agrees to comply with all study requirements.
Exclusion criteria
* Have undergone previous sinus surgery. * Pregnant or breast feeding. * Known history of hypersensitivity or intolerance to corticosteroids. * History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, or atrophic rhinitis. * Known history of hypothalamic pituitary adrenal axial dysfunction or having a morning serum cortisol level at screening outside of the normal range. * Had dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. * Past or present functional vision in only one eye. * Has cataracts * Past, present, or planned organ transplant or chemotherapy with immunosuppression. * Currently participating in an investigational drug or device study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (CFBL) in Chronic Sinusitis Symptom Scores at Week 4 | Week 4 | Participants score their CS symptoms on a 4-point scale as follows: 0 = absent symptoms (no sign/symptom evident), 1 = mild symptoms (sign/symptom present but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable), 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping). The scores are summed and averaged over the proceeding 7 days; higher scores indicate higher severity of symptoms of CS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CFBL in Chronic Sinusitis Symptom Scores at Week 24 | Week 24 | Participants score their CS symptoms on a 4-point scale as follows: 0 = absent symptoms (no sign/symptom evident), 1 = mild symptoms (sign/symptom present but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable), 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping). The scores are summed and averaged over the proceeding 7 days; higher scores indicate higher severity of symptoms of CS. |
| Participants With Improved Bilateral Zinreich Score at Week 24 | Week 24 | Each sinus is assigned a score based on the percentage of opacification as follows: 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76 % to 99%, 5 = 100% or completely occluded. Each sinus pair has a bilateral score in the range of 0 to 10. Higher scores indicate higher severity of sinus opacification. Responder is defined as a participant with at least a 1-point decrease in the imaging score at Week 24 compared with baseline. |
| Change From Baseline in the 22-item Sino-nasal Outcome Test (SNOT-22) Total Score at Week 24 | 24 weeks | Participants score the severity of their symptoms and social/emotional consequences of CS on a 6-point scale: 0 = no problem, 1 = very mild problem, 2 = mild or slight problem, 3 = moderate problem, 4 = severe problem, 5 = problem as bad as it can be. The scores are summed in the range of 0-110; higher scores indicate higher severity of symptoms or social/emotional consequences of CS. |
| Plasma Drug Concentrations of MF at Week 4 | 4 Weeks | To evaluate the pharmacokinetics of LYR-210 |
| Plasma Drug Concentrations of MF at Week 12 | 12 weeks | To evaluate the pharmacokinetics of LYR-210 |
| The Number of Participants With Treatment-related Adverse Events for up to 24 Weeks | 24 weeks | To evaluate the safety and tolerability of LYR-210 |
Countries
Australia, Austria, Czechia, New Zealand, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LYR-210 (Low Dose) In-office bilateral placement of the LYR-210 drug depot (mometasone furoate low dose) in the middle meatus
LYR-210: A single administration of LYR-210 depot | 23 |
| LYR-210 (High Dose) In-office bilateral placement of the LYR-210 drug depot (mometasone furoate high dose) in the middle meatus
LYR-210: A single administration of LYR-210 depot | 21 |
| Sham Procedure In-office bilateral sham procedure
Sham comparator: Sham comparator | 23 |
| Total | 67 |
Baseline characteristics
| Characteristic | LYR-210 (Low Dose) | LYR-210 (High Dose) | Sham Procedure | Total |
|---|---|---|---|---|
| Age, Continuous | 42.3 Years STANDARD_DEVIATION 12.72 | 46.9 Years STANDARD_DEVIATION 12.72 | 41.3 Years STANDARD_DEVIATION 14.68 | 43.4 Years STANDARD_DEVIATION 13.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 21 Participants | 23 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 22 Participants | 21 Participants | 22 Participants | 65 Participants |
| Region of Enrollment Australia | 4 participants | 2 participants | 2 participants | 8 participants |
| Region of Enrollment Europe | 18 participants | 18 participants | 20 participants | 56 participants |
| Region of Enrollment New Zealand | 1 participants | 1 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 12 Participants | 32 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 11 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 15 / 24 | 13 / 23 | 12 / 23 |
| serious Total, serious adverse events | 1 / 24 | 0 / 23 | 1 / 23 |
Outcome results
Primary
Change From Baseline (CFBL) in Chronic Sinusitis Symptom Scores at Week 4
Participants score their CS symptoms on a 4-point scale as follows: 0 = absent symptoms (no sign/symptom evident), 1 = mild symptoms (sign/symptom present but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable), 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping). The scores are summed and averaged over the proceeding 7 days; higher scores indicate higher severity of symptoms of CS.
Time frame: Week 4
Population: ITT analysis set: all randomized subjects who receive the study treatment or have a treatment attempt on Day 1 and have post-Day 1 assessments available
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 (Low Dose) | Change From Baseline (CFBL) in Chronic Sinusitis Symptom Scores at Week 4 | -2.24 score on a scale | Standard Error 0.637 |
| LYR-210 (High Dose) | Change From Baseline (CFBL) in Chronic Sinusitis Symptom Scores at Week 4 | -2.65 score on a scale | Standard Error 0.651 |
| Sham Procedure | Change From Baseline (CFBL) in Chronic Sinusitis Symptom Scores at Week 4 | -2.28 score on a scale | Standard Error 0.611 |
Secondary
CFBL in Chronic Sinusitis Symptom Scores at Week 24
Participants score their CS symptoms on a 4-point scale as follows: 0 = absent symptoms (no sign/symptom evident), 1 = mild symptoms (sign/symptom present but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable), 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping). The scores are summed and averaged over the proceeding 7 days; higher scores indicate higher severity of symptoms of CS.
Time frame: Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 (Low Dose) | CFBL in Chronic Sinusitis Symptom Scores at Week 24 | -3.36 score on a scale | Standard Error 0.668 |
| LYR-210 (High Dose) | CFBL in Chronic Sinusitis Symptom Scores at Week 24 | -4.32 score on a scale | Standard Error 0.682 |
| Sham Procedure | CFBL in Chronic Sinusitis Symptom Scores at Week 24 | -2.68 score on a scale | Standard Error 0.64 |
Secondary
Change From Baseline in the 22-item Sino-nasal Outcome Test (SNOT-22) Total Score at Week 24
Participants score the severity of their symptoms and social/emotional consequences of CS on a 6-point scale: 0 = no problem, 1 = very mild problem, 2 = mild or slight problem, 3 = moderate problem, 4 = severe problem, 5 = problem as bad as it can be. The scores are summed in the range of 0-110; higher scores indicate higher severity of symptoms or social/emotional consequences of CS.
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 (Low Dose) | Change From Baseline in the 22-item Sino-nasal Outcome Test (SNOT-22) Total Score at Week 24 | -30.0 score on a scale | Standard Error 5.32 |
| LYR-210 (High Dose) | Change From Baseline in the 22-item Sino-nasal Outcome Test (SNOT-22) Total Score at Week 24 | -40.7 score on a scale | Standard Error 5.76 |
| Sham Procedure | Change From Baseline in the 22-item Sino-nasal Outcome Test (SNOT-22) Total Score at Week 24 | -21.7 score on a scale | Standard Error 5.1 |
Secondary
Participants With Improved Bilateral Zinreich Score at Week 24
Each sinus is assigned a score based on the percentage of opacification as follows: 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76 % to 99%, 5 = 100% or completely occluded. Each sinus pair has a bilateral score in the range of 0 to 10. Higher scores indicate higher severity of sinus opacification. Responder is defined as a participant with at least a 1-point decrease in the imaging score at Week 24 compared with baseline.
Time frame: Week 24
Population: The outcome measure is based on the Intent-to-treat (ITT) set which includes all randomized subjects who received the study treatment and had a post-Day 1 imaging assessment which could be analyzed by the imaging core lab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LYR-210 (Low Dose) | Participants With Improved Bilateral Zinreich Score at Week 24 | 13 Participants |
| LYR-210 (High Dose) | Participants With Improved Bilateral Zinreich Score at Week 24 | 14 Participants |
| Sham Procedure | Participants With Improved Bilateral Zinreich Score at Week 24 | 10 Participants |
Secondary
Plasma Drug Concentrations of MF at Week 12
To evaluate the pharmacokinetics of LYR-210
Time frame: 12 weeks
Population: Participants who had evaluable plasma concentration at week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 (Low Dose) | Plasma Drug Concentrations of MF at Week 12 | 21.6500 pg/mL | Standard Deviation 7.77869 |
| LYR-210 (High Dose) | Plasma Drug Concentrations of MF at Week 12 | 30.9143 pg/mL | Standard Deviation 12.04657 |
Secondary
Plasma Drug Concentrations of MF at Week 4
To evaluate the pharmacokinetics of LYR-210
Time frame: 4 Weeks
Population: Participants who had evaluable plasma concentration at week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LYR-210 (Low Dose) | Plasma Drug Concentrations of MF at Week 4 | 13.6110 pg/mL | Standard Deviation 5.2171 |
| LYR-210 (High Dose) | Plasma Drug Concentrations of MF at Week 4 | 45.3500 pg/mL | Standard Deviation 11.40783 |
Secondary
The Number of Participants With Treatment-related Adverse Events for up to 24 Weeks
To evaluate the safety and tolerability of LYR-210
Time frame: 24 weeks
Population: The safety analysis population contains all subjects who were randomized and either received the study treatment (Sham or either dose of LYR-210) or had a treatment attempt on Day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LYR-210 (Low Dose) | The Number of Participants With Treatment-related Adverse Events for up to 24 Weeks | 11 Participants |
| LYR-210 (High Dose) | The Number of Participants With Treatment-related Adverse Events for up to 24 Weeks | 5 Participants |
| Sham Procedure | The Number of Participants With Treatment-related Adverse Events for up to 24 Weeks | 5 Participants |