Chronic Rhinosinusitis (Diagnosis), Chronic Sinusitis
Conditions
Brief summary
This study will assess the safety, tolerability, pharmacokinetics and efficacy of two LYR-220 designs in symptomatic adult chronic rhinosinusitis (CRS) subjects who have had a prior functional endoscopic sinus surgery.
Detailed description
This is a Phase II, Patient-blinded, Two-part, Randomized, Parallel-group Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of LYR-220. The study will consist of two parts: Part 1 will enroll up to 10 patients and is open label. Part 2 is randomized, sham controlled and will enroll approximately 40 patients. The study follow-up duration is 28 weeks.
Interventions
DRUGLYR-220 Design 1 (Part 1 only)
LYR-220 drug matrix (mometasone furoate 7500 µg) Design 1
DRUGLYR-220 Design 2 (Part 1 and Part 2)
LYR-220 drug matrix (mometasone furoate 7500 µg) Design 2
DRUGBilateral sham procedure control (Part 2)
Bilateral sham procedure control
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 chronic rhinosinusitis. * Has had a prior bilateral total ethmoidectomy. * Has computed tomography (CT) ethmoid cavity opacification. * Has a Sinonasal Outcome Test (SNOT-22) ≥ 20 at Screening Visit. * Minimum cardinal symptom score. * 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 or regulatory authority if applicable by national law. * Agrees to comply with all study requirements.
Exclusion criteria
* 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. * Had dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. * Past or present functional vision in only one eye. * Past, present, or planned organ transplant or chemotherapy with immunosuppression. * With prior cataract surgery or presence (in either eye) of posterior subcapsular cataract of grade 2 or higher, nuclear cataract of grade 3 or higher, or cortical cataract of grade 2 or higher or involving a minimum of center optic zone of 3 mm diameter. * Ethmoidectomy that was unilateral or partial. * Currently participating in an investigational drug or device study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Product-related Unexpected Serious Adverse Events | Through Week 28 | Product-related unexpected serious adverse events |
| Plasma MF Concentrations | Through Week 25 | Plasma MF concentrations at 1 hour post study treatment administration and at Days 2 or 3, days 5 or 8, and Weeks 4,12,16 or 20, 24 and 25. The PK analysis will be performed based on subjects with available plasma MF concentration data post Day 1 administration procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ophthalmic Assessment: Intraocular Pressure (IOP) | Through Week 25 | Percentage of subjects with clinically significant increase in IOP |
| Ophthalmic Assessment: Cataract | Through Week 25 | Percentage of subjects with newly identified or worsened cataract in one or both eyes |
| Adverse Events | Through Week 28 | Percentage of subjects reporting treatment-emergent adverse events |
| Change From Baseline in the Average Composite Score Over the Preceeding 7 Days of the 3 Cardinal Symptoms (3CS) | Through Week 28 | Change from baseline in the average composite score over the preceeding 7 days of the 3 Cardinal Symptoms (3CS).The 3CS include: nasal blockage/obstruction/congestion, facial pain/ pressure, and anterior/posterior nasal discharge. The diary is completed daily by study participants throughout the study. Each symptom/each question is scored daily on a 0-3 scale as follows: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms. |
| Improving Chronic Rhinosinusitis (CRS) Specific Quality of Life as Per the 22-item Sino-nasal Outcome Test (SNOT-22) Questionnaire | Through Week 28 | The 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire is a 22-item disease-specific quality of life instrument validated for use in CRS. Each symptom is scored as it has been over the past 2 weeks on a 6-point scale as follows: 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 outcome measure is change from baseline in total patient-reported outcome score. The SNOT-22 total score is the sum of individual scores and ranges from 0 to 110. Higher scores indicate higher severity of symptoms. |
| Endoscopic Findings | Through Week 25 | Percentage of subjects with newly identified or worsened endoscopic findings in the ethmoid cavity (mild, moderate, or severe) |
Countries
Australia, United States
Participant flow
Recruitment details
2 subjects were randomized but did not receive the investigational product and are not included in the total count
Participants by arm
| Arm | Count |
|---|---|
| Part 1: LYR-220 Design 1 Bilateral insertion of LYR-220 drug matrix (mometasone furoate 7500 µg) Design 1 LYR-220 Design 1: LYR-220 drug matrix (mometasone furoate 7500 µg) Design 1 | 3 |
| Part 1 and Part 2: LYR-220 Design 2 Bilateral insertion of LYR-220 drug matrix (mometasone furoate 7500 µg) Design 2 LYR-220 Design 2: LYR-220 drug matrix (mometasone furoate 7500 µg) Design 2 | 24 |
| Part 2: Bilateral Sham Procedure Bilateral sham procedure control Bilateral sham procedure control: Bilateral sham procedure control | 21 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Bilateral Dislodgement | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Part 1: LYR-220 Design 1 | Part 1 and Part 2: LYR-220 Design 2 | Part 2: Bilateral Sham Procedure | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 23 Participants | 18 Participants | 43 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 14.98 | 48 years STANDARD_DEVIATION 12.91 | 55 years STANDARD_DEVIATION 11.29 | 51 years STANDARD_DEVIATION 12.49 |
| BMI | 35.35 kg/m² STANDARD_DEVIATION 6.69 | 30.65 kg/m² STANDARD_DEVIATION 5.68 | 33.71 kg/m² STANDARD_DEVIATION 8.63 | 32.26 kg/m² STANDARD_DEVIATION 7.23 |
| 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 | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 22 Participants | 18 Participants | 43 Participants |
| Region of Enrollment Australia | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United States | 3 Participants | 20 Participants | 21 Participants | 44 Participants |
| Sex: Female, Male Female | 1 Participants | 16 Participants | 11 Participants | 28 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 24 | 0 / 21 |
| other Total, other adverse events | 1 / 3 | 21 / 24 | 9 / 21 |
| serious Total, serious adverse events | 0 / 3 | 0 / 24 | 0 / 21 |
Outcome results
Primary
Plasma MF Concentrations
Plasma MF concentrations at 1 hour post study treatment administration and at Days 2 or 3, days 5 or 8, and Weeks 4,12,16 or 20, 24 and 25. The PK analysis will be performed based on subjects with available plasma MF concentration data post Day 1 administration procedure.
Time frame: Through Week 25
Population: PK Analysis Set Design 1- Part 1, PK Analysis Set Design 2 - Part 1; PK Analysis Set Design 2 - Part 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | 1-Hour Post | 11.04 pg/mL | Standard Deviation 0.04 |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Day 8 | 68.34 pg/mL | Standard Deviation 38.67 |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Week 24 | 2.08 pg/mL | Standard Deviation 2.14 |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Week 4 | 40.41 pg/mL | Standard Deviation 25.99 |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Week 20 | 7.58 pg/mL | Standard Deviation 5.31 |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Day 3 | 97.77 pg/mL | — |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Day 2 | 40.86 pg/mL | Standard Deviation 5.98 |
| Part 1: LYR-220 Design 1 | Plasma MF Concentrations | Week 12 | 15.14 pg/mL | Standard Deviation 4.26 |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Week 4 | 68.90 pg/mL | Standard Deviation 5.19 |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Day 2 | 135.83 pg/mL | — |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Day 3 | 55.86 pg/mL | Standard Deviation 28.7 |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Day 8 | 72.31 pg/mL | Standard Deviation 19.15 |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Week 12 | 68.00 pg/mL | Standard Deviation 20.96 |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Week 16 | 70.940 pg/mL | — |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Week 20 | 22.6 pg/mL | Standard Deviation 1 |
| Part 1 and Part 2: LYR-220 Design 2 | Plasma MF Concentrations | Week 24 | 11.52 pg/mL | Standard Deviation 8.77 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | 1-Hour Post | 18.11 pg/mL | Standard Deviation 13.09 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Week 12 | 50.17 pg/mL | Standard Deviation 17.79 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Week 25 | NA pg/mL | — |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Week 16 | 31.26 pg/mL | Standard Deviation 17.06 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Day 2 | 61.02 pg/mL | Standard Deviation 23.98 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Week 24 | 11.18 pg/mL | Standard Deviation 12.96 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Week 20 | 20.17 pg/mL | Standard Deviation 8.49 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Day 8 | 58.87 pg/mL | Standard Deviation 21.36 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Day 5 | 44.16 pg/mL | Standard Deviation 19.6 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Week 4 | 61.31 pg/mL | Standard Deviation 34.97 |
| Part 2: Bilateral Sham Procedure | Plasma MF Concentrations | Day 3 | 46.00 pg/mL | Standard Deviation 26.05 |
Primary
Product-related Unexpected Serious Adverse Events
Product-related unexpected serious adverse events
Time frame: Through Week 28
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: LYR-220 Design 1 | Product-related Unexpected Serious Adverse Events | 0 Participants |
| Part 1 and Part 2: LYR-220 Design 2 | Product-related Unexpected Serious Adverse Events | 0 Participants |
| Part 2: Bilateral Sham Procedure | Product-related Unexpected Serious Adverse Events | 0 Participants |
Secondary
Adverse Events
Percentage of subjects reporting treatment-emergent adverse events
Time frame: Through Week 28
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: LYR-220 Design 1 | Adverse Events | 1 Participants |
| Part 1 and Part 2: LYR-220 Design 2 | Adverse Events | 23 Participants |
| Part 2: Bilateral Sham Procedure | Adverse Events | 16 Participants |
Secondary
Change From Baseline in the Average Composite Score Over the Preceeding 7 Days of the 3 Cardinal Symptoms (3CS)
Change from baseline in the average composite score over the preceeding 7 days of the 3 Cardinal Symptoms (3CS).The 3CS include: nasal blockage/obstruction/congestion, facial pain/ pressure, and anterior/posterior nasal discharge. The diary is completed daily by study participants throughout the study. Each symptom/each question is scored daily on a 0-3 scale as follows: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms.
Time frame: Through Week 28
Population: Efficacy Analysis Set - Part 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: LYR-220 Design 1 | Change From Baseline in the Average Composite Score Over the Preceeding 7 Days of the 3 Cardinal Symptoms (3CS) | -1.68 Change from Baseline in 3CS Score | Standard Deviation 2.33 |
| Part 1 and Part 2: LYR-220 Design 2 | Change From Baseline in the Average Composite Score Over the Preceeding 7 Days of the 3 Cardinal Symptoms (3CS) | -0.48 Change from Baseline in 3CS Score | Standard Deviation 2.1 |
Secondary
Endoscopic Findings
Percentage of subjects with newly identified or worsened endoscopic findings in the ethmoid cavity (mild, moderate, or severe)
Time frame: Through Week 25
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: LYR-220 Design 1 | Endoscopic Findings | 0 Participants |
| Part 1 and Part 2: LYR-220 Design 2 | Endoscopic Findings | 6 Participants |
| Part 2: Bilateral Sham Procedure | Endoscopic Findings | 3 Participants |
Secondary
Improving Chronic Rhinosinusitis (CRS) Specific Quality of Life as Per the 22-item Sino-nasal Outcome Test (SNOT-22) Questionnaire
The 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire is a 22-item disease-specific quality of life instrument validated for use in CRS. Each symptom is scored as it has been over the past 2 weeks on a 6-point scale as follows: 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 outcome measure is change from baseline in total patient-reported outcome score. The SNOT-22 total score is the sum of individual scores and ranges from 0 to 110. Higher scores indicate higher severity of symptoms.
Time frame: Through Week 28
Population: Efficacy Analysis Set - Part 2
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: LYR-220 Design 1 | Improving Chronic Rhinosinusitis (CRS) Specific Quality of Life as Per the 22-item Sino-nasal Outcome Test (SNOT-22) Questionnaire | -30.1 Change from Baseline in SNOT-22 score |
| Part 1 and Part 2: LYR-220 Design 2 | Improving Chronic Rhinosinusitis (CRS) Specific Quality of Life as Per the 22-item Sino-nasal Outcome Test (SNOT-22) Questionnaire | -4.0 Change from Baseline in SNOT-22 score |
Secondary
Ophthalmic Assessment: Cataract
Percentage of subjects with newly identified or worsened cataract in one or both eyes
Time frame: Through Week 25
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: LYR-220 Design 1 | Ophthalmic Assessment: Cataract | Newly Identified Cataract | 0 Participants |
| Part 1: LYR-220 Design 1 | Ophthalmic Assessment: Cataract | Worsened Cataract | 0 Participants |
| Part 1 and Part 2: LYR-220 Design 2 | Ophthalmic Assessment: Cataract | Newly Identified Cataract | 1 Participants |
| Part 1 and Part 2: LYR-220 Design 2 | Ophthalmic Assessment: Cataract | Worsened Cataract | 1 Participants |
| Part 2: Bilateral Sham Procedure | Ophthalmic Assessment: Cataract | Newly Identified Cataract | 0 Participants |
| Part 2: Bilateral Sham Procedure | Ophthalmic Assessment: Cataract | Worsened Cataract | 0 Participants |
Secondary
Ophthalmic Assessment: Intraocular Pressure (IOP)
Percentage of subjects with clinically significant increase in IOP
Time frame: Through Week 25
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: LYR-220 Design 1 | Ophthalmic Assessment: Intraocular Pressure (IOP) | IOP in 1 or both eyes >23 mm Hg at Post Baseline | 0 participants |
| Part 1: LYR-220 Design 1 | Ophthalmic Assessment: Intraocular Pressure (IOP) | An increase of IOP from Baseline in 1 or both eyes >=10 mm Hg | 0 participants |
| Part 1 and Part 2: LYR-220 Design 2 | Ophthalmic Assessment: Intraocular Pressure (IOP) | IOP in 1 or both eyes >23 mm Hg at Post Baseline | 0 participants |
| Part 1 and Part 2: LYR-220 Design 2 | Ophthalmic Assessment: Intraocular Pressure (IOP) | An increase of IOP from Baseline in 1 or both eyes >=10 mm Hg | 0 participants |
| Part 2: Bilateral Sham Procedure | Ophthalmic Assessment: Intraocular Pressure (IOP) | IOP in 1 or both eyes >23 mm Hg at Post Baseline | 0 participants |
| Part 2: Bilateral Sham Procedure | Ophthalmic Assessment: Intraocular Pressure (IOP) | An increase of IOP from Baseline in 1 or both eyes >=10 mm Hg | 0 participants |