Nasal Polyps
Conditions
Keywords
Depemokimab, GSK3511294, Chronic rhinosinusitis, Verbal response scale, Asthma Control Questionnaire, Lund Mackay computed tomography, Nasal polyps score, Nasal endoscopy
Brief summary
This study will evaluate the efficacy and safety of depemokimab (GSK3511294) in participants with Chronic rhinosinusitis with nasal polyps (CRSwNP).
Interventions
BIOLOGICALDepemokimab (GSK3511294)
Depemokimab (GSK3511294) was administered using a pre- filled syringe.
DRUGPlacebo
Placebo was administered as normal saline using a pre-filled syringe.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This will be a double-blind study.
Intervention model description
Participants will receive either depemokimab (GSK3511294) or placebo during the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with 18 years of age and older inclusive, at the time of signing the informed consent. * Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) assessed by the investigator. * Participants who have had at least one of the following at Visit 1: Previous nasal surgery for the removal of NP; have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of NP; medically unsuitable or intolerant to systemic corticosteroid. * Participants (except for those in Japan) must be on daily treatment with intranasal corticosteroids (INCS) (including intranasal liquid steroid wash/douching) for at least the 8 weeks immediately prior to screening. * Participants presenting with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity and loss of smell or rhinorrhea (runny nose) based on clinical assessment by the investigator. * Presence of symptoms of chronic rhinosinusitis as described by at least 2 different symptoms for at least 12 weeks prior to Visit 1, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), plus facial pain/pressure and/or reduction or loss of smell. * Male or eligible female participants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read) | Baseline (Day 1) and at Week 52 | Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The assessments were performed by central video image recordings of nasal endoscopy. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores were graded based on NP size, recorded as sum of the right and left nostril scores and ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores \[0 to 4\] in each nostril; with higher scores indicating worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. |
| Change From Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale From Week 49 Through to Week 52 | Baseline (Day 1) and from Week 49 to Week 52 | This endpoint evaluated the change from baseline in the mean nasal obstruction score using a Verbal Response Scale (VRS) from Week 49 through to Week 52. Participants used a VRS to rate nasal obstruction severity, with scores averaged over the specified period to assess treatment impact on nasal obstruction symptoms. Participants were asked to indicate the severity of nasal obstruction at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of electronic diary (eDiary) data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lund Mackay Computerized Tomography (CT) Score at Week 52 | Baseline (Day 1) and at Week 52 | The LMK CT scoring system is based on CT imaging of the sinuses with points given for degree of opacification: 0 =normal, 1 = partial opacification, 2 = total opacification. These points were applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side (right and left). The osteomeatal complex (OC) is graded as 0 = not occluded, or 2 = occluded. The range for the total LMK CT score is therefore 0 (normal) to 24 (total opacification) when summed across both sides with higher scores indicating more severe disease. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. |
| Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 | Baseline (Day 1) and at Week 52 | Sino-nasal outcome test-22 is a 22-item measure of disease specific health related quality of life (HRQoL). Participants were asked to rate the severity of their condition on each of the 22 items over the previous 2 weeks using a 6-point rating scale of 0-5 including: 0 = Not present/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 for each question were summed up to derive the total score range for the SNOT-22 was from 0 (high quality of life) to 110 (worst quality of life), where higher scores indicate worse quality of life. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. |
| Change From Baseline in Mean Nasal Obstruction Score (Verbal Response Scale) From Week 21 Through to Week 24 | Baseline (Day 1) and from Week 21 to Week 24 | Participants were asked to indicate the severity of nasal obstruction at its worst over the previous 24 hours using a 4-point VRS. The response options were no symptoms, mild symptoms, moderate symptoms, and severe symptoms, scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms). Higher scores indicate more severe status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 21-24. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. |
| Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 26 | Baseline (Day 1) and at Week 26 | Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The assessments were performed by central video image recordings of nasal endoscopy. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores were graded based on NP size, recorded as sum of the right and left nostril scores and ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores \[0 to 4\] in each nostril; with higher scores indicating worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. |
| Change From Baseline in Mean Symptom Score for Rhinorrhea (Runny Nose) Using Verbal Response Scale From Week 49 Through to Week 52 | Baseline (Day 1) and from Week 49 to Week 52 | Participants were asked to indicate the severity of rhinorrhea (runny nose) at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms). Higher scores indicate the worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. |
| Percentage of Participants Requiring First Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP up to Week 52 | Up to Week 52 | Nasal polyp surgery is defined as any procedure involving instruments resulting in incision and removal of tissue from the nasal cavity (for example polypectomy).Time to first nasal polyp surgery (actual) or disease-modulating medication for CRSwNP up to week 52 was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). The percentage of participants with nasal surgery or disease-modulating medication for CRSwNP and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method. |
| Percentage of Participants Requiring at Least One Course of Systemic Corticosteroids or Disease-Modulating Medication for CRSwNP or Nasal Surgery (Actual) During the Week 52 Treatment Period | Up to Week 52 | The percentage of participants requiring at least 1 course of systemic corticosteroids (CS) or disease-modulating medication for CRSwNP or nasal surgery (actual) during the Week 52 treatment period was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). Percentage of participants with nasal surgery or course of systemic CS for CRSwNP have been presented. |
| Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 52 | Baseline (Day 1) and at Week 52 | The ACQ-5 is a five-item questionnaire designed to be self-completed by the participants to assess the most common asthma symptoms. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheezing). The overall ACQ-5 response option is the mean score of all 5 questions representing 0 with no impairment/limitation and 6 as total impairment/ limitation. Higher scores indicated more limitations and lower scores with better asthma control. Impact on asthma control in the subgroup of participants with an ACQ-5 score greater than 0.75 (indicating partially or not well-controlled) at baseline was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. |
| Percentage of Participants Requiring First Nasal Surgery (Actual or Entry on Waiting List) or Disease-Modulating Medication for Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Up to Week 52 | Up to Week 52 | Nasal polyp surgery is defined as any procedure involving instruments resulting in incision and removal of tissue from the nasal cavity (for example polypectomy). Time to first nasal polyp surgery (actual or entry on waiting list) or disease-modulating medication for CRSwNP up to Week 52 was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). The percentage of participants with nasal surgery or disease-modulating medication for CRSwNP and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method. |
| Change From Baseline in Mean Symptom Score for Loss of Smell Using Verbal Response Scale From Week 49 Through to Week 52 | Baseline (Day 1) and from Week 49 to Week 52 | Participants were asked to indicate the severity of loss of smell at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms). Higher score indicates worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. |
Countries
Argentina, Belgium, Canada, China, France, Germany, Japan, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 276 participants were randomized to the study. Of which 271 participants were included in the Full analysis set (FAS) population. The FAS included all randomized participants who received at least 1 dose of study intervention excluding 4 participants from 1 site with Good clinical practice (GCP)/data integrity issues. One participant was randomized in error and did not receive any study drug.
Pre-assignment details
A total of 276 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Depemokimab Participants received a 100 mg dose of depemokimab SC injection once every 26 weeks (week 0 and week 26) over a treatment period of 52 weeks. Participants were to be maintained on their existing baseline maintenance for CRSwNP SOC treatment throughout the study. | 143 |
| Placebo Participants received placebo SC injection once every 26 weeks (week 0 and week 26) over a treatment period of 52 weeks. Participants were to be maintained on their existing baseline maintenance for CRSwNP SOC treatment throughout the study. | 128 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | GCP Violation | 0 | 4 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Randomized, not treated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 9 |
Baseline characteristics
| Characteristic | Placebo | Total | Depemokimab |
|---|---|---|---|
| Age, Continuous | 52.9 YEARS STANDARD_DEVIATION 13.49 | 53.5 YEARS STANDARD_DEVIATION 13.42 | 54.1 YEARS STANDARD_DEVIATION 13.37 |
| Race/Ethnicity, Customized ASIAN | 30 Participants | 67 Participants | 37 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 2 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized MISSING | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized UNKNOWN | 4 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized WHITE | 88 Participants | 185 Participants | 97 Participants |
| Sex: Female, Male Female | 38 Participants | 83 Participants | 45 Participants |
| Sex: Female, Male Male | 90 Participants | 188 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 143 | 0 / 128 |
| other Total, other adverse events | 71 / 143 | 72 / 128 |
| serious Total, serious adverse events | 5 / 143 | 6 / 128 |
Outcome results
Primary
Change From Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale From Week 49 Through to Week 52
This endpoint evaluated the change from baseline in the mean nasal obstruction score using a Verbal Response Scale (VRS) from Week 49 through to Week 52. Participants used a VRS to rate nasal obstruction severity, with scores averaged over the specified period to assess treatment impact on nasal obstruction symptoms. Participants were asked to indicate the severity of nasal obstruction at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of electronic diary (eDiary) data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and from Week 49 to Week 52
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale From Week 49 Through to Week 52 | -0.76 Scores on a Scale | Standard Error 0.079 |
| Placebo | Change From Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale From Week 49 Through to Week 52 | -0.53 Scores on a Scale | Standard Error 0.083 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNPp-value: 0.04795% CI: [-0.46, 0]Mixed Models Analysis
Primary
Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read)
Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The assessments were performed by central video image recordings of nasal endoscopy. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores were graded based on NP size, recorded as sum of the right and left nostril scores and ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores \[0 to 4\] in each nostril; with higher scores indicating worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and at Week 52
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read) | -0.6 Scores on a Scale | Standard Error 0.14 |
| Placebo | Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read) | 0.2 Scores on a Scale | Standard Error 0.15 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNPp-value: <0.00195% CI: [-1.1, -0.3]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 52
The ACQ-5 is a five-item questionnaire designed to be self-completed by the participants to assess the most common asthma symptoms. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheezing). The overall ACQ-5 response option is the mean score of all 5 questions representing 0 with no impairment/limitation and 6 as total impairment/ limitation. Higher scores indicated more limitations and lower scores with better asthma control. Impact on asthma control in the subgroup of participants with an ACQ-5 score greater than 0.75 (indicating partially or not well-controlled) at baseline was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and at Week 52
Population: For pooled studies of 217095 (NCT05274750) and 218079 (NCT05281523), the analysis was performed on the FAS population. The FAS included all randomized participants who took at least 1 dose of study drug excluding participants from 1 site for 217095 and 2 sites for 218079 respectively with GCP violation. Participants were analyzed according to the treatment they were allocated at randomization. The overall number of participants analyzed signifies participants evaluable for specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 52 | -0.75 Scores on a Scale | Standard Error 0.182 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 52 | 0.00 Scores on a Scale | Standard Error 0.182 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP (pooled analysis)p-value: 0.00495% CI: [-1.26, -0.25]Mixed Models Analysis
Secondary
Change From Baseline in Lund Mackay Computerized Tomography (CT) Score at Week 52
The LMK CT scoring system is based on CT imaging of the sinuses with points given for degree of opacification: 0 =normal, 1 = partial opacification, 2 = total opacification. These points were applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side (right and left). The osteomeatal complex (OC) is graded as 0 = not occluded, or 2 = occluded. The range for the total LMK CT score is therefore 0 (normal) to 24 (total opacification) when summed across both sides with higher scores indicating more severe disease. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and at Week 52
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Lund Mackay Computerized Tomography (CT) Score at Week 52 | -2.8 Scores on a Scale | Standard Error 0.45 |
| Placebo | Change From Baseline in Lund Mackay Computerized Tomography (CT) Score at Week 52 | -0.8 Scores on a Scale | Standard Error 0.46 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNPp-value: 0.00295% CI: [-3.3, -0.8]ANCOVA
Secondary
Change From Baseline in Mean Nasal Obstruction Score (Verbal Response Scale) From Week 21 Through to Week 24
Participants were asked to indicate the severity of nasal obstruction at its worst over the previous 24 hours using a 4-point VRS. The response options were no symptoms, mild symptoms, moderate symptoms, and severe symptoms, scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms). Higher scores indicate more severe status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 21-24. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and from Week 21 to Week 24
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Mean Nasal Obstruction Score (Verbal Response Scale) From Week 21 Through to Week 24 | -0.74 Scores on a Scale | Standard Error 0.071 |
| Placebo | Change From Baseline in Mean Nasal Obstruction Score (Verbal Response Scale) From Week 21 Through to Week 24 | -0.57 Scores on a Scale | Standard Error 0.074 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 21 to Week 24 in participants with a diagnosis of CRSwNPp-value: 0.09495% CI: [-0.37, 0.03]Mixed Models Analysis
Secondary
Change From Baseline in Mean Symptom Score for Loss of Smell Using Verbal Response Scale From Week 49 Through to Week 52
Participants were asked to indicate the severity of loss of smell at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms). Higher score indicates worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and from Week 49 to Week 52
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Mean Symptom Score for Loss of Smell Using Verbal Response Scale From Week 49 Through to Week 52 | -0.48 Scores on a Scale | Standard Error 0.069 |
| Placebo | Change From Baseline in Mean Symptom Score for Loss of Smell Using Verbal Response Scale From Week 49 Through to Week 52 | -0.29 Scores on a Scale | Standard Error 0.072 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 49 to Week 52 in participants with a diagnosis of CRSwNPp-value: 0.05595% CI: [-0.39, 0]Mixed Models Analysis
Secondary
Change From Baseline in Mean Symptom Score for Rhinorrhea (Runny Nose) Using Verbal Response Scale From Week 49 Through to Week 52
Participants were asked to indicate the severity of rhinorrhea (runny nose) at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms). Higher scores indicate the worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and from Week 49 to Week 52
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Mean Symptom Score for Rhinorrhea (Runny Nose) Using Verbal Response Scale From Week 49 Through to Week 52 | -0.71 Scores on a Scale | Standard Error 0.084 |
| Placebo | Change From Baseline in Mean Symptom Score for Rhinorrhea (Runny Nose) Using Verbal Response Scale From Week 49 Through to Week 52 | -0.49 Scores on a Scale | Standard Error 0.087 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 49 to Week 52 in participants with a diagnosis of CRSwNPp-value: 0.07495% CI: [-0.46, 0.02]Mixed Models Analysis
Secondary
Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52
Sino-nasal outcome test-22 is a 22-item measure of disease specific health related quality of life (HRQoL). Participants were asked to rate the severity of their condition on each of the 22 items over the previous 2 weeks using a 6-point rating scale of 0-5 including: 0 = Not present/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 for each question were summed up to derive the total score range for the SNOT-22 was from 0 (high quality of life) to 110 (worst quality of life), where higher scores indicate worse quality of life. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and at Week 52
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 | -13.3 Scores on a Scale | Standard Error 2.96 |
| Placebo | Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 | -6.5 Scores on a Scale | Standard Error 3.08 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNPp-value: 0.11395% CI: [-15.2, 1.6]Mixed Models Analysis
Secondary
Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 26
Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The assessments were performed by central video image recordings of nasal endoscopy. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores were graded based on NP size, recorded as sum of the right and left nostril scores and ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores \[0 to 4\] in each nostril; with higher scores indicating worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time frame: Baseline (Day 1) and at Week 26
Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. The overall number of participants analyzed represents only those participants available at the specified time points and evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Depemokimab | Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 26 | -0.6 Scores on a Scale | Standard Error 0.13 |
| Placebo | Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 26 | 0.1 Scores on a Scale | Standard Error 0.13 |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 26 in participants with a diagnosis of CRSwNPp-value: <0.00195% CI: [-1.1, -0.4]Mixed Models Analysis
Secondary
Percentage of Participants Requiring at Least One Course of Systemic Corticosteroids or Disease-Modulating Medication for CRSwNP or Nasal Surgery (Actual) During the Week 52 Treatment Period
The percentage of participants requiring at least 1 course of systemic corticosteroids (CS) or disease-modulating medication for CRSwNP or nasal surgery (actual) during the Week 52 treatment period was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). Percentage of participants with nasal surgery or course of systemic CS for CRSwNP have been presented.
Time frame: Up to Week 52
Population: For pooled studies of 217095 (NCT05274750) and 218079 (NCT05281523), the analysis was performed on the FAS population. The FAS included all randomized participants who took at least 1 dose of study treatment excluding participants from 1 site for 217095 and 2 sites for 218079 respectively with GCP violation. Participants were analyzed according to the treatment they were allocated at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Depemokimab | Percentage of Participants Requiring at Least One Course of Systemic Corticosteroids or Disease-Modulating Medication for CRSwNP or Nasal Surgery (Actual) During the Week 52 Treatment Period | 26 Percentage of participants |
| Placebo | Percentage of Participants Requiring at Least One Course of Systemic Corticosteroids or Disease-Modulating Medication for CRSwNP or Nasal Surgery (Actual) During the Week 52 Treatment Period | 36 Percentage of participants |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP (pooled analysis)p-value: 0.00695% CI: [0.4, 0.86]Regression, Logistic
Secondary
Percentage of Participants Requiring First Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP up to Week 52
Nasal polyp surgery is defined as any procedure involving instruments resulting in incision and removal of tissue from the nasal cavity (for example polypectomy).Time to first nasal polyp surgery (actual) or disease-modulating medication for CRSwNP up to week 52 was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). The percentage of participants with nasal surgery or disease-modulating medication for CRSwNP and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method.
Time frame: Up to Week 52
Population: For pooled studies of 217095 (NCT05274750) and 218079 (NCT05281523), the analysis was performed on the FAS population. The FAS included all randomized participants who took at least 1 dose of study treatment excluding participants from 1 site for 217095 and 2 sites for 218079 respectively with GCP violation. Participants were analyzed according to the treatment they were allocated at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Depemokimab | Percentage of Participants Requiring First Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP up to Week 52 | 12.2 Percentage of participants |
| Placebo | Percentage of Participants Requiring First Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP up to Week 52 | 16.7 Percentage of participants |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP (pooled analysis)p-value: 0.14695% CI: [0.453, 1.124]Cox Proportional Hazards Model
Secondary
Percentage of Participants Requiring First Nasal Surgery (Actual or Entry on Waiting List) or Disease-Modulating Medication for Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Up to Week 52
Nasal polyp surgery is defined as any procedure involving instruments resulting in incision and removal of tissue from the nasal cavity (for example polypectomy). Time to first nasal polyp surgery (actual or entry on waiting list) or disease-modulating medication for CRSwNP up to Week 52 was assessed in a pre-specified pooled analysis across replicate studies 217095 (NCT05274750) and 218079 (NCT05281523). The percentage of participants with nasal surgery or disease-modulating medication for CRSwNP and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method.
Time frame: Up to Week 52
Population: For pooled studies of 217095 (NCT05274750) and 218079 (NCT05281523), the analysis was performed on the FAS population. The FAS included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site for 217095 and 2 sites for 218079 respectively with GCP violation. Participants were analyzed according to the treatment they were allocated at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Depemokimab | Percentage of Participants Requiring First Nasal Surgery (Actual or Entry on Waiting List) or Disease-Modulating Medication for Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Up to Week 52 | 15.0 Percentage of participants |
| Placebo | Percentage of Participants Requiring First Nasal Surgery (Actual or Entry on Waiting List) or Disease-Modulating Medication for Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Up to Week 52 | 21.9 Percentage of participants |
Comparison: To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP (pooled analysis)p-value: 0.12895% CI: [0.495, 1.092]Cox Proportional Hazards Model