Clinical Trial Results:
A Randomised, Double-blind, Parallel Group Phase III Study to Assess the Efficacy and Safety of 100 mg SC Depemokimab in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) - ANCHOR-2 (depemokimAb iN CHrOnic Rhinosinusitis)
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Summary
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EudraCT number |
2021-005055-36 |
Trial protocol |
IT SE ES PL |
Global end of trial date |
06 Aug 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Jul 2025
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First version publication date |
25 Jul 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
218079
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05281523 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford,Middlesex, United Kingdom, TW8 9GS
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Sep 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Jul 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Aug 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of depemokimab 100 milligram (mg) subcutaneous + standard of care (SOC) compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP
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Protection of trial subjects |
NA
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Apr 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 23
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Country: Number of subjects enrolled |
Poland: 60
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Country: Number of subjects enrolled |
Romania: 31
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Country: Number of subjects enrolled |
Spain: 42
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Country: Number of subjects enrolled |
Sweden: 10
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Country: Number of subjects enrolled |
United States: 20
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Country: Number of subjects enrolled |
China: 32
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Country: Number of subjects enrolled |
Japan: 28
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Country: Number of subjects enrolled |
Türkiye: 18
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Worldwide total number of subjects |
264
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EEA total number of subjects |
166
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
219
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From 65 to 84 years |
45
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 264 participants were randomized of which 257 participants were included in Full Analysis Set (FAS) population. The FAS included all randomized participants who received at least 1 dose of study intervention excluding 7 participants from 2 sites with good clinical practice (GCP)/data integrity issues. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 264 participants were enrolled in the study. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Assessor | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Depemokimab | |||||||||||||||||||||
Arm description |
Participants received a 100 milligram (mg) dose of depemokimab subcutaneous (SC) injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) standard of care (SOC) treatment throughout the study. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
GSK3511294
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
100 milligram (mg) once every 26 weeks
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Participants received placebo SC injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Matching Placebo once every 26 weeks
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Of 264 participants who were randomized, 7 participants from 2 sites were excluded from the full analysis population due to data integrity concerns & GCP violations, A total of 257 participants received treatment and were included in the Full analysis set population |
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Baseline characteristics reporting groups
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Reporting group title |
Depemokimab
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Reporting group description |
Participants received a 100 milligram (mg) dose of depemokimab subcutaneous (SC) injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) standard of care (SOC) treatment throughout the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo SC injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Pooled Depemokimab
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This reporting arm contains the pooled population of treated participants from the clinical trial groups "Depemokimab" study intervention from protocol 217095 (2021-005037-16) and protocol 218079 (2021-005055-36). Participants received a 100 mg dose of depemokimab SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study. Due to EudraCT template restriction, the number of subjects entered cannot exceed the number of subjects enrolled in 218079, ANCHOR-2 study (264). However, a total of 272 participants were included in the pooled analysis comprising of 143 participants from 217095 study and 129 participants from 218079 study who received depemokimab as study intervention.
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Subject analysis set title |
Pooled Placebo
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This reporting arm contains the pooled population of participants from the clinical trial groups "Placebo" study intervention from protocol 217095 and protocol 218079. Participants received a placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study.
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End points reporting groups
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Reporting group title |
Depemokimab
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Reporting group description |
Participants received a 100 milligram (mg) dose of depemokimab subcutaneous (SC) injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) standard of care (SOC) treatment throughout the study. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo SC injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study. | ||
Subject analysis set title |
Pooled Depemokimab
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This reporting arm contains the pooled population of treated participants from the clinical trial groups "Depemokimab" study intervention from protocol 217095 (2021-005037-16) and protocol 218079 (2021-005055-36). Participants received a 100 mg dose of depemokimab SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study. Due to EudraCT template restriction, the number of subjects entered cannot exceed the number of subjects enrolled in 218079, ANCHOR-2 study (264). However, a total of 272 participants were included in the pooled analysis comprising of 143 participants from 217095 study and 129 participants from 218079 study who received depemokimab as study intervention.
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Subject analysis set title |
Pooled Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This reporting arm contains the pooled population of participants from the clinical trial groups "Placebo" study intervention from protocol 217095 and protocol 218079. Participants received a placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study.
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End point title |
Change From Baseline in Total Endoscopic Nasal Polyps (NP) Score at Week 52 (Centrally Read) | ||||||||||||
End point description |
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. The right & left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate; 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 & ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores in each nostril; with higher scores indicating worse status. Baseline=Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. FAS population excluding participants from 2 sites with GCP violation. Only those participants with data available at specified time points have been analyzed.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) and at Week 52
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP
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Comparison groups |
Placebo v Depemokimab
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Number of subjects included in analysis |
255
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Analysis specification |
Pre-specified
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Analysis type |
[1] | ||||||||||||
P-value |
= 0.004 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-0.6
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1 | ||||||||||||
upper limit |
-0.2 | ||||||||||||
| Notes [1] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps, visit, visit by baseline, and visit by treatment group. |
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End point title |
Change From Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale from Week 49 Through to Week 52 | ||||||||||||
End point description |
This endpoint evaluated the change from baseline in the mean nasal obstruction score using a VRS from Week 49 through 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). Baseline was defined as the average score from the 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. The FAS included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites due to GCP violation. Only those participants with data available at specified time points have been analyzed.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) and from Week 49 to Week 52
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Statistical analysis title |
Statistical Analysis 3 | ||||||||||||
Statistical analysis description |
To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP
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Comparison groups |
Placebo v Depemokimab
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
[2] | ||||||||||||
P-value |
= 0.025 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-0.25
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.46 | ||||||||||||
upper limit |
-0.03 | ||||||||||||
| Notes [2] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps visit, visit by baseline and visit by treatment group. |
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End point title |
Change from Baseline in Mean Symptom Score for Rhinorrhea (Runny Nose) Using Verbal Response Scale from Week 49 Through to Week 52 | ||||||||||||
End point description |
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 indicated the worst status. Baseline was defined as the average score from the 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. The FAS included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites due to GCP violation. Participants were analyzed according to the treatment they were allocated at randomization. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and from Week 49 to Week 52
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Statistical analysis title |
Statistical Analysis 4 | ||||||||||||
Statistical analysis description |
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 CRSwNP
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Comparison groups |
Placebo v Depemokimab
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
[3] | ||||||||||||
P-value |
= 0.125 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-0.18
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.4 | ||||||||||||
upper limit |
0.05 | ||||||||||||
| Notes [3] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps visit, visit by baseline and visit by treatment group. |
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End point title |
Change From Baseline in Mean Symptom Score for Loss of Smell From Week 49 Through to Week 52 | ||||||||||||
End point description |
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 scores indicated worse status. Baseline was defined as the average score from the 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. The FAS included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites with GCP violation. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and from Week 49 to Week 52
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Statistical analysis title |
Statistical Analysis 4 | ||||||||||||
Statistical analysis description |
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 CRSwNP
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Comparison groups |
Placebo v Depemokimab
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
[4] | ||||||||||||
P-value |
= 0.007 [5] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-0.26
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.45 | ||||||||||||
upper limit |
-0.07 | ||||||||||||
| Notes [4] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps, visit, subgroup, visit by baseline, visit by treatment group. [5] - Nominal significance (i.e., p<0.05 without multiplicity control). However, statistical significance was not achieved due to a break in the multiplicity-controlled testing hierarchy. |
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End point title |
Change from Baseline in Lund Mackay (LMK) Computed Tomography (CT) Score at Week 52 | ||||||||||||
End point description |
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 are then 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 deriving a maximum score of 12 per side. The range for the total LMK CT score is therefore 0 (normal) to 24 (total opacification) when summed across both sides. Higher scores indicated more severe disease. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. The FAS included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites with GCP violation. Only those participants with data available at specified time points have been analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and at Week 52
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Statistical analysis title |
Statistical Analysis 5 | ||||||||||||
Statistical analysis description |
To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP
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Comparison groups |
Placebo v Depemokimab
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Number of subjects included in analysis |
232
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Analysis specification |
Pre-specified
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Analysis type |
[6] | ||||||||||||
P-value |
< 0.001 [7] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-3.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-4.4 | ||||||||||||
upper limit |
-2 | ||||||||||||
| Notes [6] - Analysis performed using an analysis of covariance model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region and previous surgery for nasal polyps. [7] - Nominal significance (i.e., p<0.05 without multiplicity control). However, statistical significance was not achieved due to a break in the multiplicity-controlled testing hierarchy. |
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End point title |
Change from Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52 | ||||||||||||
End point description |
SNOT-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 (not present/no problem) to 5 (Problem as bad as it can be). The total score range for the SNOT-22 is 0-110, where higher scores indicate greater disease impact. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. The full analysis set included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites with GCP violation. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.
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End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) and at Week 52
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 6 | ||||||||||||
Statistical analysis description |
To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP
|
||||||||||||
Comparison groups |
Placebo v Depemokimab
|
||||||||||||
Number of subjects included in analysis |
252
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
[8] | ||||||||||||
P-value |
= 0.015 [9] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-9.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-17.9 | ||||||||||||
upper limit |
-2 | ||||||||||||
| Notes [8] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps, visit, visit by baseline, and visit by treatment group. [9] - Nominal significance (i.e., p<0.05 without multiplicity control). However, statistical significance was not achieved due to a break in the multiplicity-controlled testing hierarchy. |
|||||||||||||
|
|||||||||||||
End point title |
Change from Baseline in Total Endoscopic Nasal Polyps Score at Week 26 | ||||||||||||
End point description |
Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The right & left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate; 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 & left nostril scores & ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores 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. The FAS included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites due to GCP violation. Only those participants with data available at specified time points have been analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) and at Week 26
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 8 | ||||||||||||
Statistical analysis description |
To assess the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 26 in participants with a diagnosis of CRSwNP
|
||||||||||||
Comparison groups |
Placebo v Depemokimab
|
||||||||||||
Number of subjects included in analysis |
255
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
[10] | ||||||||||||
P-value |
= 0.066 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-0.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.7 | ||||||||||||
upper limit |
0 | ||||||||||||
| Notes [10] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps, visit, visit by baseline, and visit by treatment group. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline in Mean Nasal Obstruction Score (VRS) From Week 21 Through to Week 24 | ||||||||||||
End point description |
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 indicated more severe status. Baseline was defined as the average score from the 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value. The full analysis set included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 sites with GCP violation. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) and from Week 21 to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 6 | ||||||||||||
Statistical analysis description |
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 CRSwNP
|
||||||||||||
Comparison groups |
Placebo v Depemokimab
|
||||||||||||
Number of subjects included in analysis |
256
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
[11] | ||||||||||||
P-value |
= 0.016 [12] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
LS Mean | ||||||||||||
Point estimate |
-0.24
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.43 | ||||||||||||
upper limit |
-0.04 | ||||||||||||
| Notes [11] - Analysis performed using a repeated measures model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps, visit, visit by baseline, and visit by treatment group. [12] - Nominal significance (i.e., p<0.05 without multiplicity control). However, statistical significance was not achieved due to a break in the multiplicity-controlled testing hierarchy. |
|||||||||||||
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
Nasal polyp surgery is defined as any procedure involving instruments resulting in incision & removal of tissue from the nasal cavity. Time to first nasal 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 (2021-005037-16) & 218079 (2021-005055-36). The percentage of participants with corresponding 95%CI have been presented, calculated using the Kaplan-Meier method. Analysis was performed on FAS which consisted of all randomized participants from study 217095 and 218079 (Pooled analysis) & who had at least 1 dose of study drug excluding participants from 3 sites with GCP violation. Due to EudraCT template restriction, the number of subjects (N) entered cannot exceed subjects 264 enrolled in 218079 study. But the depemokimab pooled arm included 272 participants comprising 143 participants from 217095 & 129 participants from 218079 & for all pooled analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Week 52
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 9 | ||||||||||||
Statistical analysis description |
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)
|
||||||||||||
Comparison groups |
Pooled Placebo v Pooled Depemokimab
|
||||||||||||
Number of subjects included in analysis |
528
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
[13] | ||||||||||||
P-value |
= 0.128 | ||||||||||||
Method |
Cox Proportional Hazards Model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.735
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.495 | ||||||||||||
upper limit |
1.092 | ||||||||||||
| Notes [13] - Cox Proportional Hazards Model with covariates of treatment, baseline total endoscopic nasal polyps score, baseline nasal obstruction score (VRS), log(e) baseline blood eosinophil count, region, study and previous surgery for nasal polyps. |
|||||||||||||
|
||||||||||
End point title |
Percentage of Participants Requiring at Least One Course of Systemic Corticosteroids or Disease-Modifying Medication for CRSwNP or Nasal Surgery (Actual) During the Week 52 Treatment Period | |||||||||
End point description |
Percentage of participants requiring at least 1 course of systemic corticosteroids 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 (2021-005037-16) and 218079 (2021-005055-36). Analysis was performed on the FAS which consisted of all randomized participants from study 217095 and 218079 (Pooled analysis) and who had at least 1 dose of study treatment excluding participants from 3 sites with GCP violation. Due to template limitations, the number of subjects (N) entered cannot exceed subjects 264 enrolled in 218079 study. But depemokimab pooled arm included 272 participants comprising 143 participants (217095 study) and 129 participants (218079 study) and for all pooled analysis.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Week 52
|
|||||||||
|
||||||||||
Statistical analysis title |
Statistical Analysis 11 | |||||||||
Statistical analysis description |
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)
|
|||||||||
Comparison groups |
Pooled Depemokimab v Pooled Placebo
|
|||||||||
Number of subjects included in analysis |
528
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
[14] | |||||||||
P-value |
= 0.006 [15] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.58
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.4 | |||||||||
upper limit |
0.86 | |||||||||
| Notes [14] - Logistic regression with covariates of treatment, number of courses of systemic corticosteroids in 12 months prior to screening for NP (0, 1, >1), log(e) baseline blood eosinophil count, baseline total endoscopic nasal polyps score, baseline nasal obstruction score (VRS), region, study and previous surgery for nasal polyps. [15] - Nominal significance (i.e., p<0.05 without multiplicity control) was achieved. However, statistical significance was not achieved due to a break in the multiplicity-controlled testing hierarchy. |
||||||||||
|
|||||||||||||
End point title |
Percentage of Participants Requiring First Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP up to Week 52 | ||||||||||||
End point description |
Nasal polyp surgery is defined as any procedure involving instruments resulting in incision & removal of tissue from the nasal cavity (e.g. polypectomy).Time to first nasal surgery (actual) or disease-modulating medication for CRSwNP up to Week 52 was assessed in a pre-specified pooled analysis across replicate studies 217095 (2021-005037-16) and 218079 (2021-005055-36). The percentage of participants with corresponding 95%CI have been presented, calculated using the Kaplan-Meier method. Analysis was performed on the FAS which consisted of all randomized participants from study 217095 and 218079 (Pooled analysis) and who had at least 1 dose of study treatment excluding participants from 3 sites with GCP violation. Due to EudraCT template restriction, the number of subjects (N) entered cannot exceed subjects 264 enrolled in 218079 study. But depemokimab pooled arm included 272 participants comprising 143 participants (217095) and 129 participants (218079) and for all pooled analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Week 52
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 10 | ||||||||||||
Statistical analysis description |
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)
|
||||||||||||
Comparison groups |
Pooled Placebo v Pooled Depemokimab
|
||||||||||||
Number of subjects included in analysis |
528
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
[16] | ||||||||||||
P-value |
= 0.146 | ||||||||||||
Method |
Cox Proportional Hazards Model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.713
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.453 | ||||||||||||
upper limit |
1.124 | ||||||||||||
| Notes [16] - Cox Proportional Hazards Model with covariates of treatment, baseline total endoscopic nasal polyps score, baseline nasal obstruction score (VRS), log(e) baseline blood eosinophil count, region, study and previous surgery for nasal polyps. |
|||||||||||||
|
|||||||||||||
End point title |
Change from Baseline in Asthma Control Questionnaire (ACQ-5) score at Week 52 | ||||||||||||
End point description |
The ACQ-5 is a 5-item questionnaire which enquires about the frequency and/or severity of asthma signs over the previous week (nocturnal awakening on waking in morning, activity limitation, & shortness of breath, wheeze). Each question is scored from 0 (no impairment) to 6 (total impairment). Higher scores indicate more limitations. Impact on asthma control in participants with an ACQ-5 score > 0.75 at baseline was assessed across replicate studies 217095 (2021-005037-16) and 218079 (2021-005055-36). Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value. FAS = randomized participants from study 217095 & 218079 excluding participants from 3 sites with GCP violation. Due to template limitations, the number of subjects (N) entered cannot exceed subjects 264 enrolled in 218079 study. But depemokimab pooled arm included 272 participants comprising 143 participants (217095 study) and 129 participants (218079 study) and for all pooled analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) and at Week 52
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 12 | ||||||||||||
Statistical analysis description |
The pooled statistical analyses will be performed using a Mixed Models Repeated Measures (MMRM) model with covariates of treatment group, baseline score, log(e) baseline blood eosinophil count, region, previous surgery for nasal polyps, study, visit and interaction terms for visit by baseline score and visit by treatment group.
|
||||||||||||
Comparison groups |
Pooled Depemokimab v Pooled Placebo
|
||||||||||||
Number of subjects included in analysis |
206
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.004 [17] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Adjusted mean difference | ||||||||||||
Point estimate |
-0.75
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.26 | ||||||||||||
upper limit |
-0.25 | ||||||||||||
| Notes [17] - Nominal significance (i.e., p<0.05 without multiplicity control) was achieved. However, statistical significance was not achieved due to a break in the multiplicity-controlled testing hierarchy. |
|||||||||||||
|
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Adverse events information
|
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Timeframe for reporting adverse events |
All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) until follow up at week 56.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 2 site with GCP violation. AEs were reported treatment-wise.
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.1
|
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Reporting groups
|
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Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received placebo SC injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance CRSwNP SOC treatment throughout the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Depemokimab
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received a 100 milligram (mg) dose of depemokimab subcutaneous (SC) injection once every 26 weeks (week 0 and week 26) over a treatment period for 52-weeks. Participants were to be maintained on their existing baseline maintenance CRSwNP standard of care (SOC) treatment throughout the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 3% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
09 Feb 2022 |
Amendment 1 |
||
26 Oct 2022 |
Amendment 2 |
||
17 Oct 2023 |
Amendment 3 |
||
12 Mar 2024 |
Amendment 4 |
||
26 Jun 2024 |
Amendment 5 |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
