Trial Outcomes & Findings for Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52) (NCT NCT05049122)

NCT ID: NCT05049122

Last Updated: 2025-09-11

Results Overview

The NPS was the sum of right and left nostril scores as assessed by central video recordings of nasal endoscopy (NE). For each nostril, NPS was graded based on polyp size: Grade 0:No polyps; Grade 1:Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; Grade 2:Polyps reaching below the lower border of the middle turbinate; Grade 3:Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; Grade 4:Large polyps causing complete obstruction of the inferior nasal cavity. Score ranged from 0-8; higher scores indicated more severity. The baseline value was defined as the last available value before first study treatment administration.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 25 participants
• Primary outcome timeframe: Baseline (Day 1) and Week 24
• Results posted on: 2025-09-11

Participant Flow

The study was conducted at 9 centers in Japan. A total of 30 participants were screened from 22 Oct 2021 to 22 Jun 2022 of which 5 were screen failures due to not meeting eligibility criteria.

The study consisted of a screening period (up to 4 weeks) and a treatment period (up to 52 weeks). A total of 25 participants were enrolled in this study. The study duration for each participant was up to 56 weeks.

Participant milestones

Measure	Dupilumab 300 Milligrams (mg) Participants received dupilumab 300 mg every 2 weeks (q2w) up to Week 24. Participants with stable disease (nasal polyp score \[NPS\] improvement from baseline to both Weeks 16 and 24 of greater than or equal to \[\>=\]2 points) at Week 24 received dupilumab 300 mg every 4 weeks (q4w) after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.
Overall Study STARTED	25
Overall Study Participants Who Completed the Week 24 Study Treatment Period as Per Protocol	23
Overall Study Participants Who Were Considered Stable Condition at Week 24	3
Overall Study q4w Regimen Participants (Stable Condition)Who Completed Week 52 Study Treatment Period Per Protocol	3
Overall Study Participants Who Continued the q2w Regimen	20
Overall Study The q2w Regimen Participants Who Completed the Week 52 Treatment Period as Per Protocol	19
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Dupilumab 300 Milligrams (mg) Participants received dupilumab 300 mg every 2 weeks (q2w) up to Week 24. Participants with stable disease (nasal polyp score \[NPS\] improvement from baseline to both Weeks 16 and 24 of greater than or equal to \[\>=\]2 points) at Week 24 received dupilumab 300 mg every 4 weeks (q4w) after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.
Overall Study Adverse event not related to Coronavirus Diesease-2019	1
Overall Study Participant moved	1
Overall Study At the direction of the doctor	1

Baseline Characteristics

Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52)

Baseline characteristics by cohort

Measure	Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.
Age, Continuous	53.4 years STANDARD_DEVIATION 13.56 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The Per protocol (PP) analysis set consisted of all participants in modified intent-to-treat (mITT) set (Enrolled population with chronic rhinosinusitis with nasal polyp \[CRSwNP\] allocated to study treatment administered at least 1 dose of study treatment) and who did not receive intranasal corticosteroids (INCS) up to Week 24

The NPS was the sum of right and left nostril scores as assessed by central video recordings of nasal endoscopy (NE). For each nostril, NPS was graded based on polyp size: Grade 0:No polyps; Grade 1:Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; Grade 2:Polyps reaching below the lower border of the middle turbinate; Grade 3:Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; Grade 4:Large polyps causing complete obstruction of the inferior nasal cavity. Score ranged from 0-8; higher scores indicated more severity. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Percentage of Participants With NPS Improvement From Baseline >=1 at Week 24

92.0 percentage of participants Interval 72.5 to 98.6

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The PP analysis set consisted of all participants in mITT allocated to study treatment administered at least 1 dose of study treatment, and who did not receive INCS up to Week 24.

The NPS was the sum of right and left nostril scores as assessed by central video recordings of NE. For each nostril, NPS was graded based on polyp size: Grade 0:No polyps; Grade 1:Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; Grade 2:Polyps reaching below the lower border of the middle turbinate; Grade 3:Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; Grade 4:Large polyps causing complete obstruction of the inferior nasal cavity. Score ranged from 0-8; higher scores indicated more severity. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Change From Baseline in Bilateral NPS at Week 24

-2.4 score on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The PP analysis set consisted of all participants in mITT allocated to study treatment administered at least 1 dose of study treatment, and who did not receive INCS up to Week 24.

The NC was assessed by the participant using a diary on a daily basis from Visit 1 and throughout the study on a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). It was scored as a reflective score (evaluation of symptom severity over the past 24 hours) by the participants. The score ranged from 0-3; higher scores indicated more severity. The baseline value was defined as the last available value before first study treatment administration. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Change From Baseline in Nasal Congestion/Obstruction (NC) Symptom Severity Score Using the CRSwNP Nasal Symptom Diary at Week 24

-1.58 score on a scale Standard Error 0.213

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The PP analysis set consisted of all participants in mITT allocated to study treatment administered at least 1 dose of study treatment, and who did not receive INCS up to Week 24.

The LMK system is based on localization 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, and frontal sinus on each side. The osteomeatal complex (OC) was graded as 0 = not occluded or 2 = occluded. The total score was the sum of scores from each side and ranged from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Change From Baseline in Opacification of Sinuses Assessed by Computerized Tomography (CT) Scan Using the Lund Mackay (LMK) Score at Week 24

-5.6 score on a scale Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The PP analysis set consisted of all participants in mITT allocated to study treatment administered at least 1 dose of study treatment, and who did not receive INCS up to Week 24.

The TSS was the sum of participant-assessed nasal symptom scores for nasal congestion and/or obstruction, decreased/loss of sense of smell and rhinorrhea (average of the non-missing anterior/posterior nasal discharge). On a daily basis from Visit 1 and throughout the study, participants used a diary to respond to the morning individual rhinosinusitis symptom questions using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Change From Baseline in Total Symptom Score (TSS) at Week 24

-4.20 score on a scale Standard Error 0.582

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The PP analysis set consisted of all participants in mITT allocated to study treatment administered at least 1 dose of study treatment, and who did not receive INCS up to Week 24.

The severity of loss of smell was reported by the participants using the nasal symptom diary with a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), higher score indicated more severe symptoms. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Change From Baseline in Loss of Smell Symptom Severity Score Using the Nasal Symptom Diary at Week 24

-1.37 score on a scale Standard Error 0.258

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The PP analysis set consisted of all participants in mITT allocated to study treatment administered at least 1 dose of study treatment, and who did not receive INCS up to Week 24.

The VAS for rhinosinusitis was used to evaluate the total disease severity. Rhinosinusitis was divided into mild, moderate and severe based on total severity VAS score (0 to 10 centimeters [cm] where mild: VAS 0 to 3; moderate: VAS >3 to 7 and severe: VAS >7 to 10). The participants were asked to indicate on a VAS the answer to the question: "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worst thinkable troublesome), where higher score indicated worse disease. For participants who discontinued for other reasons, missing data were imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

Outcome measures

Measure

Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.

Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis at Week 24

-5.41 cm Standard Error 0.622

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to Week 24

Population: The Safety analysis set consisted of all participants allocated to study treatment and administered at least 1 dose of study treatment before Week 24.

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TE period which was defined as the period from the time of first dose of study treatment until the last visit in the study. Serious adverse events (SAE) were defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Data reported is till the end of 24-week treatment period.

Outcome measures

Measure	Dupilumab 300 mg n=25 Participants Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation at the End of 24-Week Treatment Period Any TEAE	11 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation at the End of 24-Week Treatment Period Any TESAE	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation at the End of 24-Week Treatment Period Any TEAE leading to treatment discontinuation	0 Participants

Adverse Events

Dupilumab 300 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dupilumab 300 mg n=25 participants at risk Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.
Psychiatric disorders Suicide Attempt	4.0% 1/25 • Number of events 1 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.
Infections and infestations Vestibular neuronitis	4.0% 1/25 • Number of events 1 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.

Other adverse events

Measure	Dupilumab 300 mg n=25 participants at risk Participants received dupilumab 300 mg q2w up to Week 24. Participants with stable disease (NPS improvement from baseline to both Weeks 16 and 24 of \>=2 points) at Week 24 received dupilumab 300 mg q4w after Week 24 up to Week 48 and those who could not achieve stable disease at Week 24 continued to receive dupilumab 300 mg q2w after Week 24 up to Week 50. All participants were followed up to Week 52.
Infections and infestations Covid-19	20.0% 5/25 • Number of events 5 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.
Infections and infestations Nasopharyngitis	8.0% 2/25 • Number of events 2 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.
Immune system disorders Seasonal Allergy	8.0% 2/25 • Number of events 2 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.
General disorders Injection Site Erythema	8.0% 2/25 • Number of events 6 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.
General disorders Pyrexia	8.0% 2/25 • Number of events 3 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.
Injury, poisoning and procedural complications Accidental Overdose	8.0% 2/25 • Number of events 2 • From first treatment administration up to Week 52 The Safety analysis set consisted of all participants allocated to study treatment administered at least 1 dose of study treatment during the intervention period.

Additional Information

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