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

A Single-arm, 52 Weeks, Phase 4 Study to Assess the Efficacy and Safety of Dupilumab in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP) Who Are Not Adequately Controlled With Existing Therapies

This was a Phase 4, open-label, single-arm, multicenter study to evaluate the efficacy and safety of dupilumab subcutaneous (SC) injection monotherapy in Japanese participants aged 18 or older with CRSwNP that is not adequately controlled with existing therapies.

Duration of study period (per participant):

• Screening Period (2 to 4 weeks)
• Intervention Period (up to 52 weeks±3 days)

Study Overview

• Status: Completed
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: Dupilumab SAR231893

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Japan, Japan
    • Investigational site JAPAN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants ≧18 years of age.

• Participants with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (SCS) anytime within the past 2 years; and/or had a medical contraindication / intolerance to SCS; and/or had prior surgery for NP at the screening visit, had:

  • An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity).
  • Ongoing symptoms (for at least 8 weeks prior to Visit [V] 1) of nasal congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at the time of enrollment (V2), and loss of smell, rhinorrhea (anterior/posterior).
• Participant's body weight > 30 kg at V1.
• Signed written informed consent.

Exclusion Criteria:

• Participant with conditions/concomitant diseases making them non evaluable at V1 or for the primary efficacy endpoint such as: Antrochoanal polyps; Nasal septal deviation that would occlude at least one nostril; Acute sinusitis, nasal infection or upper respiratory infection; Ongoing rhinitis medicamentosa; Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis; Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis;
• Participant with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil, etc).
• Participant diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before V1 or during screening
• Undergone any and/or sinus intranasal surgery within 6 months before V1.
• Participant who had participated in prior dupilumab clinical study or had been treated with commercially available dupilumab

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dupilumab; Dupilumab every 2 weeks (q2w). Dosing interval may be changed from q2w to q4w at week 24	Drug: Dupilumab SAR231893; Pharmaceutical form: solution for injection Route of administration: subcutaneous (SC); Other Names: REGN668

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With NPS Improvement From Baseline >=1 at 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.	Baseline (Day 1) and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Bilateral NPS at 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.	Baseline (Day 1) and Week 24
Change From Baseline in Nasal Congestion/Obstruction (NC) Symptom Severity Score Using the CRSwNP Nasal Symptom Diary at 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.	Baseline (Day 1) and Week 24
Change From Baseline in Opacification of Sinuses Assessed by Computerized Tomography (CT) Scan Using the Lund Mackay (LMK) Score at 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.	Baseline (Day 1) and Week 24
Change From Baseline in Total Symptom Score (TSS) at 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.	Baseline (Day 1) and Week 24
Change From Baseline in Loss of Smell Symptom Severity Score Using the Nasal Symptom Diary at 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.	Baseline (Day 1) and Week 24
Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis at 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.	Baseline (Day 1) and Week 24
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	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.	From Baseline (Day 1) up to Week 24

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): July 5, 2023

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 14, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Sinusitis; Nasal Polyps; Polyps
• Other Study ID Numbers: LPS16872

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes