Dupilumab in CRSsNP

NCT04678856 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC16723U1111-1246-75222020-003117-35
• Study Type: interventional
• Target: 71
• Locations: 13 countries
• Sites: 58

Brief Summary

Primary Objective: To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan in the dupilumab group only Secondary Objectives:

• To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on CT scan and sinus total symptom score (sTSS) compared to placebo
• To evaluate the safety and tolerability of dupilumab in CRSsNP patients compared to placebo
• To evaluate the pharmacokinetics (PK) of dupilumab in CRSsNP patients compared to placebo
• Assessment of immunogenicity to dupilumab over time compared to placebo

Conditions

Chronic Rhinosinusitis Without Nasal Polyps; Sinusitis; Chronic Sinusitis; Sinus Disorder; Respiratory Disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 24 in Opacification of Sinuses Assessed by Computed Tomography (CT) Scan Using the Lund Mackay (LMK) Score in Dupilumab Group

  The CT scan LMK staging system represented the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side). The extent of mucosal opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the ostiomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is therefore 12 per side; total score ranges from 0 (normal) to 24 (more opacified), corresponding to the sum of all sinuses and the ostiomeatal unit. Higher score indicated worse outcome. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.

  Baseline (Day 1) and Week 24

Secondary Outcomes (5)

• Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in Sinus Total Symptom Score (sTSS)

  Baseline (Day 1) and Week 24

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation

  From the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days

• Serum Concentration of Dupilumab Over Time

  Baseline (Day 1) and Weeks 12, 24 and 52

• Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab)

  Baseline (Day 1) and up to Week 52

Study Arms (2)

Part A and B: Dupilumab

EXPERIMENTAL

Participants received dupilumab 300 milligrams (mg) via SC injection q2w for up to 53.1 weeks.

Drug: Dupilumab SAR231893

Part A and B: Matching placebo

PLACEBO COMPARATOR

Participants received matching placebo via SC injection q2w for up to 53.2 weeks.

Drug: Placebo

Interventions

Dupilumab SAR231893 DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Part A and B: Dupilumab

Placebo DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Part A and B: Matching placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be at least 18 years of age at the time of signing the informed consent form (ICF).
• Participants must have bilateral inflammation of paranasal sinuses in CT scan with LMK ≥8 and bilateral ethmoid opacification before randomization.
• Participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by Visit 1.
• Participants must have ongoing symptoms of nasal congestion (NC)/obstruction at least 12 consecutive weeks before Visit 1 and a NC score of ≥ 2 at Visit 1 (day score) and Visit 2 (weekly average score).
• Participants must have sTSS (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score).
• Participants must have one of the 2 following features:
• Prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS,
• Treatment with systemic corticosteroids (SCS) therapy for CRS as defined by any dose and duration within the prior 2 years before screening (Visit 1) or intolerance/contraindication to SCS.

You may not qualify if:

• Participants with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at Visit 1 or with history of nasal polyposis etc., making them non-evaluable at Visit 1 or for the primary efficacy
• Nasal cavity malignant tumor and benign tumors.
• Forced expiratory volume (FEV1) ≤50% of predicted normal at Visit 1.
• Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis.
• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect participation in the study
• Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
• Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
• Known or suspected immunodeficiency
• History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period.
• History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients.
• Participants in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event.
• Participants who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period.
• Participants on unstable dose of intranasal corticosteroids (INCS) spray 4 weeks prior to Screening Visit (Visit1) and during screening period.
• Participants who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (58)

Sacramento Ear, Nose & Throat Site Number : 8400010

Roseville, California, 95661, United States

Location

Bensch Clinical Research LLC Site Number : 8400015

Stockton, California, 95207, United States

Location

Colorado Allergy and Asthma Centers, PC Site Number : 8400003

Denver, Colorado, 80230, United States

Location

University of Missouri Health System Site Number : 8400016

Columbia, Missouri, 65212, United States

Location

Nebraska Medical Research Institute Site Number : 8400007

Papillion, Nebraska, 68046, United States

Location

Optimed Research, LTD Site Number : 8400017

Columbus, Ohio, 43235, United States

Location

Vital Prospects Clinical Research Institute, P.C. Site Number : 8400004

Tulsa, Oklahoma, 74136, United States

Location

Essential Medical Research, LLC Site Number : 8400014

Tulsa, Oklahoma, 74137, United States

Location

Pharmaceutical Research & Consulting, Inc. Site Number : 8400006

Dallas, Texas, 75231, United States

Location

Alamo ENT Associates Site Number : 8400021

San Antonio, Texas, 78258, United States

Location

Eastern Virginia Medical School (EVMS) Medical Group - Otola Site Number : 8400009

Norfolk, Virginia, 23507, United States

Location

Investigational Site Number : 0320002

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number : 0320003

Ciudad Autonoma Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number : 0320001

Ciudad Autonoma Buenos Aires, C1425BEN, Argentina

Location

Investigational Site Number : 0560002

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number : 1240013

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Investigational Site Number : 1240010

Hamilton, Ontario, L8L 2X2, Canada

Location

Investigational Site Number : 1240007

Kingston, Ontario, K7L 2V7, Canada

Location

Investigational Site Number : 1240016

London, Ontario, N6A 4V2, Canada

Location

Investigational Site Number : 1240001

Montreal, Quebec, H2X 3E4, Canada

Location

Investigational Site Number : 1240012

Montreal, Quebec, H4A 3J1, Canada

Location

Investigational Site Number : 1240002

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Investigational Site Number : 1240005

Québec, G1V 4G5, Canada

Location

Investigational Site Number : 1240003

Québec, G1V 4W2, Canada

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8207257, Chile

Location

Investigational Site Number : 1560001

Beijing, 100730, China

Location

Investigational Site Number : 1560005

Changchun, 130021, China

Location

Investigational Site Number : 1560013

Changsha, 410013, China

Location

Investigational Site Number : 1560010

Chongqing, 400016, China

Location

Investigational Site Number : 1560006

Shanghai, 200065, China

Location

Investigational Site Number : 1560008

Yantai, 264000, China

Location

Investigational Site Number : 3480004

Budapest, 1115, Hungary

Location

Investigational Site Number : 3480001

Pécs, 7621, Hungary

Location

Investigational Site Number : 6200002

Aveiro, 3810-501, Portugal

Location

Investigational Site Number : 6200001

Guimarães, 4810-061, Portugal

Location

Investigational Site Number : 6200003

Matosinhos Municipality, 4464-513, Portugal

Location

Investigational Site Number : 6430005

Moscow, 121359, Russia

Location

Investigational Site Number : 6430002

Saint Petersburg, 197022, Russia

Location

Investigational Site Number : 6430003

Saint Petersburg, 197022, Russia

Location

Investigational Site Number : 6430001

Stavropol, 355020, Russia

Location

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 07061, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 135-710, South Korea

Location

Investigational Site Number : 7240002

Seville, Andalusia, 41009, Spain

Location

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number : 7240007

Santander, Cantabria, 39008, Spain

Location

Investigational Site Number : 7240004

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Investigational Site Number : 7240009

Madrid, Madrid, Comunidad de, 28027, Spain

Location

Investigational Site Number : 7240005

Madrid / Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number : 7240008

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240010

Madrid, 28034, Spain

Location

Investigational Site Number : 7520001

Stockholm, 171 76, Sweden

Location

Investigational Site Number : 8040005

Dnipro, 49006, Ukraine

Location

Investigational Site Number : 8040001

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number : 8040004

Kharkiv, 61166, Ukraine

Location

Investigational Site Number : 8040008

Kyiv, 01033, Ukraine

Location

Investigational Site Number : 8040002

Kyiv, 03680, Ukraine

Location

Investigational Site Number : 8040007

Kyiv, 04050, Ukraine

Location

Related Links

• EFC16723 Plain language Results Summary

MeSH Terms

Conditions

Sinusitis; Paranasal Sinus Diseases; Respiration Disorders

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610 ext 6#

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 22, 2020
• Study Start: December 2, 2020
• Primary Completion: November 14, 2023
• Study Completion: January 29, 2024
• Last Updated: February 10, 2025
• Results First Posted: December 18, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (6); US (11); ES (8); BE (2); HU (2); CA (9); PT (3); AR (3); RU (4); CL (1); KR (2); SE (1); UA (6)