Clinical trial NCT04678856: Dupilumab in CRSsNP
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Uncontrolled, Chronic Rhinosinusitis Without Nasal Polyposis (CRSsNP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Rhinosinusitis Without Nasal Polyps
Sinusitis
Chronic Sinusitis
Sinus Disorder
Respiratory Disorder
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-12-22
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: The duration of study for each participant will include 2-4 weeks of screening period, 24-52 weeks randomized investigational medicinal product (IMP) intervention period and 12 weeks of follow-up period.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Participants who have taken:

  * Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
  * Any investigational mAb within 5 half-lives prior to Visit 1
  * Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1.
* Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1
* Leukotriene antagonists/modifiers unless participant is on a continuous treatment for at least 30 days prior to Visit 1.
* Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period.
* Participants received SCS during screening period (between Visit 1 and Visit 2).
* Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).

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

Primary outcomes:
measure: 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
timeFrame: Baseline (Day 1) and Week 24
Secondary outcomes:
measure: Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
timeFrame: Baseline (Day 1) and Week 24
measure: Change From Baseline to Week 24 in Sinus Total Symptom Score (sTSS)
timeFrame: Baseline (Day 1) and Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation
timeFrame: 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
measure: Serum Concentration of Dupilumab Over Time
timeFrame: Baseline (Day 1) and Weeks 12, 24 and 52
measure: Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab)
timeFrame: Baseline (Day 1) and up to Week 52
Other outcomes:
Locations:
city: Roseville
country: United States
facility: Sacramento Ear, Nose & Throat Site Number : 8400010
state: California
city: Stockton
country: United States
facility: Bensch Clinical Research LLC Site Number : 8400015
state: California
city: Denver
country: United States
facility: Colorado Allergy and Asthma Centers, PC Site Number : 8400003
state: Colorado
city: Columbia
country: United States
facility: University of Missouri Health System Site Number : 8400016
state: Missouri
city: Papillion
country: United States
facility: Nebraska Medical Research Institute Site Number : 8400007
state: Nebraska
city: Columbus
country: United States
facility: Optimed Research, LTD Site Number : 8400017
state: Ohio
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C. Site Number : 8400004
state: Oklahoma
city: Tulsa
country: United States
facility: Essential Medical Research, LLC Site Number : 8400014
state: Oklahoma
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting, Inc. Site Number : 8400006
state: Texas
city: San Antonio
country: United States
facility: Alamo ENT Associates Site Number : 8400021
state: Texas
city: Norfolk
country: United States
facility: Eastern Virginia Medical School (EVMS) Medical Group - Otola Site Number : 8400009
state: Virginia
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Gent
country: Belgium
facility: Investigational Site Number : 0560002
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240013
state: British Columbia
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240010
state: Ontario
city: Kingston
country: Canada
facility: Investigational Site Number : 1240007
state: Ontario
city: London
country: Canada
facility: Investigational Site Number : 1240016
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number : 1240012
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240005
city: Quebec
country: Canada
facility: Investigational Site Number : 1240003
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Beijing
country: China
facility: Investigational Site Number : 1560001
city: Changchun
country: China
facility: Investigational Site Number : 1560005
city: Changsha
country: China
facility: Investigational Site Number : 1560013
city: Chongqing
country: China
facility: Investigational Site Number : 1560010
city: Shanghai
country: China
facility: Investigational Site Number : 1560006
city: Yantai
country: China
facility: Investigational Site Number : 1560008
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480004
city: Pécs
country: Hungary
facility: Investigational Site Number : 3480001
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Aveiro
country: Portugal
facility: Investigational Site Number : 6200002
city: Guimarães
country: Portugal
facility: Investigational Site Number : 6200001
city: Matosinhos
country: Portugal
facility: Investigational Site Number : 6200003
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430005
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430002
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430003
city: Stavropol
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240002
state: Andalucia
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Investigational Site Number : 7240007
state: Cantabria
city: Jerez de la Frontera
country: Spain
facility: Investigational Site Number : 7240004
state: Cádiz
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240005
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240009
state: Madrid, Comunidad De
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240008
state: Navarra
city: Madrid
country: Spain
facility: Investigational Site Number : 7240010
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520001
city: Dnipro
country: Ukraine
facility: Investigational Site Number : 8040005
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number : 8040001
city: Kharkiv
country: Ukraine
facility: Investigational Site Number : 8040004
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040008
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040002
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040007
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: