Dupilumab in CRSsNP

Sinusitis Clinical Trial

— Liberty 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04678856
• Other study ID #: EFC16723
• Secondary ID: U1111-1246-75222
• Status: Completed
• Phase: Phase 2
• Start date: December 2, 2020
• Est. completion date: January 29, 2024

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: January 29, 2024
• Est. primary completion date: November 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

• Patients 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.

• Patients 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.

• Patients 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.

• Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1.

• Patients 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 patient 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.

• Patients 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.

Related Conditions & MeSH terms

• Chronic Rhinosinusitis Without Nasal Polyps
• Chronic Sinusitis
• Nasal Polyps
• Respiration Disorders
• Respiratory Disorder
• Respiratory Tract Diseases
• Sinus Disorder
• Sinusitis

Intervention

Drug:
• Dupilumab SAR231893
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320002	Buenos Aires
Argentina	Investigational Site Number : 0320001	Ciudad Autonoma Buenos Aires
Argentina	Investigational Site Number : 0320003	Ciudad Autonoma Buenos Aires
Belgium	Investigational Site Number : 0560002	Gent
Belgium	Investigational Site Number : 0560001	Leuven
Canada	Investigational Site Number : 1240010	Hamilton	Ontario
Canada	Investigational Site Number : 1240007	Kingston	Ontario
Canada	Investigational Site Number : 1240016	London	Ontario
Canada	Investigational Site Number : 1240001	Montreal	Quebec
Canada	Investigational Site Number : 1240012	Montreal	Quebec
Canada	Investigational Site Number : 1240003	Quebec
Canada	Investigational Site Number : 1240005	Quebec
Canada	Investigational Site Number : 1240002	Trois-Rivieres	Quebec
Canada	Investigational Site Number : 1240013	Vancouver	British Columbia
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
China	Investigational Site Number : 1560001	Beijing
China	Investigational Site Number : 1560005	Changchun
China	Investigational Site Number : 1560013	Changsha
China	Investigational Site Number : 1560010	Chongqing
China	Investigational Site Number : 1560006	Shanghai
China	Investigational Site Number : 1560008	Yantai
Hungary	Investigational Site Number : 3480004	Budapest
Hungary	Investigational Site Number : 3480001	Pécs
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100003	Seoul	Seoul-teukbyeolsi
Portugal	Investigational Site Number : 6200002	Aveiro
Portugal	Investigational Site Number : 6200001	Guimarães
Portugal	Investigational Site Number : 6200003	Matosinhos
Russian Federation	Investigational Site Number : 6430005	Moscow
Russian Federation	Investigational Site Number : 6430002	St-Petersburg
Russian Federation	Investigational Site Number : 6430003	St-Petersburg
Russian Federation	Investigational Site Number : 6430001	Stavropol
Spain	Investigational Site Number : 7240001	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Jerez de la Frontera	Cádiz
Spain	Investigational Site Number : 7240009	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240010	Madrid
Spain	Investigational Site Number : 7240005	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240008	Pamplona	Navarra
Spain	Investigational Site Number : 7240007	Santander	Cantabria
Spain	Investigational Site Number : 7240002	Sevilla	Andalucia
Sweden	Investigational Site Number : 7520001	Stockholm
Ukraine	Investigational Site Number : 8040005	Dnipro
Ukraine	Investigational Site Number : 8040001	Ivano-Frankivsk
Ukraine	Investigational Site Number : 8040004	Kharkiv
Ukraine	Investigational Site Number : 8040002	Kyiv
Ukraine	Investigational Site Number : 8040007	Kyiv
Ukraine	Investigational Site Number : 8040008	Kyiv
United States	University of Missouri Health System Site Number : 8400016	Columbia	Missouri
United States	Optimed Research, LTD Site Number : 8400017	Columbus	Ohio
United States	Pharmaceutical Research & Consulting, Inc. Site Number : 8400006	Dallas	Texas
United States	Colorado Allergy and Asthma Centers, PC Site Number : 8400003	Denver	Colorado
United States	Eastern Virginia Medical School (EVMS) Medical Group - Otola Site Number : 8400009	Norfolk	Virginia
United States	Nebraska Medical Research Institute Site Number : 8400007	Papillion	Nebraska
United States	Sacramento Ear, Nose & Throat Site Number : 8400010	Roseville	California
United States	Alamo ENT Associates Site Number : 8400021	San Antonio	Texas
United States	Bensch Clinical Research LLC Site Number : 8400015	Stockton	California
United States	Essential Medical Research, LLC Site Number : 8400014	Tulsa	Oklahoma
United States	Vital Prospects Clinical Research Institute, P.C. Site Number : 8400004	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Chile,  China,  Hungary,  Korea, Republic of,  Portugal,  Russian Federation,  Spain,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to Week 24 in opacification of sinuses assessed by CT scan using the Lund Mackay (LMK) score in the dupilumab group only	LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification).	Baseline to Week 24
Secondary	Change from baseline to Week 24 in opacification of sinuses assessed by CT scan using the LMK score	LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification).	Baseline to Week 24
Secondary	Change from baseline to Week 24 in sTSS	The sTSS is a composite score derived from the following individual items: NC, anterior/posterior rhinorrhea, and facial pain/pressure. The total score ranges from 0-9. Higher scores on sTSS indicate greater overall symptom severity.	Baseline to Week 24
Secondary	Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), and TEAEs leading to treatment discontinuation	Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), and TEAEs leading to treatment discontinuation.	Baseline to Week 64
Secondary	Dupilumab concentration in serum	Dupilumab concentration in serum.	Baseline to Week 52
Secondary	Incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time	Incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time.	Baseline to Week 64