Dupilumab in CRSsNP

Phase 1

• Conditions: Chronic rhinosinusitis without nasal polyposis; MedDRA version: 20.1Level: PTClassification code 10009137Term: Chronic sinusitisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2020-003117-35-HU
• Lead Sponsor: Sanofi-aventis Recherche & Développement

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-11
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 437

Inclusion Criteria

- Part A only: Participant must be at least 18 years of age at the time of signing the informed consent form (ICF).
- Part B only: Participant must be at least 12 years of age (or the minimum legal age for adolescents in the country of the investigational site) at the time of signing the 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:
oPrior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS,
oComorbid asthma,
oTreatment with 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.
- For Part B only: participants who have a blood eosinophil count =300 cells/mm3 at Screening
- Body weight =30 kg.
Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 371
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 44

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
- 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 the patient’s 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 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:
oBiologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
oAny investigational mAb within 5 half-lives prior to Visit 1
oAnti-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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified