Dupilumab in CRSsNP (Liberty CRSsNP ORION)

• Status: Recruiting
• Trial end date: 2024-05-30
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

Part A and B: To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan and sinus total symptom score (sTSS) compared to placebo

Secondary Objectives:

Part A

• To evaluate the efficacy of dupilumab as assessed by the reduction at Week 52 in sinus opacification on CT scan and total symptom score (sTSS) compared to placebo

• To evaluate the efficacy of dupilumab in improving CRSsNP symptoms at Weeks 24 and 52 compared to placebo

• To evaluate the effect of dupilumab on health related quality of life at Weeks 24 and 52 (HRQoL) compared to placebo

• To evaluate the effect of dupilumab on CRSsNP overall disease severity at Weeks 24 and 52 compared to placebo

• To evaluate the effect of dupilumab at Weeks 24 and 52 in the subgroups of participants with comorbid asthma compared to placebo

• To evaluate the ability of dupilumab to reduce the incidence of participants with CRSsNP worsening/acute sinusitis who require treatment with antibiotics, systemic corticosteroids (SCS) or sinus surgery compared to placebo

• To evaluate the effects of dupilumab on transcriptomic signatures associated with CRSsNP and type 2 inflammation

• To evaluate the effect of dupilumab in the subgroup of participants with screening blood eosinophils count ≥300 cells/mm3 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

Part B

• To evaluate the efficacy of dupilumab in improving CRSsNP symptoms at Week 24 compared to placebo in patients

• To evaluate the effect of dupilumab on health related quality of life (HRQoL) compared to placebo

• To evaluate the effect of dupilumab on CRSsNP overall disease severity compared to placebo

• To evaluate the effect of dupilumab in the subgroups of participants with comorbid asthma compared to placebo

• To evaluate the ability of dupilumab to reduce the incidence of participants with CRSsNP worsening/acute sinusitis who require treatment with antibiotics, SCS, or sinus surgery compared to placebo

• To evaluate the effects of dupilumab on transcriptomic signatures associated with CRSsNP and type 2 inflammation

• 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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals

Criteria

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:

• Prior sinonasal surgery for CRS,

• Treatment 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.

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.