Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
Condition: Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
MeSH terms: Nasal Polyps; Polyps
Intervention: Dupilumab SAR231893 (REGN668); Placebo; Mometasone furoate nasal spray
Intervention description: Pharmaceutical form: Solution
Route of administration: Subcutaneous; Pharmaceutical form: Solution
Route of administration: Subcutaneous; Pharmaceutical form: Suspension
Route of administration: Intranasal
Intervention MeSH terms: Mometasone Furoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 448.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To evaluate the efficacy of dupilumab 300 mg every 2 weeks (q2w) compared to placebo on a
      background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion
      (NC)/obstruction severity and endoscopic nasal polyp score (NPS) in participants with
      bilateral nasal polyps (NP). In addition for Japanese participants, reduction in computed
      tomography (CT) scan opacification of the sinuses was a co-primary objective.

      Secondary Objectives:

        -  To evaluate the efficacy of dupilumab in improving total symptoms score.

        -  To evaluate the efficacy of dupilumab in improving sense of smell.

        -  To evaluate the efficacy of dupilumab in reducing CT scan opacification of the sinuses
           (primary objective for Japanese participants).

        -  To evaluate ability of dupilumab in reducing proportion of participants who required
           treatment with systemic corticosteroids (SCS) or surgery for NP.

        -  To evaluate the effect of dupilumab on participant reported outcomes and health related
           quality of life.

        -  To evaluate the efficacy of dupilumab 300 mg q2w up to Week 52.

        -  To evaluate the efficacy of dupilumab 300 mg q2w up to Week 24 followed by 300 mg every
           4 weeks (q4w) up to Week 52.

        -  To evaluate the effect of dupilumab in the subgroups of participants with prior surgery
           and comorbid asthma including non-steroid anti-inflammatory drug exacerbated respiratory
           disease.

        -  To evaluate the safety of dupilumab in participants with bilateral NP.

        -  To evaluate functional dupilumab concentrations (systemic exposure) and incidence of
           treatment emergent anti-drug antibodies.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with bilateral sino-nasal polyposis that despite prior treatment with SCS
             anytime within the past 2 years; and/or had a medical contraindication/intolerance to
             SCS; and/or had prior surgery for NP at the screening visit, had:

          -  An endoscopic bilateral NPS at Visit 1 (V1) of at least 5 out of a maximum score of 8
             (with a minimum score of 2 in each nasal cavity).

          -  Ongoing symptoms (for at least 8 weeks before V1) of NC/blockage/obstruction with
             moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity
             of greater than 1 at time of randomization (V2), and another symptom such as loss of
             smell, rhinorrhea (anterior/posterior).

          -  Signed written informed consent.

        Exclusion criteria:

          -  Participants <18 years of age.

          -  Participant who had been previously treated in dupilumab studies.

          -  Participant who had taken:

               -  Biologic therapy/ systemic immunosuppressant to treat inflammatory disease or
                  autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary
                  biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) within
                  2 months before V1 or 5 half-lives, whichever was longer.

               -  Any experimental monoclonal antibody within 5 half-lives or within 6 months
                  before V1 if the half-life was unknown.

               -  Anti-immunoglobulin E therapy (omalizumab) within 130 days prior to V1.

               -  Participants who received leukotriene antagonists/modifiers at V1 unless they
                  were on a continuous treatment for at least 30 days prior to V1.

          -  Initiation of allergen immunotherapy within 3 months prior to V1 or a plan to begin
             therapy or change its dose during the run-in period or the randomized treatment
             period.

          -  Participants who underwent any and/or sinus surgery (including polypectomy) within 6
             months before V1.

          -  Participants who had a sino-nasal or sinus surgery changing the lateral wall structure
             of the nose making impossible the evaluation of NPS.

          -  Participants with conditions/concomitant diseases making them non evaluable at V1 or
             for the primary efficacy endpoint such as:

               -  Antrochoanal polyps,

               -  Nasal septal deviation that would occlude at least one nostril,

               -  Acute sinusitis, nasal infection or upper respiratory infection,

               -  Ongoing rhinitis medicamentosa,

               -  Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with
                  polyangiitis (Wegener's granulomatosis),Young's syndrome, Kartagener's syndrome
                  or other dyskinetic ciliary syndromes, concomitant cystic fibrosis,

               -  Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis.

          -  Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood
             boil etc.).

          -  Participants with forced expiratory volume 50% or less (of predicted normal).

          -  Participants who received concomitant treatment prohibited in the study.

          -  Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit.

          -  Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit.

          -  History of human immunodeficiency virus (HIV) infection or positive HIV serology at
             screening.

          -  Positive with hepatitis B surface antigen or hepatitis C antibody at the screening
             visit.

          -  Active chronic or acute infection requiring systemic treatment within 2 weeks before
             the baseline visit.

          -  Known or suspected history of immunosuppression.

          -  Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed
             during the study.

          -  Women unwilling to use adequate birth control, if of reproductive potential and
             sexually active.

        The above information was not intended to contain all considerations relevant to a
        Participant's potential participation in a clinical trial.