A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps
Condition: Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
MeSH terms: Nasal Polyps; Polyps
Intervention: Dupilumab SAR231893 (REGN668); Placebo; Mometasone furoate 50 micrograms
Intervention description: Pharmaceutical form: Solution
Route of administration: Subcutaneous; Pharmaceutical form: Solution
Route of administration: Subcutaneous; Pharmaceutical form: Suspension (Nasal spray)
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: Double (Participant, Investigator)
Masking description: Dupilumab and placebo were provided in matching 2 milliliter (mL) pre-filled syringes. To protect the blind, each treatment kit was prepared such that the dupilumab dose and its corresponding placebo volume were identical and indistinguishable and were labelled with a treatment kit number.
Enrollment: 276.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Nasal polyposis, Chronic rhinosinusitis, Intranasal corticosteroids, Dupilumab, Human monoclonal antibody

Summary:

      Primary Objective:

      To evaluate the efficacy of dupilumab 300 milligram (mg) every 2 weeks (q2w) compared to
      placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal
      congestion/obstruction (NC) severity and endoscopic nasal polyp score (NPS) in participants
      with bilateral nasal polyposis (NP). In addition for Japan participants, reduction in
      computed tomography (CT) scan opacification of the sinuses was a coprimary objective.

      Secondary Objectives:

        -  To evaluate the efficacy of dupilumab in improving total symptoms score (TSS).

        -  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 Japan).

        -  To evaluate ability of dupilumab in reducing proportion of participants requiring
           treatment with systemic corticosteroids or NP surgery.

        -  To evaluate the effect of dupilumab on participant reported outcomes and health related
           quality of life outcome by sinonasal outcome test-22 (SNOT-22).

        -  To evaluate the effect of dupilumab in the subgroups of participants with prior surgery
           and co-morbid asthma (including non-steroid antiinflammatory drug [NSAID] exacerbated
           respiratory disease [ERD]).

        -  To evaluate residual effect in follow up.

        -  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 sinonasal polyposis that despite prior treatment with
             systemic corticosteroids (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 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 prior to Visit [V] 1) of nasal
             congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or
             3) at V1 and a weekly average severity of greater than 1 at the 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.

          -  Participants who were previously treated in dupilumab studies.

          -  Participants 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 (mAB) within 5 half-lives or within 6 months
             before V1 if the half-life was unknown.

          -  Anti-immunoglobulin E (IgE) 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.

          -  Initiated allergen immunotherapy within 3 months prior to V1 or planned to begin
             therapy or changed its dose during the run-in period or the randomized treatment
             period.

          -  Participants who undergone any intranasal and/or sinus surgery (including polypectomy)
             within 6 months prior to V1.

          -  Participants who had a sinonasal or sinus surgery changing the lateral wall structure
             of the nose making impossible the evaluation of NPS.

          -  Participants with conditions/concomitant diseases making them nonevaluable 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 in 1 second (FEV1) 50% or less (of
             predicted normal).

          -  Participants who received concomitant treatment prohibited in the study.

          -  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 (HBsAg) 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 planned 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.