Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, 52-week, Placebo Controlled Efficacy and Safety Study of Dupilumab, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
Brief 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.


Options:
A: Inclusion Criteria:

* Adults aged 18-75
* Severe bilateral nasal polyps with average endoscopic score of at least 5
* Blood eosinophil count of at least 300/ul at screening
* At least 1000mg prednisone (or equivalent) over the previous 12 months to control symptoms
* At least one prior nasal surgical polypectomy
* Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
* Female subjects: Women of childbearing potential (WOCBP) must use an effective form of birth control (confirmed by the Investigator). Effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective Intra-uterine device (IUD) intrauterine device/ levonogestrel Intrauterine system (IUS), Depo-Provera(tm) injections, oral contraceptive, and Evra Patch(tm) or Nuvaring(tm). WOCBP must agree to use effective method of birth control, as defined above, from enrolment, throughout the study duration and within 16 weeks after last dose of IP, and have negative serum pregnancy test result on Visit 0.
* Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of visit -1 without an alternative medical cause. The following age-specific requirements apply:
* Women \<50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
* Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
* All male subjects who are sexually active must agree to use an acceptable method of contraception (condom with or without spermicide, vasectomy) from Visit 0 until 16 weeks after their last dose.

Exclusion Criteria:

* Immunosuppression other than oral steroids in the past 3 months
* Allergen immunotherapy build up phase in the past 3 months
* Symptomatic or untreated life threatening cardiopulmonary disorders
* Subjects who are febrile (≥38°C; ≥100.4°F);
* History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable was obtained. Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained.
* A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.
* Pregnant or nursing
* If female and of child-bearing potential, positive pregnancy test or failure to adhere to acceptable method of contraception (with \<1% failure rate) during the study and for four months after the study.
* Receipt of any investigational non biologic within 30 days or 5 half-lives prior to visit 0, whichever is longer.
* A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
* Any other medical illness that precludes study involvement
* Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to be enrolled.
* Patients who are currently receiving or have previously received benralizumab or any other type of anti-interleukin therapy (i.e. mepolizumab, reslizumab, lebrikizumab etc.) within the last 4 months or 5 half-lives whichever is longer.
* History of anaphylaxis to any biologic therapy or vaccine.
* Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
* Receipt of live attenuated vaccines within 30 days of starting the study drug.
B: 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.
C: 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.
D: Inclusion Criteria:

* The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma.
* The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening.
* The patient has a current blood eosinophil level of at least 400/μl.
* The patient has airway reversibility of at least 12% to beta-agonist administration.
* The patient has an ACQ score of at least 1.5 at the screening and baseline (before the 1st dose of study drug) visits.
* The patient is taking inhaled fluticasone at a dosage of at least 440 μg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, oral corticosteroids up to a maximum of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout study.
* All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ß-human chorionic gonadotropin \[ß-HCG\]) at screening (serum) and baseline (urine).
* Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
* Written informed consent is obtained. Patients 12 through 17 years old must provide assent.
* The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis.

  * Other criteria apply; please contact the investigator for more information.

Exclusion Criteria:

* The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
* The patient has known hypereosinophilic syndrome.
* The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded.
* The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
* The patient is using systemic immunosuppressive or immunomodulating or other biologic agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor \[anti TNF\] mAb) within 6 months prior to screening.
* The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab).
* The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).
* The patient has participated in any investigative drug or device study within 30 days prior to screening.
* The patient has participated in any investigative biologics study within 6 months prior to screening.
* Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control.

  * Other criteria apply; please contact the investigator for more information.

Answer: C