Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Persistent Asthma
Brief Summary: Primary Objective:

To evaluate the efficacy of dupilumab (SAR231893 / REGN668) in participants with persistent asthma.

Secondary Objectives:

* To evaluate the safety and tolerability of dupilumab.
* To evaluate the effect of dupilumab on improving participant-reported outcomes including health-related quality of life.
* To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies.


Options:
A: Inclusion Criteria:

* Diagnosis of asthma
* Age 18-70
* Current smoker
* Duration of symptoms \>1yr with stability for 4 weeks
* Able to maintain asthma without exacerbations during run in period
* Able to wean off other asthma medication

Exclusion Criteria:

* Ex-smokers or never smokers
* Planning to quit smoking during duration of trial
* Patients with unstable asthma
* Patients with current epilepsy, psychosis or history of significant atrial or ventricular tachyarrhythmia
* Corrected QT-interval greater than 450msec in women, 430msec in men
* Low potassium levels. If can be corrected then screening can continue with confirmation of normal levels prior to taking study medication
* Liver disease (ALT and/or AST levels 2 or more times ULN)
* Significant renal disease (Creatinine or urea levels 2 or more times ULN)
* Any previous severe adverse reactions to macrolides
* Patients who are known to have specific IgE sensitivity or skin test positivity to grass pollen and a history of worsening of asthma due to hay fever will not be recruited from mid May to the end of July
* Upper or lower respiratory tract infection in the 4 weeks prior to randomisation. Run in period can be prolonged in this situation to have 4 weeks with no respiratory infection prior to randomisation.
* Patients who require medications known to interact with azithromycin
* On other immunosuppressants or chronic antibiotics
* Weight less than 45kg
* Frequent asthma exacerbations (greater than 4) requiring oral corticosteroids in the year prior to randomisation
* Current or past diagnosis of allergic-bronchopulmonary-aspergillosis
* Pregnancy and breast feeding
* Mental impairment or language difficulties that makes informed consent not possible
B: Inclusion Criteria:

* 12-71 months of age.
* Recurrent significant wheezing in the past year (any of the following):

  * \>3 episodes, ≥1 of which was clinically significant\*; OR
  * \>2 clinically significant\* episodes; OR
  * \>4 months of daily controller therapy AND \>1 clinically significant\* episode.
  * \* Clinically significant episode: requiring any of the following: (1) systemic corticosteroids (oral or injectable), (2) unscheduled physician office visit, (3) ED visit, (4) urgent care visit, or (5) hospitalization.
* Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). If the subject needs varicella vaccine, this will be arranged with the primary care physician and must be received prior to randomization.
* Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

Participants who meet any of the following criteria are NOT eligible for enrollment, but may be re-enrolled if these exclusion criteria are resolved:

* \>4 courses of systemic corticosteroids in past 12 months.
* More than 1 hospitalization for wheezing illnesses within the preceding 12 months.
* Use of long-term controller medications for asthma, including inhaled corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline for more than 8 months (cumulative use) in the past 12 months.
* Current use of higher than step 2 NAEPP asthma guideline therapy (e.g. medium-high dose ICS alone or combination therapy of low-medium-high dose ICS + LABA, montelukast, theophylline or cromolyn). NOTE: children who have evidence of well-controlled symptoms immediately preceding study entry while receiving Step 2 controller therapy (presence of self-reported symptoms on average no more than 2 times per week and less than 2 nights per month of nocturnal awakenings, requiring albuterol, during the 4 weeks preceding visit 1) may be enrolled and will have their controller therapy discontinued upon study entry.
* Use of OCS in the past 2 weeks.
* Daily symptoms or \>2 nocturnal awakenings, requiring albuterol, on average in the last 2 weeks.
* Use of antibiotics in the past month.
* Current treatment with antibiotics for diagnosed sinus disease.
* Participation presently or in the past month in another investigational drug trial.
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before trial completion.
* Contraindication of use of systemic corticosteroids or azithromycin.
* Clinically relevant gastroesophageal reflux.
* Concurrent medical conditions other than asthma that are likely to require oral or injectable corticosteroids during the study.
* If receiving allergy shots, change in dose within the past 3 months.

Participants who meet any of the following criteria are NOT eligible for enrollment, and may not be re-enrolled:

* Gestation less than late preterm as defined as birth before 34 weeks gestational age.
* Presence of lung disease other than asthma, such as cystic fibrosis and BPD. Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed.
* Presence of other significant medical illnesses (cardiac, liver, gastrointestinal, endocrine) that would place the study subject at increased risk of participating in the study.
* Immunodeficiency disorders.
* History of respiratory failure requiring mechanical ventilation.
* History of hypoxic seizure.
* History of significant adverse reaction to any study medication ingredient.
* The child has significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year for age and gender. If a child plots less than the 10th percentile for age and gender, a growth chart for the previous year will be obtained from the child's primary care provider.
C: Inclusion Criteria:

* Participation in the COPSAC2010 cohort
* recurrent wheeze
* and others

Exclusion Criteria:

* Macrolide allergy
* Heart, liver or kidney disease.
* and others
D: Inclusion criteria:

-Adults and adolescent participants with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2014 Guidelines and the following criteria:

a) Existing treatment with medium to high dose ICS (≥250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) in combination with a second controller (eg, long-acting beta agonist, leukotriene receptor antagonist) for at least 3 months with a stable dose ≥1 month prior to Visit 1.

i) Note for Japan: for participants aged 18 years and older, ICS must be on ≥200 mcg of fluticasone propionate twice daily or equivalent; for participants aged 12 to 17 years, ICS must be ≥100 mcg of fluticasone propionate twice daily or equivalent).

ii) Participants requiring a third controller for their asthma will be considered eligible for this study, and it should also be used for at least 3 months with a stable dose ≥1 month prior to Visit 1.

Exclusion criteria:

* Participants \<12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (For those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who are ≥18 years of age).
* Weight is less than 30 kilograms.
* Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, etc) which may impair lung function.
* A participant who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to the Screening Visit up to and including the Baseline Visit).
* Evidence of lung disease(s) other than asthma, either clinical evidence or imaging (Chest X-ray, CT, MRI) within 12 months of Visit 1 or at the screening visit, as per local standard of care.
* Note for Japan: According to the request from the health authority, chest X-ray should be performed at screening visit if there is no chest imaging (Chest X-ray, computed tomography \[CT\], magnetic resonance imaging \[MRI\]) available within 3 months prior to screening to exclude participants with suspected active or untreated latent tuberculosis.
* Current smoker or cessation of smoking within 6 months prior to Visit 1.
* Previous smoker with a smoking history \>10 pack-years.
* Comorbid disease that might interfere with the evaluation of Investigational Medicinal Product.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Answer: D