Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of SAR231893/REGN668 Administered Subcutaneously Once Weekly for 12 Weeks in Patients With Persistent Moderate to Severe Eosinophilic Asthma Who Are Partially Controlled/Uncontrolled by Inhaled Corticosteroid Plus Long-acting beta2 Agonist Therapy
Brief Summary: Primary Objective:

To investigate the effects of Dupilumab (SAR231893/REGN668) administered subcutaneously (SC) once weekly (qw) for 12 weeks as compared to placebo on reducing the incidence of asthma exacerbation in participants with persistent moderate to severe eosinophilic asthma.

Secondary Objectives:

* To assess the safety and tolerability of Dupilumab administered SC qw for 12 weeks in participants with persistent moderate to severe eosinophilic asthma.
* To assess Dupilumab serum concentrations following qw SC dosing for 12 weeks in participants with persistent moderate to severe eosinophilic asthma.


Options:
A: Inclusion criteria:

Medical diagnosis of persistent asthma for at least 12 months whose:

* airway inflammation likely to be eosinophilic,
* asthma partially controlled or uncontrolled on ICS plus LABA therapy.
* On a stable dose of either Fluticasone/Salmeterol, Budesonide/Formoterol, Mometasone/Formoterol combination therapy for at least 1 month prior to screening.
* Signed an Informed Consent Form and Health Insurance Portability and Accountability Act (HIPAA) Authorization Form.

Exclusion criteria:

* Less than 18 years or greater than 65 years of age.
* Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further evaluation.
* Chronic obstructive pulmonary disease and/or other lung diseases impairing Pulmonary Function Tests.
* Beta-adrenergic receptor blockers required for any reason.
* Current smoker or cessation of smoking within the 6 months prior to screening.
* Previous smoking with a smoking history \>10 cigarette pack/years.
* Participation in another study within 6 months prior to screening if the study medication was an antibody or within 30 days prior to screening for all other study medications.
* Known or suspected non-compliance, alcohol or drug abuse.
* Inability to follow the procedures of the study (e.g, due to language problems, psychological disorders).
* Concomitant severe diseases or diseases for which the use of ICS or LABA were contraindicated.
* Known allergy to doxycycline or related compounds.
* Pregnancy or intention to become pregnant during the course of the study, breast feeding, or unwillingness to use a highly effective method of contraception throughout the study in women of childbearing potential.
* Recent history of a parasitic infection or travel to a parasitic endemic area within 6 months prior to screening.

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

* At least 12 years of age at study visit.
* Participants eligible for enrolment and entry into the study must meet the following definition of severe asthma, which is based on the definition of severe asthma described in the European Respiratory Society/ American Thoracic Society (ERS/ATS) Guidelines for severe asthma: Asthma which requires treatment with guideline suggested medications for Global Initiative for Asthma (GINA) steps 4-5 asthma for the previous year (i.e., at least 12 months).

Patients must be treated with high dose ICS PLUS at least one of the following: LABA, leukotriene modifier, theophylline, or continuous or near continuous systemic corticosteroid (i.e., maintenance systemic corticosteroid for ≥50% of the previous year).

SPECIAL CIRCUMSTANCE: If patient is on a fixed dose combination medication, then the maximum recommended dose of the ICS/LABA combination per local label is acceptable.

* 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. Participants must be able to read, comprehend, and write at a level sufficient to complete study related materials. A parent or legal guardian must provide informed consent for participants less than 18 years of age at study visit (or less than minimum age to be considered an adult per local laws).

Exclusion Criteria:

Participants who have participated in an interventional clinical trial for asthma within the past 12 months prior to Visit 1 (NOTE: subjects participating in an observational study where an investigational product or procedure is not administered will not be subject to this exclusion criteria)
C: Inclusion Criteria:

Severe persistent asthma with the following characteristics:

* Uncontrolled according to Global Initiative for Asthma (GINA) 2007 guidelines and at least 2 exacerbations having required systemic corticosteroid and/or at least 1 hospitalization or emergency room visit in the past year.
* Treated with high-dose inhaled corticosteroid (i.e. \> 1,000 µg beclometasone dipropionate equivalent per day) plus inhaled long-acting β2 agonist (with or without maintenance oral corticosteroid).
* Non-atopic, i.e. negative blood multiallergic testing and negative Aspergillus-specific IgE-radio allergosorbent blood test and negative skin prick tests to a battery of common aeroallergens

Exclusion Criteria:

* Current smokers or smoking history stopped for less than 3 years or \> 10 pack years.
* Asthma exacerbation during the 4 weeks prior to randomization.
* Active lung disease other than non-atopic asthma.
* Patients with an active cancer, a suspicion of cancer or any history of cancer with less than 5 disease free years.
* Pregnant or nursing (lactating) women.
* Treatment with omalizumab.

Other protocol-defined inclusion/exclusion criteria may apply
D: Inclusion Criteria:

* Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent, and an assent for subjects under 18 years of age, at Visit 0 (or Visit 1 if these Visits are conducted on the same day).
* MEA115666 or 201312 Study Participation: Participation (through the Follow Up/Exit Visit or Early Withdrawal) in either study with documented evidence of at least 6 months of continuous mepolizumab treatment prior to Visit 1. Continuous treatment with mepolizumab is defined as no more than 2 consecutive missed doses (no treatment gaps of more than 12 weeks \[84 days\] between any two doses).
* Current Anti-Asthma Therapy: Asthma is currently being treated with a controller medication and the subject has been on a controller medication for the past 12 weeks. Subjects will be expected to continue controller therapy for the duration of the study.
* Male or Eligible Female Subjects: A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, \> 45 years, in the absence of hormone replacement therapy.

OR Child bearing potential, has a negative pregnancy test at screening, and agrees to acceptable contraceptive methods approved in their local country, when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician) for the duration of the study and for 4 months after the last study drug administration.

A urine pregnancy test is required of all females of child-bearing potential at each scheduled study visit prior to the injection of study treatment, and at the Exit Visit, Early Withdrawal (EW) or Discontinuation of IP Visit.

* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* MEA115666 or 201312 IP Discontinuation: Subjects withdrawn from IP or withdrawn from study participation from either MEA115666 or 201312 for safety reasons.
* Health Status: Clinically significant deterioration in health status at the completion of participation or EW from either the MEA115666 or 201312 trials which in the opinion of the investigator would make the subject unsuitable for participation in this study.
* Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
* Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to:

known ejection fraction of \<30% OR severe heart failure meeting New York Heart Association Class IV classification OR hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.

* 12-Lead Electrocardiogram (ECG): ECG which has a clinically significant abnormality observed at the Screening Visit as determined by the investigator. Subjects with the following abnormalities are excluded from study participation: QT interval corrected for heart rate by Fridericia's formula (QTcF) \> 450 milliseconds (msec), or QTcF \>480 msec for subjects with Bundle Branch Block.
* Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Subjects that had localized carcinoma of the skin which was resected for cure will not be excluded).

Note for South Korea: Korean subjects with a diagnosis of malignancy within 5 years are excluded.

* Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than XOLAIR®) to treat inflammatory disease within 5 half-lives of Visit 1.

XOLAIR is a registered trademark of Genentech USA, Inc. and Novartis Pharmaceuticals Corporation.

* Adherence: Subjects who have known evidence of lack of adherence within studies MEA115666 or 201312 (less than 80%) to controller medications, scheduled study visits and/or ability to follow physician's recommendations.
* Smoking status: Current smokers
* Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

Answer: A