Open-label, Interventional, Cohort Study to Evaluate Long-term Safety of Dupilumab in Patients with Moderate to Severe Asthma who Completed the TRAVERSE-LTS12551Clinical Trial

Asthma is a chronic inflammatory disease of the airways characterized by airway
hyper-responsiveness, acute and chronic bronchoconstriction, airway edema, and
mucus plugging. The inflammatory component of asthma involves many cell types,
including mast cells, eosinophils, T-lymphocytes, neutrophils, epithelial
cells, and their biological products. For most asthma patients, a regimen of
controller therapy and reliever therapy provides adequate long-term control.
However, it is estimated that 5% to 10% of asthma patients have symptomatic
disease despite maximum recommended treatment with combinations of
anti-inflammatory and bronchodilator drugs (1).

The poor response of some patients with asthma may reflect the number of
cellular and molecular mechanisms operative in asthma. There is increasing
interest in distinct phenotypes because targeted therapy is more likely to be
successful in patients with similar underlying pathobiologic features (2).
Recent therapeutic approaches in asthma have been focused on trying to control
the Type 2 T-helper cell (Th2) response. Up-regulation of interleukin(IL)-4 and
IL-13 has been implicated as an important inflammatory component of asthma
disease progression.

Dupilumab, a fully human monoclonal antibody that binds specifically to the
shared interleukin-4 receptor alpha (IL-4R*) subunit of the IL-4 and IL 13
receptor complexes, is under development as a potential novel treatment for
asthma. Dupilumab inhibits IL-4 signaling via the Type I receptor, and both
IL-4 and IL-13 signaling through the Type II receptor. Dupilumab belongs to the
pharmacological class of immunomodulators, IL inhibitors.

The primary objective of this study is to describe the long-term safety of
dupilumab in the treatment of patients with moderate to severe asthma who
completed the previous asthma clinical trial, TRAVERSE-LTS12551.

The LPS15023 study is a Phase IIIb, open-label, interventional, outpatient,
prospective, multinational, multicenter, noncomparative, single-arm, safety
study.

Study patients will be subjected to the following particular
interventions/procedures or will have to undergo the below-stated physical
tests and fill in questionnaires:
-Subcutaneous injections
-Safety blood tests will be performed at a local laboratory; depending on the
site*s local laboratory
and facilities, either blood or urine may be assessed for pregnancy testing for
WOCBP.
-Blood samples for hematology are collected from patients during the treatment
period: Blood count (erythrocytes, hemoglobin,hematocrit, and leukocytes),
differential blood count (neutrophils, lymphocytes, monocytes, eosinophils, and
basophils), and platelets. --Blood samples for hematology are collected from
patients during the treatment period: Blood count (erythrocytes,
hemoglobin,hematocrit, and leukocytes), differential blood count (neutrophils,
lymphocytes, monocytes, eosinophils, and basophils), and platelets.
-For WOCBP only, blood or urine pregnancy test.
-Patients should fill out a home-dosing diary to document the administration of
study IMP/NIMP
medication.

- Hypersensitivity (allergic reactions; anaphylaxis represents the most severe
form thereof)
- Severe injection site reactions
- Infections (increased risk of parasitic infections).
* Infections or infestations that do not respond to medical treatment should
have study IMP
discontinued until the infection is resolved.
* For any opportunistic infection, such as TB or other infections whose nature
or course may
suggest an immunocompromised status (see Appendix E), patients must be
permanently
discontinued from IMP.