Study of Mepolizumab Safety Syringe in Asthmatics
Condition: Asthma
MeSH terms: Asthma
Intervention: Mepolizumab
Intervention description: It is a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose EDTA and polysorbate 80 within a safety syringe.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: SB240563; self-administration; Mepolizumab; safety syringe; Eosinophilic asthma

Summary:

      This study is aimed to assess the correct real-world use of a safety syringe for the repeat
      self-administration of mepolizumab SC. This Phase III study will be an open-label,
      single-arm, repeat-dose, multi-centre study of mepolizumab liquid drug product in a safety
      syringe (100 milligrams [mg]) administered subcutaneously (SC) every 4 weeks (3 doses) in
      subjects with severe eosinophilic asthma. Subjects will receive 100 mg mepolizumab SC as a
      single injection that is self-administered in the thigh, abdomen or administered in the upper
      arm (caregiver only). Each subject will participate in the study for up to 18 weeks including
      pre-screening visit, a screening visit and a 12-week treatment period which concludes with
      end of study assessments (Visit 5) 4 weeks after the last dose of mepolizumab. Approximately
      55 Subjects will be enrolled in the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age: At least 12 years of age inclusive, at the time of signing the informed consent.
             For those countries where local regulations permit enrolment of adults only, subject
             recruitment will be restricted to those who are >=18 years of age.

          -  Asthma: A physician diagnosis of asthma for >=2 years that meets the National Heart,
             Lung and Blood Institute guidelines or Global Initiative for Asthma guidelines.

          -  Mepolizumab treatment:

             a. Not receiving mepolizumab treatment at Visit 1. These subjects must also meet
             following inclusion criteria related to eosinophilic asthma, inhaled corticosteroid,
             controller medication and exacerbation history):

          -  Eosinophilic asthma: A high likelihood of eosinophilic asthma as per the required
             'Continuation to Treatment'-criterion,

          -  Inhaled corticosteroid: A well-documented requirement for regular treatment with high
             dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without
             maintenance oral corticosteroids (OCS), for subjects >=18 years old, ICS dose must be
             >=880 micrograms (mcg)/day fluticasone propionate (FP) (ex-actuator) or equivalent
             daily, For ICS/long-acting-beta-2-agonist (LABA) combination preparations, the highest
             approved maintenance dose in the local country will meet this ICS criterion, for
             subjects >=12 to <=17 years old, ICS dose must be >=440 mcg/day FP (ex-actuator) or
             equivalent daily, for ICS/LABA combination preparations, the mid-strength approved
             maintenance dose in the local country will meet this ICS criterion.

          -  Controller medication: Current treatment with an additional controller medication,
             besides ICS, for at least 3 months or a documented failure in the past 12 months of an
             additional controller medication (e.g., LABA, leukotriene receptor antagonist [LTRA],
             or theophylline) for at least 3 successive months.

          -  Exacerbation history: Previously confirmed history of one or more exacerbations
             requiring treatment with systemic corticosteroid (CS) [intramuscular (IM),
             intravenous, or oral] in the 12 months prior to Visit 1, despite the use of high-dose
             ICS. For subjects receiving maintenance CS, the CS treatment for an exacerbation must
             have been a two-fold dose increase or greater.

        or, b. Receiving 100 mg SC mepolizumab administered for the treatment of severe
        eosinophilic asthma every 4 weeks for at least 12 weeks prior to Visit 1.

          -  Body weight: A minimum body weight >=40 kilograms (kg) at Visit 1

          -  Gender: Male or female. A female subject is eligible to participate if she is not
             pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG)]test),
             planning to become pregnant during the time of study participation (and up to 16 weeks
             after the last dose), not lactating, and at least one of the following conditions
             applies: Non-reproductive potential defined as: pre-menopausal females with documented
             tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up
             confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral
             oophorectomy, postmenopausal female, reproductive potential and agrees to follow
             highly effective methods for avoiding pregnancy in females of reproductive potential
             from 30 days prior to the first dose of study medication and until 16 weeks after the
             last dose of study medication and completion of the end of study/early withdrawal
             visit. The investigator is responsible for ensuring that subjects understand how to
             properly use these methods of contraception.

          -  Informed consent: Capable of giving signed informed consent.

        Exclusion Criteria

          -  Presence of a known pre-existing, clinically important lung condition other than
             asthma. This includes current infection, bronchiectasis, pulmonary fibrosis,
             bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis
             (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.

          -  Subjects with other conditions that could lead to elevated eosinophils such as
             Hypereosinophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic
             Esophagitis. Subjects with a known, pre-existing parasitic infestation within 6 months
             prior to Visit 1 are also to be excluded.

          -  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).

          -  A known immunodeficiency (e.g. human immunodeficiency virus - HIV), other than that
             explained by the use of corticosteroids taken as therapy for asthma.

          -  Subjects who have known, pre-existing, clinically significant cardiovascular,
             endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic,
             haematological or any other system abnormalities that are uncontrolled with standard
             treatment.

          -  Known, pre-existing, unstable liver disease (as defined by the presence of ascites,
             encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or
             persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception
             of Gilbert's syndrome or asymptomatic gallstones)

          -  QT interval corrected for heart rate by either Fridericia's or Bazett's formula
             QTc(F)/QTc(B) ≥450milliseconds (msec) or QTc(F)/QTc(B) ≥480 msec for subjects with
             Bundle Branch Block at Visit 1 confirmed by electrocardiogram (ECG).

          -  Subjects who have received omalizumab within 130 days of Visit 1.

          -  Subjects who have received any monoclonal antibody (other than Xolair) to treat
             inflammatory disease within 5 half-lives of Visit 1.

          -  Subjects who have received treatment with an investigational drug, other than
             mepolizumab within the past 30 days or five terminal phase half-lives of the drug
             whichever is longer, prior to visit 1 (this also includes investigational formulations
             of marketed products) or experimental anti-inflammatory drugs (non biologicals) in the
             past 3 months.

          -  Subjects who have received chemotherapy within 12 months prior to Visit 1.

          -  A history (or suspected history) of alcohol misuse or substance abuse within 2 years
             prior to Visit 1.

          -  Subjects with hypersensitivity to mepolizumab or to any of the excipients (sodium
             phosphate, citric acid, sucrose, ethylenediamine tetraacetic acid (EDTA), polysorbate
             80).

          -  Subjects who have known evidence of lack of adherence to controller medications and/or
             ability to follow physician's recommendations.