Study of Mepolizumab Autoinjector 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 an autoinjector.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 159.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: SB240563; Mepolizumab; self-administration; eosinophilic asthma; autoinjector

Summary:

      This study is aimed to assess the correct real-world use of an autoinjector for the repeat
      self-administration of mepolizumab SC, so to improve subject / physician convenience and to
      enable repeat dose self injection themselves or via caregivers. This Phase III study will be
      an open-label, single-arm, repeat-dose, multi-centre study of mepolizumab liquid drug product
      in autoinjector (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 158 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. (Subjects will be
             permitted to be enrolled without continuous high dose ICS providing the subject was
             receiving continuous ICS and the Investigator attest that the subject should have been
             treated with high dose ICS to mitigate the risk of exacerbations, or the subject has
             financial or tolerance issues that prevent the use of high-dose ICS. Such subjects
             should be discussed with GSK Medical Monitor prior to enrolment)

          -  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:

          -  Concurrent respiratory disease: 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.

          -  Eosinophilic diseases: 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 will also be excluded.

          -  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.

          -  Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus [HIV]),
             other than that explained by the use of corticosteroids taken as therapy for asthma.

          -  Other concurrent medical conditions: 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.

          -  Liver disease: 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).

          -  ECG assessment: QT interval corrected for heart rate by either Fridericia's or
             Bazett's formula (QTc[F] or QTc[B]) >=450 milliseconds (msec) or QTc(F) or QTc(B)
             >=480 msec for subjects with bundle branch block at Visit 1.

          -  Xolair: Subjects who have received omalizumab within 130 days of Visit 1.

          -  Other monoclonal antibodies not including mepolizumab: Subjects who have received any
             monoclonal antibody to treat inflammatory disease within 5 half-lives of Visit 1.

          -  Investigational medications: 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.

          -  Chemotherapy: Subjects who have received chemotherapy within 12 months prior to Visit
             1.

          -  Alcohol/substance abuse: A history (or suspected history) of alcohol misuse or
             substance abuse within 2 years prior to Visit 1.

          -  Hypersensitivity: Subjects with hypersensitivity to mepolizumab or to any of the
             excipients (sodium phosphate, citric acid, sucrose, ethylenediaminetetraacetic acid
             [EDTA], polysorbate 80).

          -  Adherence: Subjects who have known evidence of lack of adherence to controller
             medications and/or ability to follow physician's recommendations.