An Imaging Study Using PET/CT to Characterize the Effect of Intravenous Reslizumab on Airway Inflammation
Condition: Asthma
MeSH terms: Asthma; Inflammation
Intervention: Reslizumab; Fludeoxyglucose F 18 (FDG); Placebo
Intervention description: Reslizumab will be administered as per the dose and schedule specified in the arm.; FDG will be administered by IV infusion prior to each PET/CT scan.; Placebo matching to reslizumab will be administered as per the schedule specified in the arm.
Intervention MeSH terms: Reslizumab; Fluorodeoxyglucose F18
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is an exploratory study with the following primary objectives: 1) to establish that
      PET/CT of the lung can reliably distinguish healthy, non-asthmatic participants from
      participants with severe asthma and an eosinophilic phenotype and 2) to examine the utility
      of PET/CT for demonstrating that reslizumab produces a reduction in lung inflammation in
      participants with severe asthma and an eosinophilic phenotype .
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, 18 through 50 years of age.

          -  Females that are either surgically sterile, are 2 years postmenopausal, or have a
             negative pregnancy test at screening.

          -  Females of childbearing potential (not surgically sterile or 2 years postmenopausal),
             have to use a medically accepted method of contraception and have to agree to continue
             to use of this method for the duration of the study and for 5 months after study drug
             administration.

          -  Participants with less that 10-pack year history of smoking.

          -  Have a previous diagnosis of asthma.

          -  Participants taking inhaled fluticasone at a dosage of at least 440 micrograms (mcg)
             daily, or equivalent.

          -  The participant's baseline asthma therapy must be stable for 30 days prior to
             screening and judged by their treating physician to be able to continue without dosage
             changes throughout the study.

          -  Participants with a blood eosinophil level of at least 400 cells/microliter (cells/μL)
             at screening. Participants with a blood eosinophil level below 400 cells/μL will be
             given 2 additional screening opportunities to determine blood eosinophil levels.

               -  Additional criteria apply; please contact the investigator for more information.

        Exclusion Criteria:

          -  Participants requiring treatment with oral, intramuscular, or IV corticosteroids
             within 6 weeks of the Part 1 baseline visit for an asthma exacerbation.

          -  Participants with any other confounding underlying lung disorder including but not
             limited to: bronchiectasis, chronic obstructive pulmonary disorder, smoking greater
             than or equal to (≥)10 pack year history, pulmonary fibrosis, emphysema, cystic
             fibrosis, and lung cancer.

          -  Participants diagnosed with diabetes mellitus.

          -  Participants with pulmonary conditions and blood eosinophilia other than eosinophilic
             asthma.

          -  Participants with clinically meaningful comorbidity that can interfere with the study
             schedule or procedures, or compromise the participant's safety.

          -  Participants that are current smokers (that is, have smoked within the last 12 months
             prior to screening).

          -  Participants using systemic immunosuppressive, immunomodulating, or other biologic
             agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin,
             interferon-α, or anti-tumor necrosis factor mAb) within 6 months prior to screening.
             Participants whose treatment with anti-IgE mAb therapy (omalizumab) is considered
             ineffective by their physician may be included as potential participants when:

               1. The omalizumab (Xolair) therapy has been discontinued.

               2. The participant's blood eosinophil level meets inclusion criteria.

          -  Participants who have previously received an anti-hIL-5 mAb (for example, reslizumab,
             mepolizumab [Nucala]) or anti-IL-5 receptor mAb (eg, benralizumab). Participants whose
             treatment with mepolizumab or benralizumab is considered ineffective by their
             physician may be included as potential participants when:

               1. The mepolizumab or benralizumab therapy has been discontinued.

               2. The participant's blood eosinophil level meets inclusion criteria.

          -  Participants who had concurrent infection or disease that may preclude assessment of
             active asthma.

          -  Participants with a history of concurrent immunodeficiency (human immunodeficiency
             virus or acquired immunodeficiency syndrome or congenital immunodeficiency).

          -  Participants that had an active parasitic infection within 6 months prior to
             screening.

          -  Participants with any disorder that may interfere with drug absorption, distribution,
             metabolism, or excretion (including gastrointestinal surgery).

          -  Known hypersensitivity to study drug or to FDG/contrast agents

          -  Treatment with metformin.

          -  Compromised renal function.

               -  Additional criteria apply; please contact the investigator for more information.