Clinical trial NCT02937168: An Imaging Study Using PET/CT to Characterize the Effect of Intravenous Reslizumab on Airway Inflammation
Official title: Distribution of Eosinophils in Asthma After Reslizumab (DEAR). A 7-Week, Placebo-Controlled, Double-Blinded, Parallel-Group, Imaging Study Using Positron Emission Tomography/Computer Tomography (PET/CT) to Characterize the Effect of Intravenous Reslizumab on Airway Inflammation in Patients With Eosinophilic Asthma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-18
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Part 1: Average Global Lung Glycolysis (GLG) at Baseline (Day 1)
timeFrame: Baseline (Day 1) of Part 1
measure: Part 1: Average Global Lung Glycolysis (GLG) at Day 8
timeFrame: Day 8
measure: Part 2: Change From Baseline to Week 4 in GLG
timeFrame: Baseline, Week 4
measure: Part 2: Change From Baseline to Week 4 in Lung Parenchyma (LP) SUV Mean
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Part 2: Change From Baseline to Week 4 in Blood Eosinophil Counts
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 4 in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 4 in Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 4 in Asthma Quality of Life Questionnaire (AQLQ) Score
timeFrame: Baseline, Week 4
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 21 days
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Teva Investigational Site 13808
state: New Jersey
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: