Allergic Asthma
Conditions
Brief summary
This research is being done to test whether differences in blood cells at baseline (start of the study) can be used to predict how well omalizumab will work in a patient. Omalizumab (Xolair) is a drug approved by the U.S. Food and Drug Administration (FDA) to treat asthma. Studies show that omalizumab improves the symptoms of asthma but some people experience better improvement than others.
Detailed description
From a therapeutic perspective, the study will determine whether changes in the peripheral blood basophil response to crosslinking anti-IgE Ab during treatment with omalizumab predicts the clinical efficacy of treatment with the drug. Secondary outcomes measures would focus on whether the starting level of anti-IgE-mediated histamine release, or the changes syk expression or its starting level would be sufficient to predict the clinical outcome. The study is a single-site trial to evaluate the utility of baseline basophil measures to predict the efficacy of subcutaneously administered omalizumab as an add-on therapy for the treatment of adult patients 18-75 years old who have been diagnosed with moderate to severe asthma according to current approved guidelines. Patients will be treated with omalizumab according to the standard FDA approved dosing table for a period of 16 weeks.
Interventions
DRUGOmalizumab
Sponsors
Novartis Pharmaceuticals
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with moderate-to-severe asthma; male and females aged 18-75 who are symptomatic despite treatment with inhaled corticosteroids if they also had an asthma duration \> 1 year. * Positive blood testing to at least one common allergen (including must mite, D. F. and D. P., cockroach, dog or cat) * Serum IgE within the bounds of the dosing table (\>30 IU/ml to \< 700 IU/ml) * Reversibility of \> 12% within 30 minutes after administration of albuterol or history of reversibility in past or history of positive methacholine in past * Baseline Forced expiratory volume (FEV1) of \> 0% and \< 80% of predicted * Treatment with 400 to 800 ug day of beclomethasone dipropionate or its equivalent. * Patients must be willing to give written informed consent and be able to adhere to dose and visit schedules and meet trial requirements. * Patients will be excluded if they have prior sensitivity to omalizumab, and acute respiratory tract infection prior to or during the run-in period, or a need for regular B-agonist use.
Exclusion criteria
* Treatment with an investigational agent within 30 days of screening * Previously treated with omalizumab within a year prior to screening * Treatment 1 month prior to screening with: hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, intravenous immunoglobulin G, and plasmapheresis * Clinically relevant laboratory anomalies at screening including individuals with reduced hematocrit (\<32%), White Blood Cell (WBC) count (2400/microliter), platelet count (\< 75000/microliter), and increased creatinine (\> 141.4 micromolar/L), or aminotransferase (AST) (\>100 IU/L). * Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy, or bleeding disorder. * History of any medical condition that is unstable * Inability to comply with study and follow-up procedures * Patients may not take systemic corticosteroids within 2 weeks prior to screening\\ * Women of childbearing potential who are pregnant or nursing mothers, or who are of childbearing potential (post-menarche) and are not practicing an acceptable form of contraception ( as determined by the site investigator) * Individuals with body weight less than 30 kg or greater than 150 kg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Peripheral Blood Basophil Response to Crosslinking Anti-IgE Ab | baseline and 26 weeks | Data will be analyzed for the fold change in the in vitro anti-IgE-mediated histamine release response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Syk Expression | baseline and 26 weeks | Change in syk expression. Syk is a signaling molecule that is the first downstream event in IgE receptor activation of basophils. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Active
Omalizumab | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 4 |
Baseline characteristics
| Characteristic | Omalizumab |
|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 10 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Changes in the Peripheral Blood Basophil Response to Crosslinking Anti-IgE Ab
Data will be analyzed for the fold change in the in vitro anti-IgE-mediated histamine release response
Time frame: baseline and 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Changes in the Peripheral Blood Basophil Response to Crosslinking Anti-IgE Ab | 7.8 Fold change in basophil Syk expression | Standard Deviation 4.8 |
Secondary
Changes in Syk Expression
Change in syk expression. Syk is a signaling molecule that is the first downstream event in IgE receptor activation of basophils.
Time frame: baseline and 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab | Changes in Syk Expression | 2.3 fold change | Standard Deviation 0.4 |