- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT01508936
Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma
A 16-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) Treatment in Patients With Moderate to Severe Asthma
A tanulmány áttekintése
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 3. fázis
Kapcsolatok és helyek
Tanulmányi helyek
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Alabama
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Birmingham, Alabama, Egyesült Államok
- Investigational Site 861
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Homewood, Alabama, Egyesült Államok
- Investigational Site 842
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Jasper, Alabama, Egyesült Államok
- Investigational Site 887
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Arizona
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Tucson, Arizona, Egyesült Államok
- Investigational Site 809
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Tucson, Arizona, Egyesült Államok
- Investigational Site 892
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Arkansas
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Little Rock, Arkansas, Egyesült Államok
- Investigational Site 846
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California
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Anaheim, California, Egyesült Államok
- Investigational Site 828
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Fresno, California, Egyesült Államok
- Investigational Site 900
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Huntington Beach, California, Egyesült Államok
- Investigational Site 862
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Los Angeles, California, Egyesült Államok
- Investigational Site 852
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Los Angeles, California, Egyesült Államok
- Investigational Site 909
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Newport Beach, California, Egyesült Államok
- Investigational Site 864
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Rancho Mirage, California, Egyesült Államok
- Investigational Site 812
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Riverside, California, Egyesült Államok
- Investigational Site 808
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Sacramento, California, Egyesült Államok
- Investigational Site 804
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Colorado
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Centennial, Colorado, Egyesült Államok
- Investigational Site 837
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Denver, Colorado, Egyesült Államok
- Investigational Site 851
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Wheat Ridge, Colorado, Egyesült Államok
- Investigational Site 832
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Florida
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Jacksonville, Florida, Egyesült Államok
- Investigational Site 855
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Miami, Florida, Egyesült Államok
- Investigational Site 865
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Miami, Florida, Egyesült Államok
- Investigational Site 881
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Georgia
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Albany, Georgia, Egyesült Államok
- Investigational Site 805
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Stockbridge, Georgia, Egyesült Államok
- Investigational Site 870
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Illinois
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Chicago, Illinois, Egyesült Államok
- Investigational Site 816
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Shiloh, Illinois, Egyesült Államok
- Investigational Site 824
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Indiana
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Evansville, Indiana, Egyesült Államok
- Investigational Site 883
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Fort Wayne, Indiana, Egyesült Államok
- Investigational Site 878
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Kansas
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Lenexa, Kansas, Egyesült Államok
- Investigational Site 820
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Kentucky
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Owensboro, Kentucky, Egyesült Államok
- Investigational Site 873
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Louisiana
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Lafayette, Louisiana, Egyesült Államok
- Investigational Site 801
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Mandeville, Louisiana, Egyesült Államok
- Investigational Site 877
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Maryland
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White Marsh, Maryland, Egyesült Államok
- Investigational Site 875
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Massachusetts
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Fall River, Massachusetts, Egyesült Államok
- Investigational Site 871
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North Dartmouth, Massachusetts, Egyesült Államok
- Investigational Site 834
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Michigan
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Troy, Michigan, Egyesült Államok
- Investigational Site 889
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Missouri
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Rolla, Missouri, Egyesült Államok
- Investigational Site 838
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St. Louis, Missouri, Egyesült Államok
- Investigational Site 818
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St. Louis, Missouri, Egyesült Államok
- Investigational Site 841
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New Mexico
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Albuquerque, New Mexico, Egyesült Államok
- Investigational Site 857
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New York
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Newburgh, New York, Egyesült Államok
- Investigational Site 819
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North Carolina
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Charlotte, North Carolina, Egyesült Államok
- Investigational Site 844
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Ohio
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Middleburg Heights, Ohio, Egyesült Államok
- Investigational Site 845
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Oklahoma
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Tulsa, Oklahoma, Egyesült Államok
- Investigational Site 810
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Oregon
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Ashland, Oregon, Egyesült Államok
- Investigational Site 859
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Portland, Oregon, Egyesült Államok
- Investigational Site 859
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Pennsylvania
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Jenkintown, Pennsylvania, Egyesült Államok
- Investigational Site 854
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Rhode Island
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Providence, Rhode Island, Egyesült Államok
- Investigational Site 843
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South Carolina
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Florence, South Carolina, Egyesült Államok
- Investigational Site 802
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Orangeburg, South Carolina, Egyesült Államok
- Investigational Site 814
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Spartanburg, South Carolina, Egyesült Államok
- Investigational Site 821
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Spartanburg, South Carolina, Egyesült Államok
- Investigational Site 829
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Tennessee
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Knoxville, Tennessee, Egyesült Államok
- Investigational Site 850
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Nashville, Tennessee, Egyesült Államok
- Investigational Site 803
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Texas
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Dallas, Texas, Egyesült Államok
- Investigational Site 880
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Dickinson, Texas, Egyesült Államok
- Investigational Site 858
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Live Oak, Texas, Egyesült Államok
- Investigational Site 869
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Plano, Texas, Egyesült Államok
- Investigational Site 879
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Utah
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Salt Lake City, Utah, Egyesült Államok
- Investigational Site 847
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West Jordan, Utah, Egyesült Államok
- Investigational Site 876
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Virginia
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Fairfax, Virginia, Egyesült Államok
- Investigational Site 840
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Richmond, Virginia, Egyesült Államok
- Investigational Site 836
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Washington
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Seattle, Washington, Egyesült Államok
- Investigational Site 867
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Spokane, Washington, Egyesült Államok
- Investigational Site 833
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Vancouver, Washington, Egyesült Államok
- Investigational Site 904
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Wisconsin
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Greenfield, Wisconsin, Egyesült Államok
- Investigational Site 806
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LaCrosse, Wisconsin, Egyesült Államok
- Investigational Site 823
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Inclusion criteria:
Patients are included in the study if all of the following criteria are met:
- The patient is a man or woman, 18 through 65 years of age, with a diagnosis of asthma.
- The patient has an ACQ score of at least 1.5.
- At screening, the patient has airway reversibility of at least 12% to beta-agonist administration.
- The patient is currently taking fluticasone at a dosage of at least 440 µg daily (or equivalent). Patients' baseline asthma therapy regimens (including but not limited to inhaled corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, cromolyn) must be stable for 30 days before screening and continue without dosage changes throughout study.
- Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative beta-human chorionic gonadotropin (ßHCG) result for a pregnancy test at screening (serum) and baseline (urine).
- Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected).
- Written informed consent is obtained.
- The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, electrocardiogram (ECG) evaluation, serum chemistry, hematology, urinalysis, and serology.
- The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and be willing to return to the clinic for the follow-up evaluation as specified in this protocol.
Exclusion Criteria:
Patients are excluded from participating in this study if 1 or more of the following criteria are met:
- The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis).
- The patient has a clinically meaningful comorbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
- The patient has known hypereosinophilic syndrome (HES).
- The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
- The patient has a history of use of systemic immunosuppressive or immunomodulating agents (anti-immunoglobulin E [anti-IgE] mAb, methotrexate, cyclosporin, interferon-α, anti-tumor necrosis factor mAb, or omalizumab) within 6 months prior to study entry (randomization).
- The patient is currently using or has used systemic corticosteroids (includes use of oral corticosteroids) within 30 days prior to the screening visit.
- The patient is expected to be poorly compliant with study drug administration, study procedures, or visits.
- The patient has any aggravating factors that are inadequately controlled, and thus would aggravate asthma symptoms (eg, gastroesophageal reflux disease).
- The patient has participated in any investigative drug or device study within 30 days prior to screening.
- The patient has participated in any investigative biologics study within 90 days prior to screening.
- The patient has previously received reslizumab or other anti-hIL-5 mAbs (eg, mepolizumab).
- The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
- The patient has a current infection or disease that may preclude assessment of asthma.
- The patient has a history of concurrent immunodeficiency (human immunodeficiency, acquired immunodeficiency syndrome, or congenital immunodeficiency).
- The patient is suspected of current drug or alcohol abuse as specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
- The patient has presence of or suspected parasitic infestation/infection.
- Patients may not have received any live attenuated vaccine within the 12-week period before study entry.
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Négyszeres
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Placebo Comparator: Placebo
Placebo intravenous injection every 4 weeks for a total of 4 doses.
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Matching placebo administered by intravenous (iv) infusion by qualified study personnel every 4 weeks for 16 weeks (for a total of 4 doses).
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Kísérleti: Reslizumab 3.0 mg/kg
Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
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Reslizumab administered at a dosage of 3.0 mg/kg by intravenous (iv) infusion by qualified study personnel every 4 weeks for 16 weeks (for a total of 4 doses).
Más nevek:
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in Full Analysis Set
Időkeret: Baseline (Day 1), Week 16
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FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry. Data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10^9/liter) by treatment group. |
Baseline (Day 1), Week 16
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, 16
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FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control. During study (Weeks 4, 8, 12 and 16) average value was calculated using a mixed effects model for repeated measures (MMRM) with treatment (reslizumab or placebo), blood eosinophil count at baseline, and the interaction of treatment and eosinophil count as a random effect. |
Baseline (Day 1), Weeks 4, 8, 12, 16
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Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, 16
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The ACQ score was measured using the ACQ-7. Six questions are-self assessments; the seventh item is the result of the patient's % predicted FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6). A score of 0 indicates good asthma control; higher scores indicate increasingly poorer asthma control. Negative change from baseline scores indicate improvement in asthma control. During study (Weeks 4, 8, 12 and 16) average value was calculated from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, history of asthma exacerbation in the previous year, height, baseline value, and sex as fixed factors, and patient as a random effect. |
Baseline (Day 1), Weeks 4, 8, 12, 16
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in FEV1 Subpopulation
Időkeret: Baseline (Day 1), Week 16
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FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry. As with the primary outcome, data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10^9/liter) by treatment group. However the FEV1 subpopulation includes participants with more impaired lung function (% predicted FEV1 <85% at baseline). |
Baseline (Day 1), Week 16
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Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, and 16
|
FEV1 is a standard measurement of air movement in the lungs of patients with asthma.
It is the volume of air expired in the first second of a forced expiration.
Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both.
FEV1 was measured using forced expiratory air spirometry.
Positive change from baseline scores indicate improvement in asthma control.
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Baseline (Day 1), Weeks 4, 8, 12, and 16
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Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, and 16
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The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the patient's predicted FEV based on a similar population without asthma.
Percent predicted lung function values were transcribed directly from the lung function report to the CRF, without any calculation by Teva.
Positive change from baseline scores indicate improvement in asthma control.
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Baseline (Day 1), Weeks 4, 8, 12, and 16
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Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, and 16
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The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.
FV was measured using forced expiratory air spirometry.
Positive change from baseline scores indicate improvement in asthma control.
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Baseline (Day 1), Weeks 4, 8, 12, and 16
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Change From Baseline in the Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%) at Weeks 4, 8, 12, and 16
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, and 16
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The FEF25%-75% is the forced expiratory flow at 25% to 75% of the forced vital capacity.
FEF25%-75% was measured using forced expiratory air spirometry.
Positive change from baseline scores indicate improvement in asthma control.
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Baseline (Day 1), Weeks 4, 8, 12, and 16
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Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16
Időkeret: Baseline (Day -2 to 1), Weeks 4, 8, 12, and 16
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SABA are used for quick relief of asthma symptoms.
The number of times SABA therapy was used was assessed using 3 day recall at scheduled visits.
Participants were asked to recall whether SABAs were used within 3 days of the scheduled visit and, if so, how many puffs were used.
Daily use was the average of those 3 days.
Negative change from baseline scores indicate improvement in asthma control.
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Baseline (Day -2 to 1), Weeks 4, 8, 12, and 16
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Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint
Időkeret: Baseline (Day 1), Weeks 4, 8, 12, 16, Follow-up (Week 28)
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Blood eosinophil counts were measured using a standard complete blood count with differential blood test at each scheduled visit.
Follow-up was performed approximately 12 weeks after the 16 week treatment period.
Endpoint is the last post-baseline assessment.
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Baseline (Day 1), Weeks 4, 8, 12, 16, Follow-up (Week 28)
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Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16
Időkeret: Baseline (Day 1), Weeks 4, 8, 12 and 16
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The ACQ score was measured using the ACQ-7.
Six questions are self-assessments; the seventh item is the result of the patient's % predicted FEV1 measurement.
Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6).
A score of 0 indicates good asthma control; higher scores indicate increasingly poorer asthma control.
Negative change from baseline scores indicate improvement in asthma control.
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Baseline (Day 1), Weeks 4, 8, 12 and 16
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Participants With Treatment-Emergent Adverse Events
Időkeret: Day 1 to Week 28
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An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug.
Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities.
Relation of AE to treatment was determined by the investigator.
Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
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Day 1 to Week 28
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Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
Időkeret: Week 4 to Week 16
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Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values during any of the lab tests conducted during the treatment period. Significance criteria:
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Week 4 to Week 16
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Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
Időkeret: Week 4 to Week 28
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Data represents participants with potentially clinically significant (PCS) vital sign values during any of the treatment period exams. Significance criteria
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Week 4 to Week 28
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Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Electrocardiogram (ECG) Abnormalities
Időkeret: Week 16 or endpoint
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Counts represent the number of participants with potentially clinically significant ECG abnormalities as assessed by the investigator.
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Week 16 or endpoint
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Participants With a Positive Anti-Reslizumab Antibody Status During Study
Időkeret: Screening (Week -3), Weeks 8 and 16
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Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the experimental treatment arm. Blood samples were collected for determination of ADAs before study drug infusion at screening, weeks 8 and 16 or early withdrawal. Serum samples from patients who were treated with reslizumab were analyzed for ADA by Teva (Teva Biopharmaceuticals USA, Rockville, MD) using a validated homogeneous solution-based bridging enzyme-linked immunosorbent assay (ELISA). Endpoint =week 16 or early withdrawal. Counts represent the total number of participants at each time point with a positive immunogenicity test, and not 'new' participants with a positive test. An overall status of positive includes participants who had a positive ADA at any time point. |
Screening (Week -3), Weeks 8 and 16
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Együttműködők és nyomozók
Nyomozók
- Tanulmányi igazgató: Global Respiratory Clinical Research, M.D., Sponsor's Medical Expert
Publikációk és hasznos linkek
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Becslés)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Becslés)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
- Légúti betegségek
- Immunrendszeri betegségek
- Tüdőbetegségek
- Túlérzékenység, azonnali
- Hematológiai betegségek
- Bronchiális betegségek
- Tüdőbetegségek, obstruktív
- Légúti túlérzékenység
- Túlérzékenység
- Leukocita rendellenességek
- Eozinofília
- Hipereozinofil szindróma
- Asztma
- Tüdő eozinofília
- Asztmaellenes szerek
- Légzőrendszeri szerek
- Reslizumab
Egyéb vizsgálati azonosító számok
- C38072/3084
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .