Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma

Eosinophilic Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01508936
• Other study ID #: C38072/3084
• Status: Completed
• Phase: Phase 3
• First received: January 3, 2012
• Last updated: May 8, 2014
• Start date: January 2012
• Est. completion date: October 2013

Study information

• Verified date: May 2014
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to characterize the efficacy of reslizumab treatment, at a dosage of 3.0 milligrams per kilogram (mg/kg) every 4 weeks for a total of 4 doses, in improving pulmonary function in relation to baseline blood eosinophil levels in patients with moderate to severe asthma, as assessed by the change from baseline to week 16 in forced expiratory volume in 1 second (FEV1).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 510
• Est. completion date: October 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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-a, 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Eosinophilic Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• Reslizumab
Reslizumab will be administered to patients 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).
• Matching Placebo
Matching placebo will be administered every 4 weeks for 16 weeks.

Locations

Country	Name	City	State
United States	Investigational Site 805	Albany	Georgia
United States	Investigational Site 857	Albuquerque	New Mexico
United States	Investigational Site 828	Anaheim	California
United States	Investigational Site 859	Ashland	Oregon
United States	Investigational Site 861	Birmingham	Alabama
United States	Investigational Site 837	Centennial	Colorado
United States	Investigational Site 844	Charlotte	North Carolina
United States	Investigational Site 816	Chicago	Illinois
United States	Investigational Site 880	Dallas	Texas
United States	Investigational Site 851	Denver	Colorado
United States	Investigational Site 858	Dickinson	Texas
United States	Investigational Site 883	Evansville	Indiana
United States	Investigational Site 840	Fairfax	Virginia
United States	Investigational Site 871	Fall River	Massachusetts
United States	Investigational Site 802	Florence	South Carolina
United States	Investigational Site 878	Fort Wayne	Indiana
United States	Investigational Site 900	Fresno	California
United States	Investigational Site 806	Greenfield	Wisconsin
United States	Investigational Site 842	Homewood	Alabama
United States	Investigational Site 862	Huntington Beach	California
United States	Investigational Site 855	Jacksonville	Florida
United States	Investigational Site 887	Jasper	Alabama
United States	Investigational Site 854	Jenkintown	Pennsylvania
United States	Investigational Site 850	Knoxville	Tennessee
United States	Investigational Site 823	LaCrosse	Wisconsin
United States	Investigational Site 801	Lafayette	Louisiana
United States	Investigational Site 820	Lenexa	Kansas
United States	Investigational Site 846	Little Rock	Arkansas
United States	Investigational Site 869	Live Oak	Texas
United States	Investigational Site 852	Los Angeles	California
United States	Investigational Site 909	Los Angeles	California
United States	Investigational Site 877	Mandeville	Louisiana
United States	Investigational Site 865	Miami	Florida
United States	Investigational Site 881	Miami	Florida
United States	Investigational Site 845	Middleburg Heights	Ohio
United States	Investigational Site 803	Nashville	Tennessee
United States	Investigational Site 819	Newburgh	New York
United States	Investigational Site 864	Newport Beach	California
United States	Investigational Site 834	North Dartmouth	Massachusetts
United States	Investigational Site 814	Orangeburg	South Carolina
United States	Investigational Site 873	Owensboro	Kentucky
United States	Investigational Site 879	Plano	Texas
United States	Investigational Site 859	Portland	Oregon
United States	Investigational Site 843	Providence	Rhode Island
United States	Investigational Site 812	Rancho Mirage	California
United States	Investigational Site 836	Richmond	Virginia
United States	Investigational Site 808	Riverside	California
United States	Investigational Site 838	Rolla	Missouri
United States	Investigational Site 804	Sacramento	California
United States	Investigational Site 847	Salt Lake City	Utah
United States	Investigational Site 867	Seattle	Washington
United States	Investigational Site 824	Shiloh	Illinois
United States	Investigational Site 821	Spartanburg	South Carolina
United States	Investigational Site 829	Spartanburg	South Carolina
United States	Investigational Site 833	Spokane	Washington
United States	Investigational Site 818	St. Louis	Missouri
United States	Investigational Site 841	St. Louis	Missouri
United States	Investigational Site 870	Stockbridge	Georgia
United States	Investigational Site 889	Troy	Michigan
United States	Investigational Site 809	Tucson	Arizona
United States	Investigational Site 892	Tucson	Arizona
United States	Investigational Site 810	Tulsa	Oklahoma
United States	Investigational Site 904	Vancouver	Washington
United States	Investigational Site 876	West Jordan	Utah
United States	Investigational Site 832	Wheat Ridge	Colorado
United States	Investigational Site 875	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Forced Expiratory Volume in 1 second (FEV1)	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 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.	Baseline and Week 16	No
Secondary	Change in FEV1	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 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.	Baseline and Week 4	No
Secondary	Change in FEV1	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 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.	Baseline and Week 8	No
Secondary	Change in FEV1	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 will be measured using forced expiratory air spirometry. Standard methods for this measurement are widely accepted in clinical practice.	Baseline and Week 12	No
Secondary	Change in Percent Predicted FEV1	The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the forced vital capacity (FVC).	Baseline and Week 4	No
Secondary	Change in Percent Predicted FEV1	The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the FVC.	Baseline and Week 8	No
Secondary	Change in Percent Predicted FEV1	The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the FVC.	Baseline and Week 12	No
Secondary	Change in Percent Predicted FEV1	The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the FVC.	Baseline and Week 16	No
Secondary	Change in Forced Vital Capacity (FVC)	The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.	Baseline and Week 4	No
Secondary	Change in Forced Vital Capacity (FVC)	The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.	Baseline and Week 8	No
Secondary	Change in Forced Vital Capacity (FVC)	The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.	Baseline and Week 12	No
Secondary	Change in Forced Vital Capacity (FVC)	The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters.	Baseline and Week 16	No
Secondary	Change in Forced Expiratory Flow Rate (FEF) 25-75%	FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.	Baseline and Week 4	No
Secondary	Change in Forced Expiratory Flow Rate (FEF) 25-75%	FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.	Baseline and Week 8	No
Secondary	Change in Forced Expiratory Flow Rate (FEF) 25-75%	FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.	Baseline and Week 12	No
Secondary	Change in Forced Expiratory Flow Rate (FEF) 25-75%	FEF 25-75% is the average forced expiratory flow rate during the middle portion of expiration.	Baseline and Week 16	No
Secondary	Change in Beta-agonist use	The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.	Baseline and Week 4	No
Secondary	Change in Beta-agonist use	The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.	Baseline and Week 8	No
Secondary	Change in Beta-agonist use	The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.	Baseline and Week 12	No
Secondary	Change in Beta-agonist use	The number of times a beta-agonist therapy is used will be assessed using 3-day recall at scheduled visits. Patients will be asked to recall date and time of any use of beta-agonist therapy, name of medicine, and number of puffs inhaled.	Baseline and Week 16	No
Secondary	Change in blood eosinophil count	The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.	Baseline and Week 4	No
Secondary	Change in blood eosinophil count	The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.	Baseline and Week 8	No
Secondary	Change in blood eosinophil count	The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.	Baseline and Week 12	No
Secondary	Change in blood eosinophil count	The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.	Baseline and Week 16	No
Secondary	Change in blood eosinophil count	The blood eosinophil counts will be measured using a standard complete blood count (CBC) with differential blood test. The results of the differential will be blinded.	Baseline and 12 weeks after end of treatment (EOT) or early withdrawal	No
Secondary	Change in Asthma Control Questionnaire (ACQ) Score	The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.	Baseline and Week 4	No
Secondary	Change in Asthma Control Questionnaire (ACQ) Score	The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.	Baseline and Week 8	No
Secondary	Change in Asthma Control Questionnaire (ACQ) Score	The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.	Baseline and Week 12	No
Secondary	Change in Asthma Control Questionnaire (ACQ) Score	The ACQ is a validated asthma assessment tool that has been widely used. Six questions are self assessments; the seventh item is the result of the patient's FEV1 measurement. Each item on the ACQ has a possible score ranging from 0 (indicating that the asthma is well controlled) to 6 (indicating that the asthma is severely uncontrolled), and the total score is the mean of all responses.	Baseline and Week 16	No
Secondary	Summary of participants with Adverse Events		16 weeks	Yes