Clinical trial NCT01508936: Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Asthma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-12
Enrollment: 511
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in Full Analysis Set
timeFrame: Baseline (Day 1), Week 16
Secondary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, 16
measure: Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, 16
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in FEV1 Subpopulation
timeFrame: Baseline (Day 1), Week 16
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, and 16
measure: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, and 16
measure: Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, and 16
measure: 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
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, and 16
measure: Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16
timeFrame: Baseline (Day -2 to 1), Weeks 4, 8, 12, and 16
measure: Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint
timeFrame: Baseline (Day 1), Weeks 4, 8, 12, 16, Follow-up (Week 28)
measure: Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16
timeFrame: Baseline (Day 1), Weeks 4, 8, 12 and 16
measure: Participants With Treatment-Emergent Adverse Events
timeFrame: Day 1 to Week 28
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
timeFrame: Week 4 to Week 16
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
timeFrame: Week 4 to Week 28
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Electrocardiogram (ECG) Abnormalities
timeFrame: Week 16 or endpoint
measure: Participants With a Positive Anti-Reslizumab Antibody Status During Study
timeFrame: Screening (Week -3), Weeks 8 and 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site 861
state: Alabama
city: Homewood
country: United States
facility: Investigational Site 842
state: Alabama
city: Jasper
country: United States
facility: Investigational Site 887
state: Alabama
city: Tucson
country: United States
facility: Investigational Site 809
state: Arizona
city: Tucson
country: United States
facility: Investigational Site 892
state: Arizona
city: Little Rock
country: United States
facility: Investigational Site 846
state: Arkansas
city: Anaheim
country: United States
facility: Investigational Site 828
state: California
city: Fresno
country: United States
facility: Investigational Site 900
state: California
city: Huntington Beach
country: United States
facility: Investigational Site 862
state: California
city: Los Angeles
country: United States
facility: Investigational Site 852
state: California
city: Los Angeles
country: United States
facility: Investigational Site 909
state: California
city: Newport Beach
country: United States
facility: Investigational Site 864
state: California
city: Rancho Mirage
country: United States
facility: Investigational Site 812
state: California
city: Riverside
country: United States
facility: Investigational Site 808
state: California
city: Sacramento
country: United States
facility: Investigational Site 804
state: California
city: Centennial
country: United States
facility: Investigational Site 837
state: Colorado
city: Denver
country: United States
facility: Investigational Site 851
state: Colorado
city: Wheat Ridge
country: United States
facility: Investigational Site 832
state: Colorado
city: Jacksonville
country: United States
facility: Investigational Site 855
state: Florida
city: Miami
country: United States
facility: Investigational Site 865
state: Florida
city: Miami
country: United States
facility: Investigational Site 881
state: Florida
city: Albany
country: United States
facility: Investigational Site 805
state: Georgia
city: Stockbridge
country: United States
facility: Investigational Site 870
state: Georgia
city: Chicago
country: United States
facility: Investigational Site 816
state: Illinois
city: Shiloh
country: United States
facility: Investigational Site 824
state: Illinois
city: Evansville
country: United States
facility: Investigational Site 883
state: Indiana
city: Fort Wayne
country: United States
facility: Investigational Site 878
state: Indiana
city: Lenexa
country: United States
facility: Investigational Site 820
state: Kansas
city: Owensboro
country: United States
facility: Investigational Site 873
state: Kentucky
city: Lafayette
country: United States
facility: Investigational Site 801
state: Louisiana
city: Mandeville
country: United States
facility: Investigational Site 877
state: Louisiana
city: White Marsh
country: United States
facility: Investigational Site 875
state: Maryland
city: Fall River
country: United States
facility: Investigational Site 871
state: Massachusetts
city: North Dartmouth
country: United States
facility: Investigational Site 834
state: Massachusetts
city: Troy
country: United States
facility: Investigational Site 889
state: Michigan
city: Rolla
country: United States
facility: Investigational Site 838
state: Missouri
city: St. Louis
country: United States
facility: Investigational Site 818
state: Missouri
city: St. Louis
country: United States
facility: Investigational Site 841
state: Missouri
city: Albuquerque
country: United States
facility: Investigational Site 857
state: New Mexico
city: Newburgh
country: United States
facility: Investigational Site 819
state: New York
city: Charlotte
country: United States
facility: Investigational Site 844
state: North Carolina
city: Middleburg Heights
country: United States
facility: Investigational Site 845
state: Ohio
city: Tulsa
country: United States
facility: Investigational Site 810
state: Oklahoma
city: Ashland
country: United States
facility: Investigational Site 859
state: Oregon
city: Portland
country: United States
facility: Investigational Site 859
state: Oregon
city: Jenkintown
country: United States
facility: Investigational Site 854
state: Pennsylvania
city: Providence
country: United States
facility: Investigational Site 843
state: Rhode Island
city: Florence
country: United States
facility: Investigational Site 802
state: South Carolina
city: Orangeburg
country: United States
facility: Investigational Site 814
state: South Carolina
city: Spartanburg
country: United States
facility: Investigational Site 821
state: South Carolina
city: Spartanburg
country: United States
facility: Investigational Site 829
state: South Carolina
city: Knoxville
country: United States
facility: Investigational Site 850
state: Tennessee
city: Nashville
country: United States
facility: Investigational Site 803
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site 880
state: Texas
city: Dickinson
country: United States
facility: Investigational Site 858
state: Texas
city: Live Oak
country: United States
facility: Investigational Site 869
state: Texas
city: Plano
country: United States
facility: Investigational Site 879
state: Texas
city: Salt Lake City
country: United States
facility: Investigational Site 847
state: Utah
city: West Jordan
country: United States
facility: Investigational Site 876
state: Utah
city: Fairfax
country: United States
facility: Investigational Site 840
state: Virginia
city: Richmond
country: United States
facility: Investigational Site 836
state: Virginia
city: Seattle
country: United States
facility: Investigational Site 867
state: Washington
city: Spokane
country: United States
facility: Investigational Site 833
state: Washington
city: Vancouver
country: United States
facility: Investigational Site 904
state: Washington
city: Greenfield
country: United States
facility: Investigational Site 806
state: Wisconsin
city: LaCrosse
country: United States
facility: Investigational Site 823
state: Wisconsin
Study officials:
affiliation: Sponsor's Medical Expert
name: Global Respiratory Clinical Research, M.D.
role: STUDY_DIRECTOR
References:
citation: Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts. Chest. 2016 Oct;150(4):799-810. doi: 10.1016/j.chest.2016.03.018. Epub 2016 Mar 25.