Clinical trial NCT01270464: A Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma
Official title: A 16-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic 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: 2011-01-05
Enrollment: 315
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine whether reslizumab, at a dosage of 0.3 or 3.0 mg/kg administered once every 4 weeks for a total of 4 doses, is more effective than placebo in improving lung function in patients with eosinophilic asthma as assessed by the overall change from baseline in forced expiratory volume in 1 second (FEV1).


Eligibility criteria: Inclusion Criteria:

* The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma. Patients 12 through 17 years of age are excluded from participating in Argentina.
* The patient has an ACQ score of at least 1.5.
* The patient has airway reversibility of at least 12% to beta-agonist administration at screening.
* 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.
* The patient has a blood eosinophil count of at least 400/μL.
* Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ßHCG 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 the end-of-treatment visit. 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. Patients 12 through 17 years old, where participating, need to provide assent in accordance with local standards.
* Other inclusion criteria apply.

Exclusion Criteria:

* 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 has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis).
* 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-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor mAb) within 6 months prior to study entry (screening).
* The patient is currently using systemic corticosteroids (includes use of oral corticosteroids).
* The patient has a current infection or disease that may preclude assessment of asthma.
* 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 (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 anti-hIL-5 monoclonal antibody (eg, mepolizumab).
* Female patients who are pregnant, or nursing, or, if of childbearing potential and not using a medically accepted, effective method of birth control (e.g. spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this 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). Patients in Argentina must have documented serology testing for HIV performed during screening.
* Other exclusion criteria apply.

Primary outcomes:
measure: Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 0 (baseline, pre-dose), Weeks 4, 8, 12 and 16
Secondary outcomes:
measure: Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
measure: Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
measure: Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint
timeFrame: Day 1 (baseline, pre-dose), Week 16, endpoint
measure: Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
measure: Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value
timeFrame: Day 1 (baseline, pre-dose), Week 16 or last observed value
measure: Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
measure: Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
measure: Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
measure: Participants With Adverse Events
timeFrame: Day 1 (post-dose) to Week 29
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
timeFrame: Day 2 to Week 29
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
timeFrame: Day 2 to Week 29
measure: Shifts From Baseline to Endpoint in Electrocardiogram Findings
timeFrame: Weeks -4 to -2 (Screening Visit), Week 16
measure: Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall
timeFrame: Day 1 (pre-dose), week 8, 16 and endpoint
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Teva Investigational Site 12
state: California
city: Fountain Valley
country: United States
facility: Teva Investigational Site 11
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 43
state: California
city: Orange
country: United States
facility: Teva Investigational Site 4
state: California
city: Walnut Creek
country: United States
facility: Teva Investigational Site 15
state: California
city: Colorado Springs
country: United States
facility: Teva Investigational Site 2
state: Colorado
city: Largo
country: United States
facility: Teva Investigational Site 24
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 27
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 5
state: Florida
city: Tallahassee
country: United States
facility: Teva Investigational Site 19
state: Florida
city: Trinity
country: United States
facility: Teva Investigational Site 17
state: Florida
city: Valrico
country: United States
facility: Teva Investigational Site 18
state: Florida
city: Lilburn
country: United States
facility: Teva Investigational Site 6
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 3
state: Georgia
city: Iowa City
country: United States
facility: Teva Investigational Site 7
state: Iowa
city: Omaha
country: United States
facility: Teva Investigational Site 8
state: Nebraska
city: Summit
country: United States
facility: Teva Investigational Site 26
state: New Jersey
city: Cincinnati
country: United States
facility: Teva Investigational Site 20
state: Ohio
city: Medford
country: United States
facility: Teva Investigational Site 1
state: Oregon
city: Lincoln
country: United States
facility: Teva Investigational Site 73
state: Rhode Island
city: Providence
country: United States
facility: Teva Investigational Site 9
state: Rhode Island
city: Charleston
country: United States
facility: Teva Investigational Site 21
state: South Carolina
city: Fort Worth
country: United States
facility: Teva Investigational Site 16
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 10
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 14
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 45
state: Texas
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Teva Investigational Site 121
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Teva Investigational Site 126
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Teva Investigational Site 127
city: Quilmes-Buenos Aires
country: Argentina
facility: Teva Investigational Site 128
city: Rosario-Santa Fe
country: Argentina
facility: Teva Investigational Site 123
city: Rosario
country: Argentina
facility: Teva Investigational Site 125
city: San Miguel de Tucuman - Tucuma
country: Argentina
facility: Teva Investigational Site 120
city: San Miguel de Tucuman - Tucuma
country: Argentina
facility: Teva Investigational Site 122
city: San Miguel de Tucuman - Tucuma
country: Argentina
facility: Teva Investigational Site 124
city: Bruxelles
country: Belgium
facility: Teva Investigational Site 261
city: Bruxelles
country: Belgium
facility: Teva Investigational Site 264
city: Gent
country: Belgium
facility: Teva Investigational Site 260
city: Liège
country: Belgium
facility: Teva Investigational Site 263
city: Belo Horizonte
country: Brazil
facility: Teva Investigational Site 146
city: Florianopolis
country: Brazil
facility: Teva Investigational Site 150
city: Porto Alegre - RS
country: Brazil
facility: Teva Investigational Site 147
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 140
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 143
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 144
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 145
city: Santo André, São Paulo
country: Brazil
facility: Teva Investigational Site 142
city: Sao Paulo
country: Brazil
facility: Teva Investigational Site 141
city: Calgary
country: Canada
facility: Teva Investigational Site 103
city: Montreal
country: Canada
facility: Teva Investigational Site 101
city: Newmarket
country: Canada
facility: Teva Investigational Site 104
city: Windsor
country: Canada
facility: Teva Investigational Site 105
city: Bogota
country: Colombia
facility: Teva Investigational Site 184
city: Bogota
country: Colombia
facility: Teva Investigational Site 185
city: Bogotá
country: Colombia
facility: Teva Investigational Site 181
city: Cali
country: Colombia
facility: Teva Investigational Site 182
city: Floridablanca
country: Colombia
facility: Teva Investigational Site 180
city: Medellin
country: Colombia
facility: Teva Investigational Site 183
city: Grenoble
country: France
facility: Teva Investigational Site 343
city: Marseille
country: France
facility: Teva Investigational Site 342
city: Montpellier
country: France
facility: Teva Investigational Site 341
city: Nantes
country: France
facility: Teva Investigational Site 340
city: Pessac
country: France
facility: Teva Investigational Site 344
city: Balassagyarmat
country: Hungary
facility: Teva Investigational Site 401
city: Edelény
country: Hungary
facility: Teva Investigational Site 406
city: Miskolc
country: Hungary
facility: Teva Investigational Site 400
city: Mosonmagyaróvár
country: Hungary
facility: Teva Investigational Site 404
city: Sopron
country: Hungary
facility: Teva Investigational Site 403
city: Százhalombatta
country: Hungary
facility: Teva Investigational Site 407
city: Tatabánya
country: Hungary
facility: Teva Investigational Site 402
city: Petach Tikva
country: Israel
facility: Teva Investigational Site 422
city: Rehovot
country: Israel
facility: Teva Investigational Site 421
city: Tel-Aviv
country: Israel
facility: Teva Investigational Site 420
city: Distrito Federal
country: Mexico
facility: Teva Investigational Site 203
city: Distrito Federal
country: Mexico
facility: Teva Investigational Site 205
city: Guadalajara, JAL
country: Mexico
facility: Teva Investigational Site 204
city: Hermosillo, Sonora
country: Mexico
facility: Teva Investigational Site 200
city: Tijuana, B.C.
country: Mexico
facility: Teva Investigational Site 202
city: Heerlen
country: Netherlands
facility: Teva Investigational Site 460
city: Bialystok
country: Poland
facility: Teva Investigational Site 507
city: Gdansk
country: Poland
facility: Teva Investigational Site 513
city: Lodz
country: Poland
facility: Teva Investigational Site 512
city: Lublin
country: Poland
facility: Teva Investigational Site 505
city: Ostrow Wielkopolski
country: Poland
facility: Teva Investigational Site 500
city: Sopot
country: Poland
facility: Teva Investigational Site 502
city: Tarnow
country: Poland
facility: Teva Investigational Site 504
city: Göteborg
country: Sweden
facility: Teva Investigational Site 602
city: Lund
country: Sweden
facility: Teva Investigational Site 600
city: Malmö
country: Sweden
facility: Teva Investigational Site 601
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert, Senior Director - Worldwide Clinical Research, MD
role: STUDY_DIRECTOR
References:
citation: Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study. Chest. 2016 Oct;150(4):789-798. doi: 10.1016/j.chest.2016.03.032. Epub 2016 Apr 4.