Clinical trial NCT01287039: A Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma
Official title: A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in 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: 2011-02-01
Enrollment: 489
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: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in patients with eosinophilic asthma.

Detailed description: Demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered iv every 4 weeks over 12 months, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs) during 12 months.

An exacerbation event will be considered a CAE if the patient meets either or both of the criteria listed below and this is corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma:

* use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days
* asthma-related emergency treatment The above criteria must be corroborated with at least 1 other measurement to indicate worsening in the clinical signs and symptoms of asthma.

Eligibility criteria: Inclusion Criteria:

* The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma.
* The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening.
* The patient has a current blood eosinophil level of at least 400/μl.
* The patient has airway reversibility of at least 12% to beta-agonist administration.
* The patient has an ACQ score of at least 1.5 at the screening and baseline (before the 1st dose of study drug) visits.
* The patient is taking inhaled fluticasone at a dosage of at least 440 μg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, oral corticosteroids up to a maximum of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout study.
* All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ß-human chorionic gonadotropin \[ß-HCG\]) 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.
* Written informed consent is obtained. Patients 12 through 17 years old must provide assent.
* 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, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis.

  * Other criteria apply; please contact the investigator for more information.

Exclusion Criteria:

* The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
* The patient has known hypereosinophilic syndrome.
* The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded.
* The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
* The patient is using systemic immunosuppressive or immunomodulating or other biologic agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor \[anti TNF\] mAb) within 6 months prior to screening.
* The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab).
* The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).
* 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 6 months prior to screening.
* Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control.

  * Other criteria apply; please contact the investigator for more information.

Primary outcomes:
measure: Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment
timeFrame: Day 1 to Week 52
measure: Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)
timeFrame: Day 1 to Week 52
Secondary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16
measure: Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16
timeFrame: Day 1 (baseline, pre-dose), Week 16
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: Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)
timeFrame: Day 1 to Day 478 (longest treatment time plus 2 weeks)
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 and 52 Weeks Using Mixed Model for Repeated Measures
timeFrame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal
measure: Participants With Treatment-Emergent Adverse Events
timeFrame: Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
timeFrame: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
timeFrame: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each
measure: Participants With a Positive Anti-Reslizumab Antibody Status During Study
timeFrame: Weeks 16, 32, 48 and 52
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Teva Investigational Site 58
state: Arizona
city: Los Angeles
country: United States
facility: Teva Investigational Site 61
state: California
city: Orange
country: United States
facility: Teva Investigational Site 37
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 56
state: California
city: Colorado Springs
country: United States
facility: Teva Investigational Site 34
state: Colorado
city: DeBary
country: United States
facility: Teva Investigational Site 52
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 55
state: Florida
city: Valrico
country: United States
facility: Teva Investigational Site 18
state: Florida
city: Lexington
country: United States
facility: Teva Investigational Site 49
state: Kentucky
city: Louisville
country: United States
facility: Teva Investigational Site 65
state: Kentucky
city: Boston
country: United States
facility: Teva Investigational Site 51
state: Massachusetts
city: Saint Louis
country: United States
facility: Teva Investigational Site 74
state: Missouri
city: Missoula
country: United States
facility: Teva Investigational Site 35
state: Montana
city: Boys Town
country: United States
facility: Teva Investigational Site 64
state: Nebraska
city: Bronx
country: United States
facility: Teva Investigational Site 60
state: New York
city: Rochester
country: United States
facility: Teva Investigational Site 68
state: New York
city: Winston-Salem
country: United States
facility: Teva Investigational Site 30
state: North Carolina
city: Cincinnati
country: United States
facility: Teva Investigational Site 31
state: Ohio
city: Columbus
country: United States
facility: Teva Investigational Site 62
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 50
state: Oklahoma
city: Altoona
country: United States
facility: Teva Investigational Site 66
state: Pennsylvania
city: Nashville
country: United States
facility: Teva Investigational Site 32
state: Tennessee
city: Boerne
country: United States
facility: Teva Investigational Site 63
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 72
state: Texas
city: Richmond
country: United States
facility: Teva Investigational Site 38
state: Virginia
city: Madison
country: United States
facility: Teva Investigational Site 33
state: Wisconsin
city: Nedlands
country: Australia
facility: Teva Investigational Site 643
state: Western Australia
city: Clayton
country: Australia
facility: Teva Investigational Site 641
city: Daw Park
country: Australia
facility: Teva Investigational Site 644
city: Frankston
country: Australia
facility: Teva Investigational Site 642
city: Liverpool
country: Australia
facility: Teva Investigational Site 645
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: Jambes
country: Belgium
facility: Teva Investigational Site 262
city: Liège
country: Belgium
facility: Teva Investigational Site 263
city: Rancagua
country: Chile
facility: Teva Investigational Site 160
city: Santiago
country: Chile
facility: Teva Investigational Site 163
city: Santiago
country: Chile
facility: Teva Investigational Site 164
city: Santiago
country: Chile
facility: Teva Investigational Site 165
city: Temuco
country: Chile
facility: Teva Investigational Site 161
city: Valdivia
country: Chile
facility: Teva Investigational Site 162
city: Valparaiso
country: Chile
facility: Teva Investigational Site 166
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: Breclav
country: Czechia
facility: Teva Investigational Site 284
city: Brno
country: Czechia
facility: Teva Investigational Site 287
city: Liberec
country: Czechia
facility: Teva Investigational Site 286
city: Olomouc
country: Czechia
facility: Teva Investigational Site 280
city: Olomouc
country: Czechia
facility: Teva Investigational Site 281
city: Olomouc
country: Czechia
facility: Teva Investigational Site 285
city: Tabor
country: Czechia
facility: Teva Investigational Site 283
city: Hvidovre
country: Denmark
facility: Teva Investigational Site 301
city: Odense
country: Denmark
facility: Teva Investigational Site 300
city: Balassagyarmat
country: Hungary
facility: Teva Investigational Site 401
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: Törökbálint
country: Hungary
facility: Teva Investigational Site 405
city: Ashkelon
country: Israel
facility: Teva Investigational Site 423
city: Beer-Sheva
country: Israel
facility: Teva Investigational Site 430
city: Haifa
country: Israel
facility: Teva Investigational Site 431
city: Haifa
country: Israel
facility: Teva Investigational Site 432
city: Jerusalem
country: Israel
facility: Teva Investigational Site 425
city: Jerusalem
country: Israel
facility: Teva Investigational Site 428
city: Jerusalem
country: Israel
facility: Teva Investigational Site 429
city: Kfar Saba
country: Israel
facility: Teva Investigational Site 426
city: Petach Tikva
country: Israel
facility: Teva Investigational Site 422
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 427
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 433
city: Rehovot
country: Israel
facility: Teva Investigational Site 421
city: Tel-Aviv
country: Israel
facility: Teva Investigational Site 420
city: Batu Caves
country: Malaysia
facility: Teva Investigational Site 705
city: Kuala Lumpur
country: Malaysia
facility: Teva Investigational Site 700
city: Kuala Lumpur
country: Malaysia
facility: Teva Investigational Site 702
city: Kuantan
country: Malaysia
facility: Teva Investigational Site 703
city: Penang
country: Malaysia
facility: Teva Investigational Site 701
city: Taiping
country: Malaysia
facility: Teva Investigational Site 704
city: Auckland
country: New Zealand
facility: Teva Investigational Site 723
city: Christchurch
country: New Zealand
facility: Teva Investigational Site 722
city: Christchurch
country: New Zealand
facility: Teva Investigational Site 726
city: Dunedin
country: New Zealand
facility: Teva Investigational Site 724
city: Hamilton
country: New Zealand
facility: Teva Investigational Site 727
city: Tauranga
country: New Zealand
facility: Teva Investigational Site 720
city: Wellington
country: New Zealand
facility: Teva Investigational Site 721
city: Governor Mangubat Drive, Dasma
country: Philippines
facility: Teva Investigational Site 744
city: Manila
country: Philippines
facility: Teva Investigational Site 742
city: Quezon City
country: Philippines
facility: Teva Investigational Site 740
city: Quezon City
country: Philippines
facility: Teva Investigational Site 741
city: Quezon City
country: Philippines
facility: Teva Investigational Site 743
city: Quezon City
country: Philippines
facility: Teva Investigational Site 745
city: Bialystok
country: Poland
facility: Teva Investigational Site 507
city: Bydgoszcz
country: Poland
facility: Teva Investigational Site 509
city: Bystra
country: Poland
facility: Teva Investigational Site 501
city: Ostrow Wielkopolski
country: Poland
facility: Teva Investigational Site 500
city: Poznan
country: Poland
facility: Teva Investigational Site 511
city: Sopot
country: Poland
facility: Teva Investigational Site 502
city: Tarnow
country: Poland
facility: Teva Investigational Site 504
city: Barnaul
country: Russian Federation
facility: Teva Investigational Site 545
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 551
city: Kemerovo
country: Russian Federation
facility: Teva Investigational Site 549
city: Nizhniy Novgorod
country: Russian Federation
facility: Teva Investigational Site 550
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 553
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 555
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 542
city: Tomsk
country: Russian Federation
facility: Teva Investigational Site 552
city: Yaroslavl
country: Russian Federation
facility: Teva Investigational Site 546
city: Cape Town
country: South Africa
facility: Teva Investigational Site 581
city: Cape Town
country: South Africa
facility: Teva Investigational Site 584
city: Cape Town
country: South Africa
facility: Teva Investigational Site 586
city: Centurion
country: South Africa
facility: Teva Investigational Site 587
city: Durban
country: South Africa
facility: Teva Investigational Site 582
city: Durban
country: South Africa
facility: Teva Investigational Site 585
city: Johannesburg
country: South Africa
facility: Teva Investigational Site 580
city: Johannesburg
country: South Africa
facility: Teva Investigational Site 589
city: Pretoria
country: South Africa
facility: Teva Investigational Site 583
city: Pretoria
country: South Africa
facility: Teva Investigational Site 588
city: Göteborg
country: Sweden
facility: Teva Investigational Site 602
city: Göteborg
country: Sweden
facility: Teva Investigational Site 604
city: Linköping
country: Sweden
facility: Teva Investigational Site 603
city: Malmö
country: Sweden
facility: Teva Investigational Site 601
city: Bangkok
country: Thailand
facility: Teva Investigational Site 780
city: Bangkok
country: Thailand
facility: Teva Investigational Site 782
city: Bangkok
country: Thailand
facility: Teva Investigational Site 783
city: Muang
country: Thailand
facility: Teva Investigational Site 781
city: Nakhon Ratchasima
country: Thailand
facility: Teva Investigational Site 784
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Nair P, Bardin P, Humbert M, Murphy KR, Hickey L, Garin M, Vanlandingham R, Chanez P. Efficacy of Intravenous Reslizumab in Oral Corticosteroid-Dependent Asthma. J Allergy Clin Immunol Pract. 2020 Feb;8(2):555-564. doi: 10.1016/j.jaip.2019.09.036. Epub 2019 Oct 15.
citation: Carr WW, McDonald M, Meizlik P. Effect of intravenously administered reslizumab on spirometric lung age in patients with moderate-to-severe eosinophilic asthma. Allergy Asthma Proc. 2019 Jul 1;40(4):240-249. doi: 10.2500/aap.2019.40.4225.
citation: Han S, Kim S, Kim H, Suh HS. Cost-utility analysis of reslizumab for patients with severe eosinophilic asthma inadequately controlled with high-dose inhaled corticosteroids and long-acting beta2-agonists in South Korea. Curr Med Res Opin. 2019 Sep;35(9):1597-1605. doi: 10.1080/03007995.2019.1605159. Epub 2019 May 16.
citation: Bateman ED, Djukanovic R, Castro M, Canvin J, Germinaro M, Noble R, Garin M, Buhl R. Predicting Responders to Reslizumab after 16 Weeks of Treatment Using an Algorithm Derived from Clinical Studies of Patients with Severe Eosinophilic Asthma. Am J Respir Crit Care Med. 2019 Feb 15;199(4):489-495. doi: 10.1164/rccm.201708-1668OC.
citation: Weinstein SF, Katial RK, Bardin P, Korn S, McDonald M, Garin M, Bateman ED, Hoyte FCL, Germinaro M. Effects of Reslizumab on Asthma Outcomes in a Subgroup of Eosinophilic Asthma Patients with Self-Reported Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2019 Feb;7(2):589-596.e3. doi: 10.1016/j.jaip.2018.08.021. Epub 2018 Sep 5.
citation: Brusselle G, Germinaro M, Weiss S, Zangrilli J. Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils. Pulm Pharmacol Ther. 2017 Apr;43:39-45. doi: 10.1016/j.pupt.2017.01.011. Epub 2017 Jan 31.
citation: Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O'Brien C, Korn S. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015 May;3(5):355-66. doi: 10.1016/S2213-2600(15)00042-9. Epub 2015 Feb 23.