Clinical trial NCT01285323: A Study to Evaluate the Efficacy and Safety of Reslizumab in Patients 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: 2011-01-28
Enrollment: 464
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 is more effective than placebo in reducing the number of clinical asthma exacerbations (CAEs) in patients with eosinophilic asthma.


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 Germany, India, Argentina, and Korea; patients 66 through 75 years of age are excluded from participating in India and Korea.
* 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 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 dose of 10 mg prednisone daily or equivalent, leukotriene antagonists, 5-lipoxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline and must continue without dosage changes throughout the 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. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected). NOTE: Partner sterility alone is not acceptable for inclusion in the study.
* Written informed consent is obtained. Patients 12 through 17 years old, where participating, 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.
* The patient must be willing and able to understand and comply with study restrictions, requirements, and procedures, as specified by the study center, and to remain at the study center for the required duration during the study period, and willing to return to the study center for the follow-up evaluation as specified in this protocol.
* Patients who experience an asthma exacerbation during the screening period will be considered to have failed screening and cannot be randomly assigned to study drug. Patients may be rescreened 1 time only.

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, immunomodulating, or other biologic agents (including, but not limited to, anti-immunoglobulin E (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.
* Other exclusion criteria apply.

Primary outcomes:
measure: Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment
timeFrame: Day 1 to Month 12
measure: Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)
timeFrame: Day 1 to Month 12
Secondary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) At Week 16
timeFrame: Day 1 (baseline, pre-dose), Week 16
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 526 (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 TEAE)
timeFrame: Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
timeFrame: Week 4 to Week 52
measure: Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
timeFrame: Week 4 to Week 52
measure: Participants With a Positive Anti-Reslizumab Antibody Status During Study
timeFrame: Baseline visit (prior to reslizumab exposure), Weeks 16, 32, 48 and 52
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Teva Investigational Site 48
state: Alabama
city: Fresno
country: United States
facility: Teva Investigational Site 41
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 59
state: California
city: Denver
country: United States
facility: Teva Investigational Site 47
state: Colorado
city: Waterbury
country: United States
facility: Teva Investigational Site 28
state: Connecticut
city: Clearwater
country: United States
facility: Teva Investigational Site 53
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 27
state: Florida
city: Lawrenceville
country: United States
facility: Teva Investigational Site 25
state: Georgia
city: Metairie
country: United States
facility: Teva Investigational Site 57
state: Louisiana
city: Bangor
country: United States
facility: Teva Investigational Site 46
state: Maine
city: Saint Louis
country: United States
facility: Teva Investigational Site 40
state: Missouri
city: Fort Mill
country: United States
facility: Teva Investigational Site 67
state: South Carolina
city: Dallas
country: United States
facility: Teva Investigational Site 44
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 69
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: Rosario-Santa Fe
country: Argentina
facility: Teva Investigational Site 123
city: San Miguel De Tucuman - Tucuma
country: Argentina
facility: Teva Investigational Site 120
city: Florianopolis
country: Brazil
facility: Teva Investigational Site 150
city: Porto Alegre, RS
country: Brazil
facility: Teva Investigational Site 143
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 140
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: Newmarket
country: Canada
facility: Teva Investigational Site 104
city: Pointe-Claire
country: Canada
facility: Teva Investigational Site 102
city: Windsor
country: Canada
facility: Teva Investigational Site 105
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: Bad Wörishofen
country: Germany
facility: Teva Investigational Site 360
city: Berlin
country: Germany
facility: Teva Investigational Site 361
city: Berlin
country: Germany
facility: Teva Investigational Site 362
city: Berlin
country: Germany
facility: Teva Investigational Site 366
city: Bochum
country: Germany
facility: Teva Investigational Site 371
city: Dresden
country: Germany
facility: Teva Investigational Site 365
city: Frankfurt
country: Germany
facility: Teva Investigational Site 369
city: Hamburg
country: Germany
facility: Teva Investigational Site 370
city: Koblenz
country: Germany
facility: Teva Investigational Site 372
city: Leipzig
country: Germany
facility: Teva Investigational Site 367
city: Leipzig
country: Germany
facility: Teva Investigational Site 368
city: Mainz
country: Germany
facility: Teva Investigational Site 363
city: Mainz
country: Germany
facility: Teva Investigational Site 364
city: Alexandroupolis
country: Greece
facility: Teva Investigational Site 381
city: Athens
country: Greece
facility: Teva Investigational Site 380
city: Heraklion, Crete
country: Greece
facility: Teva Investigational Site 382
city: Gwangju
country: Korea, Republic of
facility: Teva Investigational Site 682
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 680
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 681
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 683
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 686
city: Suwon
country: Korea, Republic of
facility: Teva Investigational Site 685
city: Ciudad De México
country: Mexico
facility: Teva Investigational Site 205
city: Distrito Federal
country: Mexico
facility: Teva Investigational Site 203
city: Guadalajara, JAL
country: Mexico
facility: Teva Investigational Site 204
city: Mexico City
country: Mexico
facility: Teva Investigational Site 207
city: Monterrey
country: Mexico
facility: Teva Investigational Site 209
city: Tijuana, B.C.
country: Mexico
facility: Teva Investigational Site 202
city: Cercado De Lima, Lima
country: Peru
facility: Teva Investigational Site 223
city: Lima
country: Peru
facility: Teva Investigational Site 220
city: Lima
country: Peru
facility: Teva Investigational Site 221
city: Lima
country: Peru
facility: Teva Investigational Site 222
city: Lima
country: Peru
facility: Teva Investigational Site 225
city: Lima
country: Peru
facility: Teva Investigational Site 226
city: Lima
country: Peru
facility: Teva Investigational Site 227
city: Lima
country: Peru
facility: Teva Investigational Site 229
city: Bucharest
country: Romania
facility: Teva Investigational Site 523
city: Bucharest
country: Romania
facility: Teva Investigational Site 524
city: Cluj-Napoca
country: Romania
facility: Teva Investigational Site 520
city: Iasi
country: Romania
facility: Teva Investigational Site 521
city: Targu Mures
country: Romania
facility: Teva Investigational Site 522
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 543
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 544
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 554
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 556
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 558
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 559
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 557
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 541
city: St.Petersburg
country: Russian Federation
facility: Teva Investigational Site 540
city: Bradejov
country: Slovakia
facility: Teva Investigational Site 563
city: Levice
country: Slovakia
facility: Teva Investigational Site 561
city: Spisska Nova Ves
country: Slovakia
facility: Teva Investigational Site 560
city: Topolcany
country: Slovakia
facility: Teva Investigational Site 562
city: Kaohsiung
country: Taiwan
facility: Teva Investigational Site 764
city: Taichung
country: Taiwan
facility: Teva Investigational Site 765
city: Taipei
country: Taiwan
facility: Teva Investigational Site 760
city: Taipei
country: Taiwan
facility: Teva Investigational Site 761
city: Taoyuan
country: Taiwan
facility: Teva Investigational Site 763
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 621
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 629
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 635
city: Ivano-Frankivsk
country: Ukraine
facility: Teva Investigational Site 630
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 620
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 633
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 622
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 623
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 624
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 625
city: Ternopil
country: Ukraine
facility: Teva Investigational Site 628
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 626
city: Zaporizhzhia
country: Ukraine
facility: Teva Investigational Site 631
city: Zaporizhzhia
country: Ukraine
facility: Teva Investigational Site 632
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.