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

NCT01287039 | Completed Phase 3 Results

• 1 other identifier: C38072/3082
• Study Type: interventional
• Target: 489
• Locations: 17 countries
• Sites: 128

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.

Conditions

Eosinophilic Asthma

Outcome Measures

Primary Outcomes (2)

• Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment

  An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was 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; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.

  Day 1 to Week 52

• Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)

  An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was 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; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals for the two criteria were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.

  Day 1 to Week 52

Secondary Outcomes (11)

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures

  Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16

• Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16

  Day 1 (baseline, pre-dose), Week 16

• Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures

  Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

• Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)

  Day 1 to Day 478 (longest treatment time plus 2 weeks)

• Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures

  Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.

Drug: Placebo

Reslizumab 3.0 mg/kg

EXPERIMENTAL

Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.

Drug: Reslizumab

Interventions

Reslizumab DRUG

Patients were administered intravenously over 15 to 30 minutes reslizumab at a dosage of 3.0 mg/kg at baseline and once every 4 weeks relative to baseline over 48 weeks for a total of 13 doses.

Also known as: Cinquil, humanized monoclonal antibody, CEP-38072

Reslizumab 3.0 mg/kg

Placebo DRUG

Matching placebo (20 mM sodium acetate, 7% sucrose), administered intravenously (iv) once every 4 weeks over 52 weeks, for a total of 13 doses administered. Each patient received a specific volume of placebo to match the volume of reslizumab on the basis of the patient's body weight.

Placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (128)

Teva Investigational Site 58

Scottsdale, Arizona, United States

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Teva Investigational Site 61

Los Angeles, California, United States

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Teva Investigational Site 37

Orange, California, United States

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Teva Investigational Site 56

San Diego, California, United States

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Teva Investigational Site 34

Colorado Springs, Colorado, United States

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Teva Investigational Site 52

DeBary, Florida, United States

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Teva Investigational Site 55

Miami, Florida, United States

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Teva Investigational Site 18

Valrico, Florida, United States

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Teva Investigational Site 49

Lexington, Kentucky, United States

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Teva Investigational Site 65

Louisville, Kentucky, United States

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Teva Investigational Site 51

Boston, Massachusetts, United States

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Teva Investigational Site 74

St Louis, Missouri, United States

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Teva Investigational Site 35

Missoula, Montana, United States

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Teva Investigational Site 64

Boys Town, Nebraska, United States

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Teva Investigational Site 68

Rochester, New York, United States

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Teva Investigational Site 60

The Bronx, New York, United States

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Teva Investigational Site 30

Winston-Salem, North Carolina, United States

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Teva Investigational Site 31

Cincinnati, Ohio, United States

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Teva Investigational Site 62

Columbus, Ohio, United States

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Teva Investigational Site 50

Oklahoma City, Oklahoma, United States

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Teva Investigational Site 66

Altoona, Pennsylvania, United States

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Teva Investigational Site 32

Nashville, Tennessee, United States

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Teva Investigational Site 63

Boerne, Texas, United States

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Teva Investigational Site 72

Houston, Texas, United States

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Teva Investigational Site 38

Richmond, Virginia, United States

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Teva Investigational Site 33

Madison, Wisconsin, United States

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Teva Investigational Site 643

Nedlands, Western Australia, Australia

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Teva Investigational Site 641

Clayton, Australia

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Teva Investigational Site 644

Daw Park, Australia

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Teva Investigational Site 642

Frankston, Australia

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Teva Investigational Site 645

Liverpool, Australia

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Teva Investigational Site 261

Brussels, Belgium

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Teva Investigational Site 264

Brussels, Belgium

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Teva Investigational Site 260

Ghent, Belgium

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Teva Investigational Site 262

Jambes, Belgium

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Teva Investigational Site 263

Liège, Belgium

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Teva Investigational Site 160

Rancagua, Chile

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Teva Investigational Site 163

Santiago, Chile

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Teva Investigational Site 164

Santiago, Chile

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Teva Investigational Site 165

Santiago, Chile

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Teva Investigational Site 161

Temuco, Chile

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Teva Investigational Site 162

Valdivia, Chile

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Teva Investigational Site 166

Valparaíso, Chile

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Teva Investigational Site 181

Bogotá, Colombia

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Teva Investigational Site 185

Bogotá, Colombia

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Teva Investigational Site 182

Cali, Colombia

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Teva Investigational Site 180

Floridablanca, Colombia

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Teva Investigational Site 287

Brno, Czechia

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Teva Investigational Site 284

Břeclav, Czechia

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Teva Investigational Site 286

Liberec, Czechia

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Teva Investigational Site 280

Olomouc, Czechia

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Teva Investigational Site 281

Olomouc, Czechia

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Teva Investigational Site 285

Olomouc, Czechia

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Teva Investigational Site 283

Tábor, Czechia

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Teva Investigational Site 301

Hvidovre, Denmark

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Teva Investigational Site 300

Odense, Denmark

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Teva Investigational Site 401

Balassagyarmat, Hungary

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Teva Investigational Site 400

Miskolc, Hungary

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Teva Investigational Site 404

Mosonmagyaróvár, Hungary

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Teva Investigational Site 403

Sopron, Hungary

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Teva Investigational Site 405

Törökbálint, Hungary

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Teva Investigational Site 423

Ashkelon, Israel

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Teva Investigational Site 430

Beersheba, Israel

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Teva Investigational Site 431

Haifa, Israel

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Teva Investigational Site 432

Haifa, Israel

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Teva Investigational Site 425

Jerusalem, Israel

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Teva Investigational Site 428

Jerusalem, Israel

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Teva Investigational Site 429

Jerusalem, Israel

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Teva Investigational Site 426

Kfar Saba, Israel

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Teva Investigational Site 422

Petah Tikva, Israel

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Teva Investigational Site 427

Ramat Gan, Israel

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Teva Investigational Site 433

Ramat Gan, Israel

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Teva Investigational Site 421

Rehovot, Israel

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Teva Investigational Site 420

Tel Aviv, Israel

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Teva Investigational Site 705

Batu Caves, Malaysia

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Teva Investigational Site 701

George Town, Malaysia

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Teva Investigational Site 700

Kuala Lumpur, Malaysia

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Teva Investigational Site 702

Kuala Lumpur, Malaysia

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Teva Investigational Site 703

Kuantan, Malaysia

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Teva Investigational Site 704

Taiping, Malaysia

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Teva Investigational Site 723

Auckland, New Zealand

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Teva Investigational Site 722

Christchurch, New Zealand

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Teva Investigational Site 726

Christchurch, New Zealand

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Teva Investigational Site 724

Dunedin, New Zealand

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Teva Investigational Site 727

Hamilton, New Zealand

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Teva Investigational Site 720

Tauranga, New Zealand

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Teva Investigational Site 721

Wellington, New Zealand

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Teva Investigational Site 744

Governor Mangubat Drive, Dasma, Philippines

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Teva Investigational Site 742

Manila, Philippines

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Teva Investigational Site 740

Quezon City, Philippines

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Teva Investigational Site 741

Quezon City, Philippines

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Teva Investigational Site 743

Quezon City, Philippines

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Teva Investigational Site 745

Quezon City, Philippines

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Teva Investigational Site 507

Bialystok, Poland

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Teva Investigational Site 509

Bydgoszcz, Poland

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Teva Investigational Site 501

Bystra, Poland

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Teva Investigational Site 500

Ostrów Wielkopolski, Poland

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Teva Investigational Site 511

Poznan, Poland

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Teva Investigational Site 502

Sopot, Poland

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Teva Investigational Site 504

Tarnów, Poland

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Teva Investigational Site 545

Barnaul, Russia

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Teva Investigational Site 551

Kazan', Russia

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Teva Investigational Site 549

Kemerovo, Russia

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Teva Investigational Site 550

Nizhny Novgorod, Russia

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Teva Investigational Site 553

Novosibirsk, Russia

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Teva Investigational Site 555

Novosibirsk, Russia

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Teva Investigational Site 542

Saint Petersburg, Russia

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Teva Investigational Site 552

Tomsk, Russia

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Teva Investigational Site 546

Yaroslavl, Russia

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Teva Investigational Site 581

Cape Town, South Africa

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Teva Investigational Site 584

Cape Town, South Africa

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Teva Investigational Site 586

Cape Town, South Africa

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Teva Investigational Site 587

Centurion, South Africa

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Teva Investigational Site 582

Durban, South Africa

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Teva Investigational Site 585

Durban, South Africa

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Teva Investigational Site 580

Johannesburg, South Africa

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Teva Investigational Site 589

Johannesburg, South Africa

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Teva Investigational Site 583

Pretoria, South Africa

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Teva Investigational Site 588

Pretoria, South Africa

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Teva Investigational Site 602

Gothenburg, Sweden

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Teva Investigational Site 604

Gothenburg, Sweden

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Teva Investigational Site 603

Linköping, Sweden

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Teva Investigational Site 601

Malmo, Sweden

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Teva Investigational Site 780

Bangkok, Thailand

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Teva Investigational Site 782

Bangkok, Thailand

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Teva Investigational Site 783

Bangkok, Thailand

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Teva Investigational Site 781

Muang, Thailand

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Teva Investigational Site 784

Nakhon Ratchasima, Thailand

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Related Publications (7)

• 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.

  PMID: 31626990 DERIVED

• 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.

  PMID: 31262379 DERIVED

• 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.

  PMID: 30964365 DERIVED

• 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.

  PMID: 30346831 DERIVED

• 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.

  PMID: 30193936 DERIVED

• 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.

  PMID: 28159511 DERIVED

• 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.

  PMID: 25736990 DERIVED

MeSH Terms

Conditions

Pulmonary Eosinophilia

Interventions

reslizumab; Antibodies, Monoclonal, Humanized

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2011
• First Posted: February 1, 2011
• Study Start: April 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: November 9, 2021
• Results First Posted: June 27, 2016

Record last verified: 2021-11

Locations

DK (2); US (26); PH (6); NZ (7); HU (5); CL (7); TH (5); CO (4); AU (5); MY (6); PL (7); RU (9); CZ (7); ZA (10); IL (13); BE (5); SE (4)