A Study to Evaluate the Efficacy and Safety of Reslizumab in Patients With Eosinophilic Asthma

NCT01285323 | Completed Phase 3 Results DMC

• 2 other identifiers: C38072/30832010-024006-35
• Study Type: interventional
• Target: 464
• Locations: 15 countries
• Sites: 104

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.

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 Month 12

• 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 Month 12

Secondary Outcomes (12)

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) At Week 16

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

• 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 526 (longest treatment time plus 2 weeks)

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 (acetate sucrose buffer), administered intravenously (iv) once every 4 weeks for a total of 13 doses.

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. 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).
• 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.

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, 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.

Sponsors & Collaborators

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

Study Sites (104)

Teva Investigational Site 48

Mobile, Alabama, United States

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Teva Investigational Site 41

Fresno, California, United States

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Teva Investigational Site 59

Long Beach, California, United States

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Teva Investigational Site 47

Denver, Colorado, United States

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Teva Investigational Site 28

Waterbury, Connecticut, United States

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Teva Investigational Site 53

Clearwater, Florida, United States

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Teva Investigational Site 27

Miami, Florida, United States

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Teva Investigational Site 25

Lawrenceville, Georgia, United States

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Teva Investigational Site 57

Metairie, Louisiana, United States

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Teva Investigational Site 46

Bangor, Maine, United States

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Teva Investigational Site 40

St Louis, Missouri, United States

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Teva Investigational Site 67

Fort Mill, South Carolina, United States

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Teva Investigational Site 44

Dallas, Texas, United States

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Teva Investigational Site 69

El Paso, Texas, United States

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Teva Investigational Site 45

San Antonio, Texas, United States

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Teva Investigational Site 121

Ciudad Autonoma de Buenos Aire, Argentina

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Teva Investigational Site 126

Ciudad Autonoma de Buenos Aire, Argentina

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Teva Investigational Site 123

Rosario-Santa Fe, Argentina

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Teva Investigational Site 120

San Miguel de Tucuman - Tucuma, Argentina

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Teva Investigational Site 150

Florianópolis, Brazil

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Teva Investigational Site 140

Porto Alegre, Brazil

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Teva Investigational Site 144

Porto Alegre, Brazil

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Teva Investigational Site 145

Porto Alegre, Brazil

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Teva Investigational Site 143

Porto Alegre, RS, Brazil

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Teva Investigational Site 142

Santo André, Brazil

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Teva Investigational Site 104

Newmarket, Canada

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Teva Investigational Site 102

Pointe-Claire, Canada

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Teva Investigational Site 105

Windsor, Canada

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Teva Investigational Site 343

Grenoble, France

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Teva Investigational Site 342

Marseille, France

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Teva Investigational Site 341

Montpellier, France

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Teva Investigational Site 360

Bad Wörishofen, Germany

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Teva Investigational Site 361

Berlin, Germany

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Teva Investigational Site 362

Berlin, Germany

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Teva Investigational Site 366

Berlin, Germany

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Teva Investigational Site 371

Bochum, Germany

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Teva Investigational Site 365

Dresden, Germany

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Teva Investigational Site 369

Frankfurt, Germany

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Teva Investigational Site 370

Hamburg, Germany

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Teva Investigational Site 372

Koblenz, Germany

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Teva Investigational Site 367

Leipzig, Germany

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Teva Investigational Site 368

Leipzig, Germany

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Teva Investigational Site 363

Mainz, Germany

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Teva Investigational Site 364

Mainz, Germany

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Teva Investigational Site 381

Alexandroupoli, Greece

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Teva Investigational Site 380

Athens, Greece

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Teva Investigational Site 382

Heraklion, Crete, Greece

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Teva Investigational Site 203

Distrito Federal, Mexico

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Teva Investigational Site 204

Guadalajara, JAL, Mexico

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Teva Investigational Site 205

Mexico City, Mexico

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Teva Investigational Site 207

Mexico City, Mexico

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Teva Investigational Site 209

Monterrey, Mexico

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Teva Investigational Site 202

Tijuana, B.C., Mexico

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Teva Investigational Site 223

Cercado de Lima, Lima, Peru

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Teva Investigational Site 220

Lima, Peru

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Teva Investigational Site 221

Lima, Peru

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Teva Investigational Site 222

Lima, Peru

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Teva Investigational Site 225

Lima, Peru

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Teva Investigational Site 226

Lima, Peru

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Teva Investigational Site 227

Lima, Peru

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Teva Investigational Site 229

Lima, Peru

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Teva Investigational Site 523

Bucharest, Romania

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Teva Investigational Site 524

Bucharest, Romania

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Teva Investigational Site 520

Cluj-Napoca, Romania

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Teva Investigational Site 521

Iași, Romania

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Teva Investigational Site 522

Târgu Mureş, Romania

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Teva Investigational Site 543

Moscow, Russia

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Teva Investigational Site 544

Moscow, Russia

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Teva Investigational Site 554

Moscow, Russia

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Teva Investigational Site 556

Moscow, Russia

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Teva Investigational Site 558

Moscow, Russia

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Teva Investigational Site 559

Moscow, Russia

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Teva Investigational Site 557

Novosibirsk, Russia

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Teva Investigational Site 540

Saint Petersburg, Russia

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Teva Investigational Site 541

Saint Petersburg, Russia

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Teva Investigational Site 563

Bradejov, Slovakia

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Teva Investigational Site 561

Levice, Slovakia

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Teva Investigational Site 560

Spišská Nová Ves, Slovakia

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Teva Investigational Site 562

Topoľčany, Slovakia

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Teva Investigational Site 682

Gwangju, South Korea

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Teva Investigational Site 680

Seoul, South Korea

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Teva Investigational Site 681

Seoul, South Korea

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Teva Investigational Site 683

Seoul, South Korea

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Teva Investigational Site 686

Seoul, South Korea

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Teva Investigational Site 685

Suwon, South Korea

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Teva Investigational Site 764

Kaohsiung City, Taiwan

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Teva Investigational Site 765

Taichung, Taiwan

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Teva Investigational Site 760

Taipei, Taiwan

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Teva Investigational Site 761

Taipei, Taiwan

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Teva Investigational Site 763

Taoyuan District, Taiwan

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Teva Investigational Site 621

Dnipropetrovsk, Ukraine

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Teva Investigational Site 629

Donetsk, Ukraine

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Teva Investigational Site 635

Donetsk, Ukraine

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Teva Investigational Site 630

Ivano-Frankivsk, Ukraine

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Teva Investigational Site 620

Kharkiv, Ukraine

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Teva Investigational Site 633

Kharkiv, Ukraine

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Teva Investigational Site 622

Kyiv, Ukraine

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Teva Investigational Site 623

Kyiv, Ukraine

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Teva Investigational Site 624

Kyiv, Ukraine

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Teva Investigational Site 625

Kyiv, Ukraine

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Teva Investigational Site 628

Ternopil, Ukraine

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Teva Investigational Site 626

Vinnytsia, Ukraine

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Teva Investigational Site 631

Zaporizhzhia, Ukraine

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Teva Investigational Site 632

Zaporizhzhia, Ukraine

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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 25, 2011
• First Posted: January 28, 2011
• Study Start: March 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: November 9, 2021
• Results First Posted: June 27, 2016

Record last verified: 2021-11

Locations

DE (13); TW (5); UA (14); CA (3); BR (6); AR (4); SL (4); ME (6); FR (3); RU (9); GR (3); US (15); RO (5); PE (8); KR (6)