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

NCT ID: NCT01285323

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 464 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-04-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Reslizumab 3.0 mg/kg

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

Group Type: EXPERIMENTAL

Reslizumab

Intervention Type: 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.

Interventions

Reslizumab

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Cinquil; humanized monoclonal antibody; CEP-38072

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Expert, MD

Role: STUDY_DIRECTOR

Teva Branded Pharmaceutical Products R&D, Inc.

Locations

Teva Investigational Site 48

Mobile, Alabama, United States

Teva Investigational Site 41

Fresno, California, United States

Teva Investigational Site 59

Long Beach, California, United States

Teva Investigational Site 47

Denver, Colorado, United States

Teva Investigational Site 28

Waterbury, Connecticut, United States

Teva Investigational Site 53

Clearwater, Florida, United States

Teva Investigational Site 27

Miami, Florida, United States

Teva Investigational Site 25

Lawrenceville, Georgia, United States

Teva Investigational Site 57

Metairie, Louisiana, United States

Teva Investigational Site 46

Bangor, Maine, United States

Teva Investigational Site 40

St Louis, Missouri, United States

Teva Investigational Site 67

Fort Mill, South Carolina, United States

Teva Investigational Site 44

Dallas, Texas, United States

Teva Investigational Site 69

El Paso, Texas, United States

Teva Investigational Site 45

San Antonio, Texas, United States

Teva Investigational Site 121

Ciudad Autonoma de Buenos Aire, , Argentina

Teva Investigational Site 126

Ciudad Autonoma de Buenos Aire, , Argentina

Teva Investigational Site 123

Rosario-Santa Fe, , Argentina

Teva Investigational Site 120

San Miguel de Tucuman - Tucuma, , Argentina

Teva Investigational Site 150

Florianópolis, , Brazil

Teva Investigational Site 140

Porto Alegre, , Brazil

Teva Investigational Site 144

Porto Alegre, , Brazil

Teva Investigational Site 145

Porto Alegre, , Brazil

Teva Investigational Site 143

Porto Alegre, RS, , Brazil

Teva Investigational Site 142

Santo André, , Brazil

Teva Investigational Site 104

Newmarket, , Canada

Teva Investigational Site 102

Pointe-Claire, , Canada

Teva Investigational Site 105

Windsor, , Canada

Teva Investigational Site 343

Grenoble, , France

Teva Investigational Site 342

Marseille, , France

Teva Investigational Site 341

Montpellier, , France

Teva Investigational Site 360

Bad Wörishofen, , Germany

Teva Investigational Site 361

Berlin, , Germany

Teva Investigational Site 362

Berlin, , Germany

Teva Investigational Site 366

Berlin, , Germany

Teva Investigational Site 371

Bochum, , Germany

Teva Investigational Site 365

Dresden, , Germany

Teva Investigational Site 369

Frankfurt, , Germany

Teva Investigational Site 370

Hamburg, , Germany

Teva Investigational Site 372

Koblenz, , Germany

Teva Investigational Site 367

Leipzig, , Germany

Teva Investigational Site 368

Leipzig, , Germany

Teva Investigational Site 363

Mainz, , Germany

Teva Investigational Site 364

Mainz, , Germany

Teva Investigational Site 381

Alexandroupoli, , Greece

Teva Investigational Site 380

Athens, , Greece

Teva Investigational Site 382

Heraklion, Crete, , Greece

Teva Investigational Site 203

Distrito Federal, , Mexico

Teva Investigational Site 204

Guadalajara, JAL, , Mexico

Teva Investigational Site 205

Mexico City, , Mexico

Teva Investigational Site 207

Mexico City, , Mexico

Teva Investigational Site 209

Monterrey, , Mexico

Teva Investigational Site 202

Tijuana, B.C., , Mexico

Teva Investigational Site 223

Cercado de Lima, Lima, , Peru

Teva Investigational Site 220

Lima, , Peru

Teva Investigational Site 221

Lima, , Peru

Teva Investigational Site 222

Lima, , Peru

Teva Investigational Site 225

Lima, , Peru

Teva Investigational Site 226

Lima, , Peru

Teva Investigational Site 227

Lima, , Peru

Teva Investigational Site 229

Lima, , Peru

Teva Investigational Site 523

Bucharest, , Romania

Teva Investigational Site 524

Bucharest, , Romania

Teva Investigational Site 520

Cluj-Napoca, , Romania

Teva Investigational Site 521

Iași, , Romania

Teva Investigational Site 522

Târgu Mureş, , Romania

Teva Investigational Site 543

Moscow, , Russia

Teva Investigational Site 544

Moscow, , Russia

Teva Investigational Site 554

Moscow, , Russia

Teva Investigational Site 556

Moscow, , Russia

Teva Investigational Site 558

Moscow, , Russia

Teva Investigational Site 559

Moscow, , Russia

Teva Investigational Site 557

Novosibirsk, , Russia

Teva Investigational Site 540

Saint Petersburg, , Russia

Teva Investigational Site 541

Saint Petersburg, , Russia

Teva Investigational Site 563

Bradejov, , Slovakia

Teva Investigational Site 561

Levice, , Slovakia

Teva Investigational Site 560

Spišská Nová Ves, , Slovakia

Teva Investigational Site 562

Topoľčany, , Slovakia

Teva Investigational Site 682

Gwangju, , South Korea

Teva Investigational Site 680

Seoul, , South Korea

Teva Investigational Site 681

Seoul, , South Korea

Teva Investigational Site 683

Seoul, , South Korea

Teva Investigational Site 686

Seoul, , South Korea

Teva Investigational Site 685

Suwon, , South Korea

Teva Investigational Site 764

Kaohsiung City, , Taiwan

Teva Investigational Site 765

Taichung, , Taiwan

Teva Investigational Site 760

Taipei, , Taiwan

Teva Investigational Site 761

Taipei, , Taiwan

Teva Investigational Site 763

Taoyuan District, , Taiwan

Teva Investigational Site 621

Dnipropetrovsk, , Ukraine

Teva Investigational Site 629

Donetsk, , Ukraine

Teva Investigational Site 635

Donetsk, , Ukraine

Teva Investigational Site 630

Ivano-Frankivsk, , Ukraine

Teva Investigational Site 620

Kharkiv, , Ukraine

Teva Investigational Site 633

Kharkiv, , Ukraine

Teva Investigational Site 622

Kyiv, , Ukraine

Teva Investigational Site 623

Kyiv, , Ukraine

Teva Investigational Site 624

Kyiv, , Ukraine

Teva Investigational Site 625

Kyiv, , Ukraine

Teva Investigational Site 628

Ternopil, , Ukraine

Teva Investigational Site 626

Vinnytsia, , Ukraine

Teva Investigational Site 631

Zaporizhzhia, , Ukraine

Teva Investigational Site 632

Zaporizhzhia, , Ukraine

Countries

India; United States; Argentina; Brazil; Canada; France; Germany; Greece; Mexico; Peru; Romania; Russia; Slovakia; South Korea; Taiwan; Ukraine

References

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.

Reference Type: DERIVED

PMID: 31626990 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31262379 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30964365 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30346831 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30193936 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28159511 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25736990 (View on PubMed)

Other Identifiers

2010-024006-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C38072/3083

Identifier Type: -

Identifier Source: org_study_id