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

NCT ID: NCT01287039

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 489 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-03-31

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.

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 (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.

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 (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.

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.
• 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.

• 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 58

Scottsdale, Arizona, United States

Teva Investigational Site 61

Los Angeles, California, United States

Teva Investigational Site 37

Orange, California, United States

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San Diego, California, United States

Teva Investigational Site 34

Colorado Springs, Colorado, United States

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DeBary, Florida, United States

Teva Investigational Site 55

Miami, Florida, United States

Teva Investigational Site 18

Valrico, Florida, United States

Teva Investigational Site 49

Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

Teva Investigational Site 35

Missoula, Montana, United States

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Boys Town, Nebraska, United States

Teva Investigational Site 68

Rochester, New York, United States

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The Bronx, New York, United States

Teva Investigational Site 30

Winston-Salem, North Carolina, United States

Teva Investigational Site 31

Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Altoona, Pennsylvania, United States

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Nashville, Tennessee, United States

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Boerne, Texas, United States

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Houston, Texas, United States

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Richmond, Virginia, United States

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Madison, Wisconsin, United States

Teva Investigational Site 643

Nedlands, Western Australia, Australia

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Clayton, , Australia

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Daw Park, , Australia

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Frankston, , Australia

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Liverpool, , Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Jambes, , Belgium

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Liège, , Belgium

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Rancagua, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Valdivia, , Chile

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Valparaíso, , Chile

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Bogotá, , Colombia

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Bogotá, , Colombia

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Cali, , Colombia

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Floridablanca, , Colombia

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Brno, , Czechia

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Břeclav, , Czechia

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Liberec, , Czechia

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Olomouc, , Czechia

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Olomouc, , Czechia

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Olomouc, , Czechia

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Tábor, , Czechia

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Hvidovre, , Denmark

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Odense, , Denmark

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Balassagyarmat, , Hungary

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Miskolc, , Hungary

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Mosonmagyaróvár, , Hungary

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Sopron, , Hungary

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Törökbálint, , Hungary

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Ashkelon, , Israel

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Beersheba, , Israel

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Haifa, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Ramat Gan, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Batu Caves, , Malaysia

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George Town, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuantan, , Malaysia

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Taiping, , Malaysia

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Christchurch, , New Zealand

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Dunedin, , New Zealand

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Hamilton, , New Zealand

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Tauranga, , New Zealand

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Wellington, , New Zealand

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Governor Mangubat Drive, Dasma, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Bystra, , Poland

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Ostrów Wielkopolski, , Poland

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Poznan, , Poland

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Sopot, , Poland

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Tarnów, , Poland

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Barnaul, , Russia

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Kazan', , Russia

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Kemerovo, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Saint Petersburg, , Russia

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Tomsk, , Russia

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Yaroslavl, , Russia

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Cape Town, , South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Centurion, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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Pretoria, , South Africa

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Pretoria, , South Africa

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Gothenburg, , Sweden

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Gothenburg, , Sweden

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Linköping, , Sweden

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Malmo, , Sweden

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Muang, , Thailand

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Nakhon Ratchasima, , Thailand

Countries

Netherlands; United States; Australia; Belgium; Chile; Colombia; Czechia; Denmark; Hungary; Israel; Malaysia; New Zealand; Philippines; Poland; Russia; South Africa; Sweden; Thailand

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

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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

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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.

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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

C38072/3082

Identifier Type: -

Identifier Source: org_study_id