Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma

NCT ID: NCT01238861

Last Updated: 2016-11-17

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

964 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-31

Study Completion Date

2013-08-31

Brief Summary

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The primary objective of the study is to evaluate the effect of multiple-dose subcutaneous administrations of MEDI-563 on adults with uncontrolled asthma.

Detailed Description

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This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of multiple-dose (7 doses) subcutaneous administration of benralizumab (MEDI-563) in adult subjects with uncontrolled asthma.

Conditions

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Asthma

Keywords

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Asthma Benralizumab MEDI-563

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Eosinophilic phenotype (EOS+) Placebo

EOS+ (defined as ELEN Index \[proprietary mathematical algorithm to predict sputum eosinophil's greater than or equal to 2 percent\] positive and/or FeNO \[fraction of exhaled nitric oxide\] greater than or equal to \[\>=\] 50 parts per billion \[ppb\]) participants received matching placebo injections subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

EOS+ and EOS- participants received two placebo injections subcutaneously.

EOS+ Benralizumab (2 mg)

EOS+ participants received single benralizumab 2 milligram (mg) injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Group Type EXPERIMENTAL

Benralizumab 2 mg

Intervention Type BIOLOGICAL

EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.

EOS+ Benralizumab (20 mg)

EOS+ participants received single benralizumab 20 mg injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Group Type EXPERIMENTAL

Benralizumab 20 mg

Intervention Type BIOLOGICAL

EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.

EOS+ Benralizumab (100 mg)

EOS+ participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Group Type EXPERIMENTAL

Benralizumab 100 mg

Intervention Type BIOLOGICAL

EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.

Non-eosinophil phenotype (EOS-) Placebo

EOS- (defined as ELEN Index negative and FeNO \<50 ppb) participants received matching placebo subcutaneous every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

EOS+ and EOS- participants received two placebo injections subcutaneously.

EOS- Benralizumab (100 mg)

EOS- participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Group Type EXPERIMENTAL

Benralizumab 100 mg

Intervention Type BIOLOGICAL

EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.

Interventions

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Benralizumab 2 mg

EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.

Intervention Type BIOLOGICAL

Benralizumab 20 mg

EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.

Intervention Type BIOLOGICAL

Benralizumab 100 mg

EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.

Intervention Type BIOLOGICAL

Placebo

EOS+ and EOS- participants received two placebo injections subcutaneously.

Intervention Type OTHER

Other Intervention Names

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MEDI-563 MEDI-563 MEDI-563

Eligibility Criteria

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Inclusion Criteria

* Age 18 through 75 years at the time of screening
* Adequate contraception from screening through end of trial
* Weight of more than (\>) 45 kilogram (kg) but less than or equal to (\<=) 150 kg (\>100 pound \[lb\] but \<=330 lb)
* History of physician-diagnosed asthma for at least 12 months prior to screening
* Physician prescribed daily use of medium-dose or high-dose inhaled corticosteroid(s) (ICS) plus long-acting beta 2 agonist (LABA) for at least 12 months prior to screening
* Willingness to switch to an ICS/LABA combination product
* Dose of other asthma controller medications must be stable for at least 30 days prior to screening
* At least 2 documented asthma exacerbations in the 12 months prior to screening that required use of a systemic corticosteroid burst
* For subjects 65 years of age or older, a chest x-ray (CXR) or chest computed tomography (CT) that is normal for an asthmatic population
* Ability and willingness to complete the study to Week 66, and if needed to Week 92.

Exclusion Criteria

* Known history of allergy or reaction to any component of the investigational product formulation
* History of anaphylaxis to any biologic therapy
* Unexplained diarrhea within 30 days prior to screening or diagnosis of helminth parasitic infestation within 6 months prior to screening
* Use of immunosuppressive medication within 3 months prior to screening. Chronic oral prednisone or equivalent up to 10 milligram (mg) daily or 20 mg every other day for asthma is allowed
* Oral corticosteroid burst or short-acting systemic corticosteroid within 30 days prior to screening or during the screening/run-in period
* Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to the screening or during the screening/run-in period
* Receipt of immunoglobulin or blood products within 30 days prior to screening
* Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to screening, whichever is longer
* Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to screening, whichever is longer
* Previously received MEDI-563
* Any clinically relevant abnormal findings in physical examination
* Past history of clinically significant cardiac disease or any electrocardiogram (ECG) abnormality
* Breastfeeding or lactating women
* History of alcohol or drug abuse within 12 months prior to screening
* History of any known primary immunodeficiency disorder
* Positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol
* A positive human immunodeficiency virus (HIV) test or subject taking antiretroviral medications
* History of cigarette smoking more than or equal to (\>=) 10 pack-years or smoking within 12 months prior to screening.
* Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma
* History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy \>=12 months prior to screening or other malignancies treated with apparent success with curative therapy \>=5 years prior to screening
* Stable dose of allergy vaccination regimen for less than 30 days prior to screening
* Subjects unable to demonstrate acceptable inhaler and peak flow meter techniques.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune Ltd

INDUSTRY

Sponsor Role collaborator

MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Donald Raible, MD

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

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Birmingham, Alabama, United States

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Los Angeles, California, United States

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Orange, California, United States

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San Diego, California, United States

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Stockton, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Waterbury, Connecticut, United States

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Kissimmee, Florida, United States

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Tampa, Florida, United States

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Stockbridge, Georgia, United States

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Normal, Illinois, United States

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Baltimore, Maryland, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Bellevue, Nebraska, United States

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Summit, New Jersey, United States

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Rochester, New York, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Blue Bell, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Warwick, Rhode Island, United States

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Boerne, Texas, United States

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San Antonio, Texas, United States

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Seattle, Washington, United States

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Caba, , Argentina

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Ciudad de Buenos Aires, , Argentina

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San Miguel de Tucumán, , Argentina

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Santa Fe, , Argentina

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Juiz de Fora, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Salvador, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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Pleven, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Troyan Municipality, , Bulgaria

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Brampton, Ontario, Canada

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Toronto, Ontario, Canada

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La Malbaie, Quebec, Canada

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Québec, Quebec, Canada

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Bogotá, , Colombia

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Guadalajara, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Morelia, , Mexico

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Villahermosa, , Mexico

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Zapopan, , Mexico

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Lima, , Peru

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San Borja, , Peru

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San Isidro, , Peru

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Surco, , Peru

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Ostrów Wielkopolski, , Poland

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Piła, , Poland

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Poznan, , Poland

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Tarnów, , Poland

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Warsaw, , Poland

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Barnaul, , Russia

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Chelyabinsk, , Russia

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Kazan', , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Saint Petersburg, , Russia

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Yekaterinburg, , Russia

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Countries

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South Africa United States Argentina Brazil Bulgaria Canada Colombia Mexico Peru Poland Russia

References

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Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, Gossage DL, Ward CK, Wu Y, Wang B, Khatry DB, van der Merwe R, Kolbeck R, Molfino NA, Raible DG. Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014 Nov;2(11):879-890. doi: 10.1016/S2213-2600(14)70201-2. Epub 2014 Oct 8.

Reference Type RESULT
PMID: 25306557 (View on PubMed)

Sridhar S, Liu H, Pham TH, Damera G, Newbold P. Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases. Respir Res. 2019 Jan 18;20(1):14. doi: 10.1186/s12931-018-0968-8.

Reference Type DERIVED
PMID: 30658649 (View on PubMed)

Other Identifiers

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2010-020126-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MI-CP220

Identifier Type: -

Identifier Source: org_study_id