NCT01238861

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
964

participants targeted

Target at P75+ for phase_2 asthma

Timeline
Completed

Started Dec 2010

Longer than P75 for phase_2 asthma

Geographic Reach
10 countries

74 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 9, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 11, 2010

Completed
20 days until next milestone

Study Start

First participant enrolled

December 1, 2010

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
3.3 years until next milestone

Results Posted

Study results publicly available

November 17, 2016

Completed
Last Updated

November 17, 2016

Status Verified

September 1, 2016

Enrollment Period

2.2 years

First QC Date

November 9, 2010

Results QC Date

May 31, 2016

Last Update Submit

September 28, 2016

Conditions

Keywords

AsthmaBenralizumabMEDI-563

Outcome Measures

Primary Outcomes (1)

  • Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants

    The annual asthma exacerbation rate (AER) was calculated as the total number of observed exacerbations in each group up to week 52, divided by total duration of person-year follow-up in each group. An asthma exacerbation is defined as a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids (tablets, suspension or injection) for a duration of at least 3 days as outlined in the Asthma Action Plan provided to the participant by the investigator on Day 1.

    Week 1 up to Week 52

Secondary Outcomes (16)

  • Dose Response in EOS+ Participants

    Baseline up to Week 66

  • Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss)

    Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52

  • Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD)

    Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52

  • Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants

    Baseline up to Week 92

  • Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52

    Baseline up to Week 52

  • +11 more secondary outcomes

Study Arms (6)

Eosinophilic phenotype (EOS+) Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

EOS+ Benralizumab (2 mg)

EXPERIMENTAL

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.

Biological: Benralizumab 2 mg

EOS+ Benralizumab (20 mg)

EXPERIMENTAL

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.

Biological: Benralizumab 20 mg

EOS+ Benralizumab (100 mg)

EXPERIMENTAL

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.

Biological: Benralizumab 100 mg

Non-eosinophil phenotype (EOS-) Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

EOS- Benralizumab (100 mg)

EXPERIMENTAL

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.

Biological: Benralizumab 100 mg

Interventions

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

Also known as: MEDI-563
EOS+ Benralizumab (2 mg)

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

Also known as: MEDI-563
EOS+ Benralizumab (20 mg)

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

Also known as: MEDI-563
EOS+ Benralizumab (100 mg)EOS- Benralizumab (100 mg)
PlaceboOTHER

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

Eosinophilic phenotype (EOS+) PlaceboNon-eosinophil phenotype (EOS-) Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (74)

Research Site

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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Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

Asthma

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Results Point of Contact

Title
Rene van der Merwe, MBChB, MFPM, Medical Officer
Organization
MedImmune, LLC

Study Officials

  • Donald Raible, MD

    MedImmune LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2010

First Posted

November 11, 2010

Study Start

December 1, 2010

Primary Completion

March 1, 2013

Study Completion

August 1, 2013

Last Updated

November 17, 2016

Results First Posted

November 17, 2016

Record last verified: 2016-09

Locations