Clinical trial NCT01238861: Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma
Official title: A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Benralizumab
MEDI-563
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: MedImmune Ltd
First posted: 2010-11-11
Enrollment: 964
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants
timeFrame: Week 1 up to Week 52
Secondary outcomes:
measure: Dose Response in EOS+ Participants
timeFrame: Baseline up to Week 66
measure: Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss)
timeFrame: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
measure: Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD)
timeFrame: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
measure: Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants
timeFrame: Baseline up to Week 92
measure: Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52
timeFrame: Baseline up to Week 52
measure: Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52
timeFrame: Baseline up to Week 52
measure: Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52
timeFrame: Baseline up to Week 51-52
measure: Change From Baseline in Rescue Medication Use at Week 51-52
timeFrame: Baseline up to Week 51-52
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Peak Expiratory Flow (PEF) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52
timeFrame: Baseline up to Week 51-52
measure: Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Stockton
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Stockbridge
country: United States
facility: Research Site
state: Georgia
city: Normal
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: St Louis
country: United States
facility: Research Site
state: Missouri
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Bellevue
country: United States
facility: Research Site
state: Nebraska
city: Summit
country: United States
facility: Research Site
state: New Jersey
city: Rochester
country: United States
facility: Research Site
state: New York
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Blue Bell
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Warwick
country: United States
facility: Research Site
state: Rhode Island
city: Boerne
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Caba
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Santa Fe
country: Argentina
facility: Research Site
city: Tucumán
country: Argentina
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
facility: Research Site
city: Juiz de Fora
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Santo André
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Troyan
country: Bulgaria
facility: Research Site
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: La Malbaie
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Bogotá
country: Colombia
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Morelia
country: Mexico
facility: Research Site
city: Villahermosa
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: San Borja
country: Peru
facility: Research Site
city: San Isidro
country: Peru
facility: Research Site
city: Surco
country: Peru
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Ostrów Wielkopolski
country: Poland
facility: Research Site
city: Pila
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Barnaul
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St-Petersburg
country: Russian Federation
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Donald Raible, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.