Clinical trial NCT00768079: A Phase 2 Study to Evaluate the Safety and Efficacy of Intravenously Administered Benralizumab (MEDI-563).
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenously Administered MEDI-563, A Humanized Anti-interleukin-5 Receptor Alpha Monoclonal Antibody, on Asthma Control Following Acute Exacerbations in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Benralizumab
MEDI-563
Asthma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2008-10-07
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the effect of two intravenous dose regimens of benralizumab (MEDI-563) on the proportion of adult subjects with asthma exacerbations who required an urgent healthcare visit for treatment of an acute asthma exacerbation.

Detailed description: The study will evaluate the effect of two intravenous dose regimens of benralizumab (MEDI-563) (0.3 milligram per kilogram \[mg/kg\] of body weight and 1.0 mg/kg of body weight) on the proportion of adult subjects with asthma exacerbations (relapse and de novo) who required an urgent healthcare visit for treatment of an acute asthma exacerbation.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects aged 18 to 60 years at the time of the administration of investigational product
* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization (applies to covered entities in the US only) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
* Physician-diagnosed asthma with a duration of greater than or equal to (\>=) 2 years by medical chart or subject report
* Had an asthma exacerbation requiring urgent care in the year prior to screening
* Meets National Heart, Lung, and Blood Institute (NHLBI) for persistent asthma in the 3 months prior to the current urgent healthcare visit
* Current asthma exacerbation that must have lasted \>= 2 hours prior to arrival to the urgent healthcare setting
* Requires at least 2 treatments of inhaled bronchodilators for the current asthma exacerbation in the urgent healthcare setting or within the emergency medical system (EMS) for \>= 1 hour
* Shows an FEV1 or PEF of not more than 70 percent (%) predicted after 1 hour of treatment of the current asthma exacerbation
* Women of child-bearing potential, unless surgically sterile (including tubal ligation) and/or at least 2 years post-menopausal, must have used 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, abstinence, use of a condom with spermicide by the sexual partner, or sterile sexual partner) from screening through the end of the study (Day 84; Cessation of birth control after this point should be discussed with a responsible physician)
* Men, unless surgically sterile, must likewise practice 2 effective methods of birth control (condom with spermicide or abstinence) and must use such precautions from Day 0 through Day 84
* Otherwise healthy by medical history and physical examination
* A chest x-ray that is normal for an asthmatic population and excludes alternative diagnosis per the investigation
* Ability to complete the follow-up period until Day 168 as required by protocol
* The investigator has determined that the subject is clinically stable and the FEV1, is \>= 30% predicted prior to receiving investigational product on Day 0.

Exclusion Criteria:

* Known history of allergy or reaction to any component of the investigational product formulation
* Acute illness other than asthma at the start of the study
* Fever more than (\>) 38.6 degrees Celsius (C) (\>101.5 degrees Fahrenheit \[F\])
* Current acute asthma attack is due to aspirin-induced asthma
* Current asthma episode is an anaphylactoid/anaphylactic reaction presenting with acute bronchospasm
* Evidence of clinically significant non-respiratory active infection, including ongoing chronic infection
* History or current prolonged diarrhea, abdominal pain, and/or blood and mucus in stools or have minor symptoms and have exposure to stream or lake water, been exposed to someone who has a parasitic infection (like a family member), or study subject has traveled outside the United States of America (USA) and/or Canada within the last year
* Use of immunosuppressive medication (except oral prednisone and inhaled and topical corticosteroids) within 30 days before randomization into the study
* Have received Xolair within 6 months before randomization into the study
* Receipt of immunoglobulin or blood products within 30 days before randomization into the study
* Receipt of any investigational drug therapy within 6 months before the first dose of investigational product in this study through Day 168
* History of primary immunodeficiency
* Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the subject in the study
* History of clinically significant abnormality on ECG in the opinion of the investigator
* Pregnancy (must have a negative serum pregnancy test prior to the first dose of investigational product)
* Breastfeeding or lactating woman
* History of treatment for alcohol or drug abuse within the past year
* Diagnosis of chronic obstructive pulmonary disease (COPD) by a healthcare professional
* Evidence of any clinically significant systemic disease on physical examination
* History of cancer except basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy \>1 year prior to entry or other malignancies treated with apparent success with curative therapy \>5 years prior to entry
* Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma
* Any condition (that is, impending ventilatory failure or hemodynamic compromise) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of study results
* Any employee of the clinical study site who is involved with the conduct of the study
* History of cigarette smoking \>20 pack years
* Previously received benralizumab (MEDI-563)
* Asthma exacerbation due to acute inhalational exposure.

Primary outcomes:
measure: Percentage of Participants With Asthma Exacerbations at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 0 to Day 84
measure: Percentage of Participants With Asthma Exacerbations at Week 4 and Week 24
timeFrame: Weeks 4 and 24
measure: Asthma Control Questionnaire (ACQ) Scores
timeFrame: Days 0, 7, 42, and 84
measure: Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites
timeFrame: Days 0, 7, 42, and 84
measure: Forced Expiratory Volume in 1 Second (FEV1) Recorded at Home
timeFrame: Day 1 to Day 84
measure: Peak Expiratory Flow (PEF) Recorded at Home
timeFrame: Day 1 to Day 84
measure: Number of Puffs of Rescue Beta-2 Agonist Per Week
timeFrame: Day 1 to Day 84
measure: Number of Participants With Physician Global Assessment (PGA) at Day 42 and Day 84
timeFrame: Days 42 and 84
measure: Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores
timeFrame: Days 0, 42, and 84
measure: Number of Healthcare Resources Utilized by Resource Type
timeFrame: Day 0 to Day 168
measure: Maximum Observed Serum Concentration (Cmax) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUC [0 - Infinity]) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Systemic Clearance (CL) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Terminal Phase Elimination Half-Life (t1/2) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Volume of Distribution of the Central Compartment (Vc) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Volume of Distribution at Steady State (Vss) for Benralizumab
timeFrame: Predose and 1 hour post-end of infusion on Day 0; Days 7, 42, and 84
measure: Number of Participants With Anti-Drug Antibodies to Benralizumab
timeFrame: Day 0 and 84
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Springfield
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: East Meadow
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
Study officials:
affiliation: MedImmune LLC
name: Joseph M. Parker, M.D.
role: STUDY_DIRECTOR
References:
citation: Nowak RM, Parker JM, Silverman RA, Rowe BH, Smithline H, Khan F, Fiening JP, Kim K, Molfino NA. A randomized trial of benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, after acute asthma. Am J Emerg Med. 2015 Jan;33(1):14-20. doi: 10.1016/j.ajem.2014.09.036. Epub 2014 Oct 5.