A Phase 2 Study to Evaluate the Safety and Efficacy of Intravenously Administered Benralizumab (MEDI-563).

MedImmune LLC110 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

110

Conditions

Asthma

Interventions

PlaceboOTHER

A single dose of placebo matched to benralizumab (MEDI-563) intravenous infusion over at least 30 minutes on Day 0.

BenralizumabBIOLOGICAL

A single dose of benralizumab (MEDI-563) 0.3 or 1 mg/kg of body weight intravenous infusion over at least 30 minutes on Day 0.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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.

Locations (11)

Research Site

Tampa, Florida, United States

Research Site

Springfield, Massachusetts, United States

Research Site

Detroit, Michigan, United States

Research Site

Outcomes

Primary Outcomes

Percentage of Participants With Asthma Exacerbations at Week 12

Percentage of participants who required urgent healthcare visit for treatment of acute asthma exacerbation were reported. As per protocol, asthma exacerbation (relapse/de novo) was defined as either 1) increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that did not resolve within 2 hours after use of rescue albuterol or corticosteroids and required an unscheduled medical visit or 2) during scheduled study visit, participant had acute worsening of asthma symptoms and a reduction of greater than or equal to (\>=) 20 percent (%) in Peak Expiratory Flow (PEF) or Forced Expiratory Volume in 1 Second (FEV1), which in the opinion of the investigator required treatment with systemic corticosteroids. Asthma exacerbations were analyzed in a non-adjudicated manner (by investigator), which were then adjudicated in a blinded fashion by the sponsor medical monitor prior to database lock to determine whether the reported exacerbation met the protocol definition.

Time frame: Week 12

Secondary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 84 that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Day 0 to Day 84

Percentage of Participants With Asthma Exacerbations at Week 4 and Week 24

Percentage of participants who required an urgent healthcare visit for treatment of an acute asthma exacerbation were reported. As per protocol, asthma exacerbation (relapse or de novo) was defined as either 1) an increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that did not resolve within 2 hours after the use of rescue albuterol or corticosteroids and required an unscheduled medical visit or 2) during a scheduled study visit, the participant had acute worsening of asthma symptoms and a reduction of \>=20% in PEF or FEV1, which in the opinion of the investigator required treatment with systemic corticosteroids. Asthma exacerbations were analyzed in a non-adjudicated manner (by investigator), which were then adjudicated in a blinded fashion by the sponsor medical monitor prior to database lock to determine whether the reported exacerbation met the protocol definition.

Data from ClinicalTrials.gov

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East Meadow, New York, United States

Research Site

New Hyde Park, New York, United States

Research Site

Stony Brook, New York, United States

Research Site

Greenville, North Carolina, United States

Research Site

Cleveland, Ohio, United States

Research Site

Providence, Rhode Island, United States

Research Site

Edmonton, Alberta, Canada

...and 1 more locations

Time frame: Weeks 4 and 24

Asthma Control Questionnaire (ACQ) Scores

Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Results were reported for overall ACQ score and 6 item scores.

Time frame: Days 0, 7, 42, and 84

Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites

The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Spirometry was performed with the participant in the sitting position at study sites by the investigator or qualified designee according to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Multiple forced expiratory efforts (at least 2 but no more than 5) were performed for each office spirometry session and the 2 best efforts that met ATS/ERS acceptability and reproducibility criteria were recorded. The best efforts were based on the highest FEV1. The maximum FEV1 of the 2 best efforts was used for the analysis.

Time frame: Days 0, 7, 42, and 84

Forced Expiratory Volume in 1 Second (FEV1) Recorded at Home

The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Home peak flow testing for FEV1 was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean FEV1 values for each week were reported starting from Day 1 to Day 84.

Time frame: Day 1 to Day 84

Peak Expiratory Flow (PEF) Recorded at Home

The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Home peak flow testing for PEF was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean PEF values for each week were reported starting from Day 1 to Day 84.

Time frame: Day 1 to Day 84

Number of Puffs of Rescue Beta-2 Agonist Per Week

Rescue beta-2 agonist use (total number of puffs for the prior day) was collected daily in the morning by the participants in the electronic daily diary provided to them. Participants were instructed not to collect rescue beta-2 agonist used prior to exercise. Average values for each week were reported starting from Day 1 to Day 84.

Time frame: Day 1 to Day 84

Number of Participants With Physician Global Assessment (PGA) at Day 42 and Day 84

Physician Global Assessment (PGA) consisted of a single physician-rated question assessing participant's status as 'excellent', 'good', 'moderate', 'poor', 'worsening' or 'not applicable (NA)'. Number of participants were categorically summarized.

Time frame: Days 42 and 84

Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores

Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ\[S\]): a 32-item questionnaire that measures the functional impairments experienced by adult participants including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment).

Time frame: Days 0, 42, and 84

Number of Healthcare Resources Utilized by Resource Type

Healthcare resource use was summarized by resource type from information on asthma exacerbations, and asthma related medications. Healthcare resource utilization assessed the total number of hospitalizations, urgent care, primary care clinic visits, asthma specialist clinic visits, telephone calls, and home management.

Time frame: Day 0 to Day 168

Maximum Observed Serum Concentration (Cmax) for Benralizumab

The Cmax of benralizumab is reported. Non-compartmental pharmacokinetic (PK) analysis was used for evaluation.