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

This study has been completed.
Sponsor:
Collaborator:
MedImmune Ltd
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01238861
First received: November 9, 2010
Last updated: September 28, 2016
Last verified: September 2016
  Purpose
The primary objective of the study is to evaluate the effect of multiple-dose subcutaneous administrations of MEDI-563 on adults with uncontrolled asthma.

Condition Intervention Phase
Asthma
Biological: Benralizumab 2 mg
Biological: Benralizumab 20 mg
Biological: Benralizumab 100 mg
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma

Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants [ Time Frame: Week 1 up to Week 52 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Dose Response in EOS+ Participants [ Time Frame: Baseline up to Week 66 ] [ Designated as safety issue: No ]
  • Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss) [ Time Frame: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52 ] [ Designated as safety issue: No ]
  • Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD) [ Time Frame: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants [ Time Frame: Baseline up to Week 92 ] [ Designated as safety issue: No ]
    Immunogenicity assessment included determination of anti-drug (benralizumab) antibodies in serum samples. ADA positive was defined as a titer >=50 at any point in the study. It was observed at baseline and any visit during the study.

  • Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    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 was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. ACQ-6 score was summarized together for all participants.

  • Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    Total Nasal Symptoms Score (TNSS) is a 3-item questionnaire, the sum of nasal symptoms, namely, nasal obstruction (rhinorrhea), nasal congestion, and nasal itching/sneezing. Each symptom was rated on a scale from 0-3, with 0 representing no symptoms, 1 mild, 2 moderate, and 3 severe symptoms. TNSS score was a summation of the 3 individual nasal symptom. TNSS score could range from 0 to 9 where higher score indicates worsening. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 [ Time Frame: Baseline up to Week 51-52 ] [ Designated as safety issue: No ]
    Asthma Symptom Diary included 7 questions about the participant symptom and the overall impact of treatment on the disease during the study period. Mean scores of the 7 questions were calculated to identify asthma symptom-free days. Asthma Symptom Diary Scores were analyzed on a bi-weekly basis and compared to baseline scores. Overall symptom score=(daytime frequency score + daytime severity score + nighttime severity score)/3, where total score ranges from 0 to 9. Higher score represents worsening. Mean asthma symptom diary score were summarized together for all participants. Mean asthma symptom diary score were summarized together for all participants. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in Rescue Medication Use at Week 51-52 [ Time Frame: Baseline up to Week 51-52 ] [ Designated as safety issue: No ]
    Participants were provided inhalers of the same dose (medium- or high-dose) inhaled corticosteroid (ICS) plus long-acting beta antagonist (LABA) combination product as baseline prophylactic medication and continued with same dose throughout the study. Rescue medications such as short-term beta2 agonists were used as first-line treatment for worsening asthma symptoms. Investigator prescribed additional short term asthma controller medications included additional ICS, theophylline, inhaled cromones or antimuscarinics; if asthma symptoms remained mild but not resolved. If asthma symptoms worsened, participants received an oral corticosteroid burst. All rescue medications use with prophylactic medication (+ prophylactic) and without prophylactic medication (- prophylactic) was recorded in asthma symptom dairy by participant. Rescue medication use was analyzed on a bi-weekly basis and compared to baseline scores.

  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Forced Vital Capacity (FVC) was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  • Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed while sitting or standing prior to using any medication (if needed) for asthma. Home PEF was determined separately for morning and evening, and were averaged for each participant. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma 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). The AQLQ(S) responses were categorized as improvement (defined as change from baseline >=0.5), no change (defined as change from baseline >= -0.5 to less than [<] 0.5), and worse (defined as change from baseline < -0.5). Data was summarized by each treatment group.

  • Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems). Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 [ Time Frame: Baseline up to Week 51-52 ] [ Designated as safety issue: No ]
    Percentage of nocturnal awakening-free nights were analyzed on a bi-weekly basis and compared to baseline scores. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.

  • Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.


Enrollment: 964
Study Start Date: December 2010
Study Completion Date: August 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.
Other: Placebo
EOS+ and EOS- participants received two placebo injections subcutaneously.
Experimental: 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.
Biological: Benralizumab 2 mg
EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.
Other Name: MEDI-563
Experimental: 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.
Biological: Benralizumab 20 mg
EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.
Other Name: MEDI-563
Experimental: 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.
Biological: Benralizumab 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Other Name: MEDI-563
Placebo Comparator: 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.
Other: Placebo
EOS+ and EOS- participants received two placebo injections subcutaneously.
Experimental: 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.
Biological: Benralizumab 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Other Name: MEDI-563

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01238861

  Show 79 Study Locations
Sponsors and Collaborators
MedImmune LLC
MedImmune Ltd
Investigators
Study Director: Donald Raible, MD MedImmune LLC
  More Information

Additional Information:
Publications:
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01238861     History of Changes
Other Study ID Numbers: MI-CP220  2010-020126-17 
Study First Received: November 9, 2010
Results First Received: May 31, 2016
Last Updated: September 28, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Asthma
Benralizumab
MEDI-563

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on December 05, 2016