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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
Results First Received: May 31, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Asthma
Interventions: Biological: Benralizumab 2 mg
Biological: Benralizumab 20 mg
Biological: Benralizumab 100 mg
Other: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were stratified based on the protocol defined eosinophilic phenotype (EOS+ versus EOS-) and inhaled corticosteroid (ICS) use during a 3-week screening period. A total of 964 participants were screened out of which 609 were randomized in the study, and of which 606 participants received at least one dose of investigational product.

Reporting Groups
  Description
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 subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS+ Benralizumab, 2 mg EOS+ participants received benralizumab 2 milligram (mg) subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS+ Benralizumab, 20 mg EOS+ participants received benralizumab 20 mg subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS+ Benralizumab, 100 mg EOS+ participants received benralizumab 50 mg as two subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Non-eosinophil Phenotype (EOS-) Placebo EOS- (defined as ELEN Index negative and FeNO <50 ppb) participants received matching placebo subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS- Benralizumab, 100 mg EOS- participants received benralizumab 50 mg as two subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Participant Flow:   Overall Study
    Eosinophilic Phenotype (EOS+) Placebo   EOS+ Benralizumab, 2 mg   EOS+ Benralizumab, 20 mg   EOS+ Benralizumab, 100 mg   Non-eosinophil Phenotype (EOS-) Placebo   EOS- Benralizumab, 100 mg
STARTED   80   81   81   82   142   140 
COMPLETED   69   73   70   69   129   125 
NOT COMPLETED   11   8   11   13   13   15 
Lost to Follow-up                4                2                3                1                1                2 
Unplanned surgery                1                0                0                0                0                0 
Did not meet entry ACQ-6 criteria                0                0                1                0                1                1 
Incorrect enrollment/randomization                0                0                1                0                1                0 
Subject traveled to Argentina by 1 year                0                0                1                0                0                0 
Subject moved out of state/area                0                0                1                1                0                0 
Strongyloides stercoralis antibodies +                0                0                0                1                0                0 
Personal problems                0                0                0                1                0                0 
Unable to continue visits                0                0                0                1                0                1 
Serious adverse event                0                0                0                0                0                1 
Lack of compliance                0                0                0                0                0                1 
Adverse Event                0                1                0                0                0                0 
Withdrawal by Subject                6                5                4                8                10                9 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The modified intent-to-treat (mITT) population included all randomized participants who received any dose of investigational product.

Reporting Groups
  Description
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 subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS+ Benralizumab, 2 mg EOS+ participants received benralizumab 2 milligram (mg) subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS+ Benralizumab, 20 mg EOS+ participants received benralizumab 20 mg subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS+ Benralizumab, 100 mg EOS+ participants received benralizumab 50 mg as two subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Non-eosinophil Phenotype (EOS-) Placebo EOS- (defined as ELEN Index negative and FeNO <50 ppb) participants received matching placebo subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
EOS- Benralizumab, 100 mg EOS- participants received benralizumab 50 mg as two subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Total Total of all reporting groups

Baseline Measures
   Eosinophilic Phenotype (EOS+) Placebo   EOS+ Benralizumab, 2 mg   EOS+ Benralizumab, 20 mg   EOS+ Benralizumab, 100 mg   Non-eosinophil Phenotype (EOS-) Placebo   EOS- Benralizumab, 100 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 80   81   81   82   142   140   606 
Age 
[Units: Years]
Mean (Standard Deviation)
 45.6  (11.7)   47.1  (12.8)   46.6  (13.2)   47.8  (12.9)   50.0  (12.3)   50.0  (11.5)   48.3  (12.4) 
Gender 
[Units: Participants]
             
Female   53   58   48   60   100   98   417 
Male   27   23   33   22   42   42   189 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants   [ Time Frame: Week 1 up to Week 52 ]

2.  Secondary:   Dose Response in EOS+ Participants   [ Time Frame: Baseline up to Week 66 ]

3.  Secondary:   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 ]

4.  Secondary:   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 ]

5.  Secondary:   Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants   [ Time Frame: Baseline up to Week 92 ]

6.  Secondary:   Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52   [ Time Frame: Baseline up to Week 52 ]

7.  Secondary:   Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52   [ Time Frame: Baseline up to Week 52 ]

8.  Secondary:   Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52   [ Time Frame: Baseline up to Week 51-52 ]

9.  Secondary:   Change From Baseline in Rescue Medication Use at Week 51-52   [ Time Frame: Baseline up to Week 51-52 ]

10.  Secondary:   Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52   [ Time Frame: Baseline and Week 52 ]

11.  Secondary:   Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52   [ Time Frame: Baseline and Week 52 ]

12.  Secondary:   Change From Baseline in Peak Expiratory Flow (PEF) at Week 52   [ Time Frame: Baseline and Week 52 ]

13.  Secondary:   Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52   [ Time Frame: Baseline and Week 52 ]

14.  Secondary:   Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52   [ Time Frame: Baseline and Week 52 ]

15.  Secondary:   Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52   [ Time Frame: Baseline and Week 52 ]

16.  Secondary:   Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52   [ Time Frame: Baseline up to Week 51-52 ]

17.  Secondary:   Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52   [ Time Frame: Baseline up to Week 52 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Rene van der Merwe, MBChB, MFPM, Medical Officer
Organization: MedImmune, LLC
phone: 301-398-0000
e-mail: vandermerwer@medimmune.com


Publications of Results:

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01238861     History of Changes
Other Study ID Numbers: MI-CP220
2010-020126-17 ( EudraCT Number )
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