A Study of the Safety and Effectiveness of Benralizumab to Treat Patients With Severe Uncontrolled Asthma.
NCT ID: NCT03170271
Last Updated: 2021-11-01
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
660 participants
INTERVENTIONAL
2017-07-07
2020-10-21
Brief Summary
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Detailed Description
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After enrolment, eligible patients will enter an up to 42-day screening/run-in period. Patients who meet eligibility criteria will be randomized 2:1 on Day 0 to receive either benralizumab or placebo every 56 days (every 8 weeks) through Week 16, with end of treatment (EOT) at Day 168 (Week 24). At the completion of the 24-week doubleblind period of the ANDHI study, eligible patients in benralizumab and placebo arm may enter a 56-week open label period (ANDHI in Practice \[ANDHI IP\] substudy), in which concomitant asthma therapies will be tapered as directed by the protocol in those patients who achieve and maintain asthma control (defined as ACQ6 score \<1.5 and no clinically significant asthma exacerbations that required a burst of systemic corticosteroid or a hospitalization due to asthma between reduction visits) with add-on benralizumab.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Benralizumab (Medi-563)
Benralizumab (Medi563) Administered subcutaneously at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72).
Benralizumab (Medi-563)
30mg Benralizumab administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72).
Placebo
Administered subcutaneously at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days)
Placebo
Placebo administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days)
Interventions
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Benralizumab (Medi-563)
30mg Benralizumab administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72).
Placebo
Placebo administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days)
Eligibility Criteria
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Inclusion Criteria
2. Documented current treatment with high daily doses of ICS plus at least one other asthma controller for at least 3 months prior to Visit 1.
3. History of at least 2 asthma exacerbations while on ICS plus another asthma controller that required treatment with systemic corticosteroids (IM, IV, or oral) in the 12 months prior to Visit 1.
4. ACQ6 score ≥1.5 at Visit 1.
5. Screening pre-bronchodilator (pre-BD) FEV1 of \<80% predicted at Visit 2.
6. Excessive variability in lung function by satisfying ≥ 1 of the following criteria:
1. Airway reversibility (FEV1 ≥12%) using a short-acting bronchodilator demonstrated at Visit 2 or Visit 3.
2. Airway reversibility to short-acting bronchodilator (FEV1 ≥12%) documented during the 12 months prior to enrolment Visit 1.
3. Daily diurnal peak flow variability of \>10% when averaged over 7 continuous days during the study run-in period
4. An increase in FEV1 of ≥12% and 200 mL after a therapeutic trial of systemic corticosteroid (eg, OCS), given outside of an asthma exacerbation, documented in the 12 months prior enrolment Visit 1.
5. Airway hyper-responsiveness (methacholine: PC20 of \<8 mg/mL, histamine: PD20 of \<7.8 μmol, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to randomization Visit 4.
7. Peripheral blood eosinophil count either:
* 300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2
OR
≥150 to \<300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2, IF ≥1 of the following 5 clinical criteria (a to e) is met:
1. Using maintenance OCS (daily or every other day OCS requirement in order to maintain asthma control; maximum total daily dose 20 mg prednisone or equivalent) at screening
2. History of nasal polyposis
3. Age of asthma onset ≥18 years
4. Three or more documented exacerbations requiring systemic corticosteroid treatment during the 12 months prior to screening
5. Pre-bronchodilator forced vital capacity \<65% of predicted, as assessed at Visit 2 (note that screening pre-BD FEV1 Inclusion Criterion #6 must still be satisfied)
For inclusion in the open label ANDHI IP sub study patients should meet the following criteria:
1. Patients study must have completed ANDHI EOT Visit 11.
2. Written informed consent must also be obtained prior to any study related procedures being performed in the open label ANDHI IP sub study.
3. Patients who have received any approved or investigational targeted biologic for the treatment of asthma (e.g. commercial mepolizumab, reslizumab, benralizumab) may be included if the last dose is ≥ 2 months of Visit 13.
Exclusion Criteria
2. Acute upper or lower respiratory infections within 30 days prior to the date informed consent.
3. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
4. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
5. A history of known immunodeficiency disorder.
6. Current smokers or former smokers with a smoking history of ≥10 pack years.
7. Previously received benralizumab (MEDI-563).
8. Receipt of any investigational medication as part of a research study within approximately 5 half-lives prior to randomization.
9. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
10. Receipt of live attenuated vaccines 30 days prior to the date of randomization; other types of vaccines are allowed.
11. Concurrent enrolment in another interventional or post-authorization safety study
1. Patients who participated in the double-blind period but failed to complete the ANDHI EOT Visit 11. Patients who completed the ANDHI FU Visit 12 are not excluded from participation in the ANDHI IP sub study.
2. Unable to commit to the monthly visits as required by the protocol, or unable to commit to undergoing protocol guided reductions in asthma therapy, as directed by the Investigator.
3. Patients who experienced a severe or serious treatment-related AE during the double-blind period and, and those whom Investigator judges it is not in the patient's best interest to extend possible treatment with benralizumab.
4. Approved or off-label use of systemic immunosuppressive medications within 3 months prior to the first open label visit (Visit 13). These include but are not limited to small molecules such as methotrexate, cyclosporine, azathioprine, and immunosuppressive/immunomodulating biologics such as tumour necrosis factor (TNF) blockers. Regular use of systemic OCS is also excluded except for the indication of asthma.
5. Receipt of live attenuated vaccines 30 days prior to the first visit in the open label ANDHI IP sub study (Visit 13); other types of vaccines are allowed.
6. Planned surgical procedures during the conduct of the study.
7. Positive urine pregnancy test at Visit 13, or currently breastfeeding or lactating women.
18 Years
75 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Responsible Party
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Principal Investigators
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Brad Goodman, MD
Role: PRINCIPAL_INVESTIGATOR
Aero Allergy Research Lab of Savannah
Vinay Sikand, MD
Role: PRINCIPAL_INVESTIGATOR
Sikand Institute of Pulmonary Research
Willaim Cherry, MD
Role: PRINCIPAL_INVESTIGATOR
Riverside Medical Center
Locations
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Birmingham, Alabama, United States
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Tucson, Arizona, United States
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Little Rock, Arkansas, United States
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Bakersfield, California, United States
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Encinitas, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Mission Viejo, California, United States
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Newport Beach, California, United States
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Riverside, California, United States
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San Diego, California, United States
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Stockton, California, United States
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Walnut Creek, California, United States
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Aurora, Colorado, United States
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New Haven, Connecticut, United States
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Waterbury, Connecticut, United States
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Clearwater, Florida, United States
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Jacksonville, Florida, United States
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Kissimmee, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Winter Park, Florida, United States
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Albany, Georgia, United States
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Savannah, Georgia, United States
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Peoria, Illinois, United States
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South Bend, Indiana, United States
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Iowa City, Iowa, United States
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West Des Moines, Iowa, United States
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Lakeside Park, Kentucky, United States
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Owensboro, Kentucky, United States
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Shreveport, Louisiana, United States
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Chevy Chase, Maryland, United States
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White Marsh, Maryland, United States
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North Dartmouth, Massachusetts, United States
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Ann Arbor, Michigan, United States
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Ypsilanti, Michigan, United States
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Minneapolis, Minnesota, United States
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St Louis, Missouri, United States
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Missoula, Montana, United States
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Lincoln, Nebraska, United States
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Highland Park, New Jersey, United States
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Marlton, New Jersey, United States
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Northfield, New Jersey, United States
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Piscataway, New Jersey, United States
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Toms River, New Jersey, United States
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Verona, New Jersey, United States
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Albuquerque, New Mexico, United States
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New Hyde Park, New York, United States
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New York, New York, United States
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Rochester, New York, United States
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Staten Island, New York, United States
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Staten Island, New York, United States
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The Bronx, New York, United States
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Charlotte, North Carolina, United States
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Elizabeth City, North Carolina, United States
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Gastonia, North Carolina, United States
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Greenville, North Carolina, United States
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High Point, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Cincinnati, Ohio, United States
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Cincinnati, Ohio, United States
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Grove City, Ohio, United States
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Edmond, Oklahoma, United States
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Tulsa, Oklahoma, United States
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Clackamas, Oregon, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Reading, Pennsylvania, United States
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Anderson, South Carolina, United States
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Gaffney, South Carolina, United States
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Greenville, South Carolina, United States
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Greenville, South Carolina, United States
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North Charleston, South Carolina, United States
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Rock Hill, South Carolina, United States
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Sioux Falls, South Dakota, United States
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Franklin, Tennessee, United States
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Cypress, Texas, United States
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Dallas, Texas, United States
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Dallas, Texas, United States
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Fort Worth, Texas, United States
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Galveston, Texas, United States
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McKinney, Texas, United States
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San Antonio, Texas, United States
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San Antonio, Texas, United States
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San Antonio, Texas, United States
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Provo, Utah, United States
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South Burlington, Vermont, United States
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Abingdon, Virginia, United States
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Fairfax, Virginia, United States
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North Chesterfield, Virginia, United States
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Williamsburg, Virginia, United States
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Everett, Washington, United States
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Spokane, Washington, United States
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Tacoma, Washington, United States
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Madison, Wisconsin, United States
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Milwaukee, Wisconsin, United States
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Milwaukee, Wisconsin, United States
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West Allis, Wisconsin, United States
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Feldbach, , Austria
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Vienna, , Austria
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Liège, , Belgium
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Montigny-le-Tilleul, , Belgium
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Namur, , Belgium
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Calgary, Alberta, Canada
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Kelowna, British Columbia, Canada
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Vancouver, British Columbia, Canada
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Vancouver, British Columbia, Canada
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Winnipeg, Manitoba, Canada
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Ajax, Ontario, Canada
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Burlington, Ontario, Canada
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Mississauga, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Aarhus N, , Denmark
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Odense C, , Denmark
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Vejle, , Denmark
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Helsinki, , Finland
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Turku, , Finland
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Bayonne, , France
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Besançon, , France
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Brest, , France
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Dijon, , France
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Grenoble, , France
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La Roche-sur-Yon, , France
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Le Kremlin-Bicêtre, , France
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Lille, , France
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Lyon, , France
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Marseille, , France
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Montpellier, , France
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Nantes, , France
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Nice, , France
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Paris, , France
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Pessac, , France
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Reims, , France
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Rouen, , France
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Saint-Quentin, , France
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Strasbourg, , France
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Toulouse, , France
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Vandœuvre-lès-Nancy, , France
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Berlin, , Germany
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Bochum, , Germany
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Bonn, , Germany
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Cottbus, , Germany
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Essen, , Germany
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Hamburg, , Germany
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Jena, , Germany
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Marburg, , Germany
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Oldenburg, , Germany
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Regensburg, , Germany
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Rheine, , Germany
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Rüdersdorf, , Germany
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Wangen, , Germany
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Brescia, , Italy
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Catania, , Italy
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Catanzaro, , Italy
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Cona, , Italy
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Foggia, , Italy
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Garbagnate Milanese, , Italy
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Legnago, , Italy
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Matera, , Italy
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Milan, , Italy
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Milan, , Italy
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Modena, , Italy
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Napoli, , Italy
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Padua, , Italy
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Palermo, , Italy
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Pavia, , Italy
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Piacenza, , Italy
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Pietra Ligure, , Italy
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Reggio Emilia, , Italy
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Roma, , Italy
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Rozzano, , Italy
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Verona, , Italy
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Amersfoort, , Netherlands
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Deventer, , Netherlands
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Enschede, , Netherlands
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Harderwijk, , Netherlands
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Helmond, , Netherlands
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Nijmegen, , Netherlands
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Zwolle, , Netherlands
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Bergen, , Norway
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Lørenskog, , Norway
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Badalona(Barcelona), , Spain
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Barcelona, , Spain
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Barcelona, , Spain
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Benalmádena, , Spain
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Jerez de la Frontera, , Spain
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Laredo, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Málaga, , Spain
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Palma de Mallorca, , Spain
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Pozuelo de Alarcón, , Spain
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Sabadell, , Spain
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Salamanca, , Spain
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Santiago de Compostela, , Spain
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Seville, , Spain
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Taco, , Spain
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Valdemoro, , Spain
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Lund, , Sweden
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Östersund, , Sweden
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Stockholm, , Sweden
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Birmingham, , United Kingdom
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Bradford, , United Kingdom
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Cambridge, , United Kingdom
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Chertsey, , United Kingdom
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Dundee, , United Kingdom
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Glasgow, , United Kingdom
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London, , United Kingdom
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Nottingham, , United Kingdom
Countries
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References
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Louis R, Harrison TW, Chanez P, Menzella F, Philteos G, Cosio BG, Lugogo NL, de Luiz G, Burden A, Adlington T, Keeling N, Kwiatek J, Garcia Gil E; ANDHI Study Investigators. Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy. J Allergy Clin Immunol Pract. 2023 Jun;11(6):1759-1770.e7. doi: 10.1016/j.jaip.2023.03.009. Epub 2023 Mar 21.
Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.
Harrison TW, Chanez P, Menzella F, Canonica GW, Louis R, Cosio BG, Lugogo NL, Mohan A, Burden A, McDermott L, Garcia Gil E, Zangrilli JG; ANDHI study investigators. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial. Lancet Respir Med. 2021 Mar;9(3):260-274. doi: 10.1016/S2213-2600(20)30414-8. Epub 2020 Dec 22.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Other Identifiers
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2017-001040-35
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D3250C00045
Identifier Type: -
Identifier Source: org_study_id