A Study of the Safety and Effectiveness of Benralizumab to Treat Patients With Severe Uncontrolled Asthma.
ANDHI
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo Controlled, Phase 3b Study to Evaluate the Safety and Efficacy of Benralizumab 30 mg sc in Patients With Severe Asthma Uncontrolled on Standard of Care Treatment
2 other identifiers
interventional
660
14 countries
213
Brief Summary
The purpose of this study is to investigate the effect of benralizumab on the rate of asthma exacerbations, patient reported quality of life and lung function during the 24-week treatment in patients with uncontrolled, severe asthma with an eosinophilic phenotype. A subset of patients will be assessed for their ongoing chronic rhinosinusitis with nasal polyps. The study design has been updated to include a 56-week open label ANDHI in Practice (ANDHI IP) sub study upon the completion of the 24-week double-blind period of the ANDHI study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 asthma
Started Jul 2017
Longer than P75 for phase_3 asthma
213 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2017
CompletedFirst Posted
Study publicly available on registry
May 31, 2017
CompletedStudy Start
First participant enrolled
July 7, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 25, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
October 21, 2020
CompletedResults Posted
Study results publicly available
December 16, 2020
CompletedNovember 1, 2021
October 1, 2021
2.2 years
May 26, 2017
September 24, 2020
October 20, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Annualized Rate of Asthma Exacerbations Over the Treatment Period (up to Week 24)
An asthma exacerbation was defined as a worsening of asthma that led to any of the following: * Use of systemic corticosteroids (or temporary increase in stable oral corticosteroids \[OCS\] background dose) for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. * An emergency room/urgent care visit (defined as evaluation and treatment for \< 24 hours in an emergency department or urgent care center) due to asthma that required systemic corticosteroids (as per above). * An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours) due to asthma. Annual exacerbation rate = 365.25\*total number of exacerbations / total duration of follow-up within the treatment group. Annual asthma exacerbation rates over the 24-week period were estimated using a negative binomial model.
Baseline (Week 0) up to Week 24
Secondary Outcomes (10)
Change From Baseline in Saint George Respiratory Questionnaire (SGRQ) Total Score to the EOT (Week 24)
Baseline (Week 0) and Week 24
Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in First Second (FEV1) to the EOT (Week 24)
Baseline (Week 0) and Week 24
Change From Baseline in Asthma Control Questionnaire 6 (ACQ-6) Score to the EOT (Week 24)
Baseline (Week 0) and Week 24
Time to First Asthma Exacerbation (up to Week 24)
Baseline (Week 0) up to Week 24
Change From Run-in Baseline Home Peak Expiratory Flow (PEF) (Morning and Evening) to the EOT (Week 24)
Run-in baseline (from Day -28 to Day 0) and Week 24
- +5 more secondary outcomes
Study Arms (2)
Benralizumab (Medi-563)
EXPERIMENTALBenralizumab (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).
Placebo
PLACEBO COMPARATORAdministered 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)
Interventions
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 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
You may qualify if:
- Female and male patients aged 18 to 75 years inclusively at the time of Visit 1 with a history of physician-diagnosed asthma requiring treatment with medium-to-high dose Inhaled Corticosteroids (ICS) plus asthma controller, for at least 12 months prior to Visit 1.
- 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.
- 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.
- ACQ6 score ≥1.5 at Visit 1.
- Screening pre-bronchodilator (pre-BD) FEV1 of \<80% predicted at Visit 2.
- Excessive variability in lung function by satisfying ≥ 1 of the following criteria:
- Airway reversibility (FEV1 ≥12%) using a short-acting bronchodilator demonstrated at Visit 2 or Visit 3.
- Airway reversibility to short-acting bronchodilator (FEV1 ≥12%) documented during the 12 months prior to enrolment Visit 1.
- Daily diurnal peak flow variability of \>10% when averaged over 7 continuous days during the study run-in period
- 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.
- 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.
- Peripheral blood eosinophil count either:
- cells/μL assessed by central laboratory at either Visit 1 or Visit 2
- ≥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:
- 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
- +6 more criteria
You may not qualify if:
- Clinically important pulmonary disease other than asthma
- Acute upper or lower respiratory infections within 30 days prior to the date informed consent.
- 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.
- History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
- A history of known immunodeficiency disorder.
- Current smokers or former smokers with a smoking history of ≥10 pack years.
- Previously received benralizumab (MEDI-563).
- Receipt of any investigational medication as part of a research study within approximately 5 half-lives prior to randomization.
- Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
- Receipt of live attenuated vaccines 30 days prior to the date of randomization; other types of vaccines are allowed.
- Concurrent enrolment in another interventional or post-authorization safety study
- 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.
- 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.
- 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.
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (213)
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Birmingham, Alabama, 35209, United States
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Tucson, Arizona, 85724, United States
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Little Rock, Arkansas, 72209, United States
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Bakersfield, California, 93301, United States
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Encinitas, California, 92024, United States
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Long Beach, California, 90806, United States
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Los Angeles, California, 90025, United States
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Mission Viejo, California, 92691, United States
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Newport Beach, California, 92663, United States
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Riverside, California, 92506, United States
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San Diego, California, 92108, United States
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Stockton, California, 95207, United States
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Walnut Creek, California, 94598, United States
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Aurora, Colorado, 80045, United States
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New Haven, Connecticut, 06519, United States
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Waterbury, Connecticut, 06708, United States
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Clearwater, Florida, 33765, United States
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Jacksonville, Florida, 32099, United States
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Kissimmee, Florida, 34741, United States
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Miami, Florida, 33126, United States
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Miami, Florida, 33173, United States
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Winter Park, Florida, 32789, United States
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Albany, Georgia, 31707, United States
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Savannah, Georgia, 31406, United States
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Peoria, Illinois, 61602, United States
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South Bend, Indiana, 46617, United States
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Iowa City, Iowa, 52242, United States
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West Des Moines, Iowa, 50266, United States
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Lakeside Park, Kentucky, 41017, United States
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Owensboro, Kentucky, 42301, United States
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Shreveport, Louisiana, 71106, United States
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Chevy Chase, Maryland, 20815, United States
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White Marsh, Maryland, 21162, United States
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North Dartmouth, Massachusetts, 02747, United States
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Ann Arbor, Michigan, 48109, United States
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Ypsilanti, Michigan, 48197, United States
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Minneapolis, Minnesota, 55402, United States
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St Louis, Missouri, 63156, United States
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Missoula, Montana, 59808, United States
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Lincoln, Nebraska, 68510, United States
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Highland Park, New Jersey, 08904, United States
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Marlton, New Jersey, 08053, United States
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Northfield, New Jersey, 08225, United States
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Piscataway, New Jersey, 08854, United States
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Toms River, New Jersey, 08755, United States
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Verona, New Jersey, 07044, United States
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Albuquerque, New Mexico, 87106, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10016, United States
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Rochester, New York, 14618, United States
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Staten Island, New York, 10305, United States
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Staten Island, New York, 10310, United States
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The Bronx, New York, 10459, United States
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Charlotte, North Carolina, 28277, United States
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Elizabeth City, North Carolina, 27909, United States
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Gastonia, North Carolina, 28054, United States
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Greenville, North Carolina, 27834, United States
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High Point, North Carolina, 27262, United States
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Winston-Salem, North Carolina, 27103, United States
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Winston-Salem, North Carolina, 27157, United States
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Cincinnati, Ohio, 45231, United States
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Cincinnati, Ohio, 45242, United States
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Grove City, Ohio, 43123, United States
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Edmond, Oklahoma, 73034, United States
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Tulsa, Oklahoma, 74136, United States
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Clackamas, Oregon, 97015-5737, United States
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Philadelphia, Pennsylvania, 19107, United States
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Pittsburgh, Pennsylvania, 15213, United States
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Pittsburgh, Pennsylvania, 15241, United States
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Reading, Pennsylvania, 19610, United States
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Anderson, South Carolina, 29621, United States
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Gaffney, South Carolina, 29340, United States
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Greenville, South Carolina, 29607, United States
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Greenville, South Carolina, 29615, United States
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North Charleston, South Carolina, 29420-4211, United States
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Rock Hill, South Carolina, 29732, United States
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Sioux Falls, South Dakota, 57108, United States
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Franklin, Tennessee, 37067, United States
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Cypress, Texas, 77429, United States
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Dallas, Texas, 75225, United States
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Dallas, Texas, 75246, United States
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Fort Worth, Texas, 76109, United States
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Galveston, Texas, 77555, United States
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McKinney, Texas, 75069, United States
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San Antonio, Texas, 78229, United States
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San Antonio, Texas, 78249, United States
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San Antonio, Texas, 78251, United States
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Provo, Utah, 84604, United States
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South Burlington, Vermont, 05403, United States
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Abingdon, Virginia, 24210, United States
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Fairfax, Virginia, 22030, United States
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North Chesterfield, Virginia, 23225, United States
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Williamsburg, Virginia, 23188, United States
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Everett, Washington, 98208, United States
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Spokane, Washington, 99204, United States
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Tacoma, Washington, 98405, United States
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Madison, Wisconsin, 53792, United States
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Milwaukee, Wisconsin, 53226, United States
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Milwaukee, Wisconsin, 53228, United States
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West Allis, Wisconsin, 53227, United States
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Feldbach, A-8330, Austria
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Vienna, 1130, Austria
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Liège, 4000, Belgium
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Montigny-le-Tilleul, 6110, Belgium
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Namur, 5101, Belgium
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Calgary, Alberta, T2N 4Z6, Canada
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Kelowna, British Columbia, V1W 1V3, Canada
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Vancouver, British Columbia, V5Z 1M9, Canada
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Vancouver, British Columbia, V6Z 1Y6, Canada
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Winnipeg, Manitoba, R2H 2A6, Canada
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Ajax, Ontario, L1S 2J5, Canada
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Burlington, Ontario, L7N 3V2, Canada
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Mississauga, Ontario, L5A 3V4, Canada
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Toronto, Ontario, M5T 3A9, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Québec, Quebec, G1V 4W2, Canada
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Aarhus N, 8200, Denmark
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Odense C, 5000, Denmark
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Vejle, 7100, Denmark
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Helsinki, 00290, Finland
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Turku, 20520, Finland
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Bayonne, 64100, France
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Besançon, 25030, France
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Brest, 29609, France
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Dijon, 21079, France
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Grenoble, 38043, France
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La Roche-sur-Yon, 85925, France
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Le Kremlin-Bicêtre, 94270, France
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Lille, 59037, France
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Lyon, 69317, France
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Marseille, 13015, France
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Montpellier, 34090, France
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Nantes, 44093, France
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Nice, 06002, France
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Paris, 75877, France
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Pessac, 33604, France
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Reims, 51092, France
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Rouen, 76031, France
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Saint-Quentin, 02321, France
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Strasbourg, 67091, France
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Toulouse, 31059, France
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Vandœuvre-lès-Nancy, 54511, France
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Berlin, 14059, Germany
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Bochum, 44789, Germany
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Bonn, 53105, Germany
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Cottbus, 03050, Germany
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Essen, 45239, Germany
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Hamburg, 20354, Germany
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Jena, 07747, Germany
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Marburg, 30625, Germany
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Oldenburg, 23758, Germany
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Regensburg, 93053, Germany
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Rheine, 48431, Germany
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Rüdersdorf, 15562, Germany
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Wangen, 88239, Germany
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Brescia, 25123, Italy
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Catania, 95123, Italy
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Catanzaro, 88100, Italy
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Cona, 44124, Italy
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Foggia, 71100, Italy
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Garbagnate Milanese, 20024, Italy
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Legnago, 37045, Italy
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Matera, Italy
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Milan, 20157, Italy
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Milan, 20122, Italy
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Modena, 41124, Italy
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Napoli, 80131, Italy
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Padua, 35128, Italy
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Palermo, 90127, Italy
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Pavia, 27100, Italy
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Piacenza, 29100, Italy
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Pietra Ligure, 17027, Italy
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Reggio Emilia, 42123, Italy
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Roma, 00168, Italy
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Rozzano, 20089, Italy
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Verona, 37126, Italy
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Amersfoort, 3813 TZ, Netherlands
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Deventer, 7416 SE, Netherlands
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Enschede, 7513 ER, Netherlands
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Harderwijk, 3844 DG, Netherlands
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Helmond, 5707 HA, Netherlands
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Nijmegen, 6532 SZ, Netherlands
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Zwolle, 8025 AB, Netherlands
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Bergen, 5021, Norway
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Lørenskog, N-1478, Norway
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Badalona(Barcelona), 08916, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Benalmádena, 29631, Spain
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Jerez de la Frontera, 11407, Spain
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Laredo, 39770, Spain
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Madrid, 28031, Spain
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Madrid, 28034, Spain
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Málaga, 29730, Spain
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Palma de Mallorca, 07010, Spain
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Pozuelo de Alarcón, 28223, Spain
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Sabadell, 08208, Spain
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Salamanca, 37007, Spain
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Santiago de Compostela, 15706, Spain
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Seville, 41009, Spain
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Taco, 38108, Spain
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Valdemoro, 28342, Spain
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Lund, 221 85, Sweden
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Östersund, 831 83, Sweden
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Stockholm, SE-181 58, Sweden
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Birmingham, B9 5SS, United Kingdom
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Bradford, BND9 6RJ, United Kingdom
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Cambridge, CB2 2QQ, United Kingdom
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Chertsey, KT16 0PZ, United Kingdom
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Dundee, DD1 9SY, United Kingdom
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Glasgow, G51 4TF, United Kingdom
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London, EC1A 7BE, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
Related Publications (3)
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.
PMID: 36948488DERIVEDChong 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.
PMID: 33710614DERIVEDHarrison 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.
PMID: 33357499DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Brad Goodman, MD
Aero Allergy Research Lab of Savannah
- PRINCIPAL INVESTIGATOR
Vinay Sikand, MD
Sikand Institute of Pulmonary Research
- PRINCIPAL INVESTIGATOR
Willaim Cherry, MD
Riverside Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 26, 2017
First Posted
May 31, 2017
Study Start
July 7, 2017
Primary Completion
September 25, 2019
Study Completion
October 21, 2020
Last Updated
November 1, 2021
Results First Posted
December 16, 2020
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will share