AzTrials
AzTrials

AsthmaPhase 3ANDHINCT03170271

A Study of the Safety and Effectiveness of Benralizumab to Treat Patients With Severe Uncontrolled Asthma.

A Phase 3 study testing Benralizumab (Medi-563) in people with Asthma, run by AstraZeneca at 213 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Asthma
What is being tested?
Benralizumab (Medi-563)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
660 participants
Where
213 sitesin 14 countries
Study dates
7 Jul 2017to 21 Oct 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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:
  • 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:
  • 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
  • History of nasal polyposis
  • Age of asthma onset ≥18 years
  • Three or more documented exacerbations requiring systemic corticosteroid treatment during the 12 months prior to screening
  • 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:
  • Patients study must have completed ANDHI EOT Visit 11.
  • Written informed consent must also be obtained prior to any study related procedures being performed in the open label ANDHI IP sub study.
  • 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.

Who cannot join

  • 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.
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  • 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 should not enter the open label ANDHI IP sub study if any of the following exclusion criteria are fulfilled. Each exclusion criterion should be reviewed in all potential participants, including those who transition directly from the double-blind period and those with a delay between completing the EOT Visit 11 and the first open label visit (Visit 13).
  • 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.
  • 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.
  • Planned surgical procedures during the conduct of the study.
  • Positive urine pregnancy test at Visit 13, or currently breastfeeding or lactating women.

Trial locations and contacts

213 sites in 14 countries.

213 sites in 14 countries

United States100 sites

  • Research Site

    Abingdon, Virginia, 24210

  • Research Site

    Albany, Georgia, 31707

  • Research Site

    Albuquerque, New Mexico, 87106

  • Research Site

    Anderson, South Carolina, 29621

  • Research Site

    Ann Arbor, Michigan, 48109

  • Research Site

    Aurora, Colorado, 80045

  • Research Site

    Bakersfield, California, 93301

  • Research Site

    Birmingham, Alabama, 35209

  • Research Site

    Charlotte, North Carolina, 28277

  • Research Site

    Chevy Chase, Maryland, 20815

  • Research Site

    Cincinnati, Ohio, 45231

  • Research Site

    Cincinnati, Ohio, 45242

  • Research Site

    Clackamas, Oregon, 97015-5737

  • Research Site

    Clearwater, Florida, 33765

  • Research Site

    Cypress, Texas, 77429

  • Research Site

    Dallas, Texas, 75225

  • Research Site

    Dallas, Texas, 75246

  • Research Site

    Edmond, Oklahoma, 73034

  • Research Site

    Elizabeth City, North Carolina, 27909

  • Research Site

    Encinitas, California, 92024

  • Research Site

    Everett, Washington, 98208

  • Research Site

    Fairfax, Virginia, 22030

  • Research Site

    Fort Worth, Texas, 76109

  • Research Site

    Franklin, Tennessee, 37067

  • Research Site

    Gaffney, South Carolina, 29340

  • Research Site

    Galveston, Texas, 77555

  • Research Site

    Gastonia, North Carolina, 28054

  • Research Site

    Greenville, North Carolina, 27834

  • Research Site

    Greenville, South Carolina, 29607

  • Research Site

    Greenville, South Carolina, 29615

  • Research Site

    Grove City, Ohio, 43123

  • Research Site

    High Point, North Carolina, 27262

  • Research Site

    Highland Park, New Jersey, 08904

  • Research Site

    Iowa City, Iowa, 52242

  • Research Site

    Jacksonville, Florida, 32099

  • Research Site

    Kissimmee, Florida, 34741

  • Research Site

    Lakeside Park, Kentucky, 41017

  • Research Site

    Lincoln, Nebraska, 68510

  • Research Site

    Little Rock, Arkansas, 72209

  • Research Site

    Long Beach, California, 90806

  • Research Site

    Los Angeles, California, 90025

  • Research Site

    Madison, Wisconsin, 53792

  • Research Site

    Marlton, New Jersey, 08053

  • Research Site

    McKinney, Texas, 75069

  • Research Site

    Miami, Florida, 33126

  • Research Site

    Miami, Florida, 33173

  • Research Site

    Milwaukee, Wisconsin, 53226

  • Research Site

    Milwaukee, Wisconsin, 53228

  • Research Site

    Minneapolis, Minnesota, 55402

  • Research Site

    Mission Viejo, California, 92691

  • Research Site

    Missoula, Montana, 59808

  • Research Site

    New Haven, Connecticut, 06519

  • Research Site

    New Hyde Park, New York, 11042

  • Research Site

    New York, New York, 10016

  • Research Site

    Newport Beach, California, 92663

  • Research Site

    North Charleston, South Carolina, 29420-4211

  • Research Site

    North Chesterfield, Virginia, 23225

  • Research Site

    North Dartmouth, Massachusetts, 02747

  • Research Site

    Northfield, New Jersey, 08225

  • Research Site

    Owensboro, Kentucky, 42301

  • Research Site

    Peoria, Illinois, 61602

  • Research Site

    Philadelphia, Pennsylvania, 19107

  • Research Site

    Piscataway, New Jersey, 08854

  • Research Site

    Pittsburgh, Pennsylvania, 15213

  • Research Site

    Pittsburgh, Pennsylvania, 15241

  • Research Site

    Provo, Utah, 84604

  • Research Site

    Reading, Pennsylvania, 19610

  • Research Site

    Riverside, California, 92506

  • Research Site

    Rochester, New York, 14618

  • Research Site

    Rock Hill, South Carolina, 29732

  • Research Site

    San Antonio, Texas, 78229

  • Research Site

    San Antonio, Texas, 78249

  • Research Site

    San Antonio, Texas, 78251

  • Research Site

    San Diego, California, 92108

  • Research Site

    Savannah, Georgia, 31406

  • Research Site

    Shreveport, Louisiana, 71106

  • Research Site

    Sioux Falls, South Dakota, 57108

  • Research Site

    South Bend, Indiana, 46617

  • Research Site

    South Burlington, Vermont, 05403

  • Research Site

    Spokane, Washington, 99204

  • Research Site

    St Louis, Missouri, 63156

  • Research Site

    Staten Island, New York, 10305

  • Research Site

    Staten Island, New York, 10310

  • Research Site

    Stockton, California, 95207

  • Research Site

    Tacoma, Washington, 98405

  • Research Site

    The Bronx, New York, 10459

  • Research Site

    Toms River, New Jersey, 08755

  • Research Site

    Tucson, Arizona, 85724

  • Research Site

    Tulsa, Oklahoma, 74136

  • Research Site

    Verona, New Jersey, 07044

  • Research Site

    Walnut Creek, California, 94598

  • Research Site

    Waterbury, Connecticut, 06708

  • Research Site

    West Allis, Wisconsin, 53227

  • Research Site

    West Des Moines, Iowa, 50266

  • Research Site

    White Marsh, Maryland, 21162

  • Research Site

    Williamsburg, Virginia, 23188

  • Research Site

    Winston-Salem, North Carolina, 27103

  • Research Site

    Winston-Salem, North Carolina, 27157

  • Research Site

    Winter Park, Florida, 32789

  • Research Site

    Ypsilanti, Michigan, 48197

Other trials in United States

France21 sites

  • Research Site

    Bayonne, 64100

  • Research Site

    Besançon, 25030

  • Research Site

    Brest, 29609

  • Research Site

    Dijon, 21079

  • Research Site

    Grenoble, 38043

  • Research Site

    La Roche-sur-Yon, 85925

  • Research Site

    Le Kremlin-Bicêtre, 94270

  • Research Site

    Lille, 59037

  • Research Site

    Lyon, 69317

  • Research Site

    Marseille, 13015

  • Research Site

    Montpellier, 34090

  • Research Site

    Nantes, 44093

  • Research Site

    Nice, 06002

  • Research Site

    Paris, 75877

  • Research Site

    Pessac, 33604

  • Research Site

    Reims, 51092

  • Research Site

    Rouen, 76031

  • Research Site

    Saint-Quentin, 02321

  • Research Site

    Strasbourg, 67091

  • Research Site

    Toulouse, 31059

  • Research Site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Italy21 sites

  • Research Site

    Brescia, 25123

  • Research Site

    Catania, 95123

  • Research Site

    Catanzaro, 88100

  • Research Site

    Cona, 44124

  • Research Site

    Foggia, 71100

  • Research Site

    Garbagnate Milanese, 20024

  • Research Site

    Legnago, 37045

  • Research Site

    Matera

  • Research Site

    Milan, 20157

  • Research Site

    Milan, 20122

  • Research Site

    Modena, 41124

  • Research Site

    Naples, 80131

  • Research Site

    Padova, 35128

  • Research Site

    Palermo, 90127

  • Research Site

    Pavia, 27100

  • Research Site

    Piacenza, 29100

  • Research Site

    Pietra Ligure, 17027

  • Research Site

    Reggio Emilia, 42123

  • Research Site

    Roma, 00168

  • Research Site

    Rozzano, 20089

  • Research Site

    Verona, 37126

Other trials in Italy

Spain17 sites

  • Research Site

    Badalona(Barcelona), 08916

  • Research Site

    Barcelona, 08035

  • Research Site

    Barcelona, 08036

  • Research Site

    Benalmádena, 29631

  • Research Site

    Jerez de la Frontera, 11407

  • Research Site

    Laredo, 39770

  • Research Site

    Madrid, 28031

  • Research Site

    Madrid, 28034

  • Research Site

    Málaga, 29730

  • Research Site

    Palma de Mallorca, 07010

  • Research Site

    Pozuelo de Alarcón, 28223

  • Research Site

    Sabadell, 08208

  • Research Site

    Salamanca, 37007

  • Research Site

    Santiago de Compostela, 15706

  • Research Site

    Seville, 41009

  • Research Site

    Taco, 38108

  • Research Site

    Valdemoro, 28342

Other trials in Spain

Germany13 sites

  • Research Site

    Berlin, 14059

  • Research Site

    Bochum, 44789

  • Research Site

    Bonn, 53105

  • Research Site

    Cottbus, 03050

  • Research Site

    Essen, 45239

  • Research Site

    Hamburg, 20354

  • Research Site

    Jena, 07747

  • Research Site

    Marburg, 30625

  • Research Site

    Oldenburg, 23758

  • Research Site

    Regensburg, 93053

  • Research Site

    Rheine, 48431

  • Research Site

    Rüdersdorf, 15562

  • Research Site

    Wangen, 88239

Other trials in Germany

Canada11 sites

  • Research Site

    Ajax, Ontario, L1S 2J5

  • Research Site

    Burlington, Ontario, L7N 3V2

  • Research Site

    Calgary, Alberta, T2N 4Z6

  • Research Site

    Kelowna, British Columbia, V1W 1V3

  • Research Site

    Mississauga, Ontario, L5A 3V4

  • Research Site

    Montreal, Quebec, H4A 3J1

  • Research Site

    Québec, Quebec, G1V 4W2

  • Research Site

    Toronto, Ontario, M5T 3A9

  • Research Site

    Vancouver, British Columbia, V5Z 1M9

  • Research Site

    Vancouver, British Columbia, V6Z 1Y6

  • Research Site

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

United Kingdom8 sites

  • Research Site

    Birmingham, B9 5SS

  • Research Site

    Bradford, BND9 6RJ

  • Research Site

    Cambridge, CB2 2QQ

  • Research Site

    Chertsey, KT16 0PZ

  • Research Site

    Dundee, DD1 9SY

  • Research Site

    Glasgow, G51 4TF

  • Research Site

    London, EC1A 7BE

  • Research Site

    Nottingham, NG5 1PB

Other trials in United Kingdom

Netherlands7 sites

  • Research Site

    Amersfoort, 3813 TZ

  • Research Site

    Deventer, 7416 SE

  • Research Site

    Enschede, 7513 ER

  • Research Site

    Harderwijk, 3844 DG

  • Research Site

    Helmond, 5707 HA

  • Research Site

    Nijmegen, 6532 SZ

  • Research Site

    Zwolle, 8025 AB

Other trials in Netherlands

Belgium3 sites

  • Research Site

    Liège, 4000

  • Research Site

    Montigny-le-Tilleul, 6110

  • Research Site

    Namur, 5101

Other trials in Belgium

Denmark3 sites

  • Research Site

    Aarhus N, 8200

  • Research Site

    Odense C, 5000

  • Research Site

    Vejle, 7100

Other trials in Denmark

Sweden3 sites

  • Research Site

    Lund, 221 85

  • Research Site

    Östersund, 831 83

  • Research Site

    Stockholm, SE-181 58

Other trials in Sweden

Austria2 sites

  • Research Site

    Feldbach, A-8330

  • Research Site

    Vienna, 1130

Other trials in Austria

Finland2 sites

  • Research Site

    Helsinki, 00290

  • Research Site

    Turku, 20520

Other trials in Finland

Norway2 sites

  • Research Site

    Bergen, 5021

  • Research Site

    Lørenskog, N-1478

Other trials in Norway

About this study

Official title: 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

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.

Read the detailed description

This is a Phase IIIb, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and the safety of repeat dosing of benralizumab 30 mg subcutaneous (sc) versus placebo on top of standard of care asthma therapy in patients with severe uncontrolled asthma. Approximately 630 patients with peripheral blood eosinophil counts ≥150 cells/μL will be randomized 2:1 to receive benralizumab 30 mg sc or matched placebo for 24 weeks.

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
Asthma
Being tested
Benralizumab (Medi-563), Placebo
Keywords
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases, Additional relevant MeSH terms:, Asthma, Inflammation, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases Respiratory Hypersensitivity, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases, Pathologic Processes
Medical subject headings
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Lung Diseases, Obstructive, Inflammation, Hypersensitivity, Immediate, Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Benralizumab (Medi-563)Drug

    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).

  • PlaceboDrug

    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)

Study groups in NCT03170271
Study groupRoleWhat they receive
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).
Receives: Drug: Benralizumab (Medi-563)
PlaceboPlacebo 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)
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (Week 0) up to Week 24

Secondary outcomes (10)

  1. Change From Baseline in Saint George Respiratory Questionnaire (SGRQ) Total Score to the EOT (Week 24)

    The SGRQ is a 50-item patient-reported outcome instrument which measures the health status of patients with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ total score indicates the impact of disease on overall health status and is expressed as a percentage of overall impairment (scores range from 0 to100, with 100 representing worst possible health status and 0 indicating the best possible health status). The least squares (LS) mean change from baseline in SGRQ total score at Week 24 is presented.

    Measured: Baseline (Week 0) and Week 24

  2. Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in First Second (FEV1) to the EOT (Week 24)

    Lung function was assessed by FEV1 which was measured by spirometry. Spirometry was performed by the Investigator or authorized delegate according to American Thoracic Society/European Respiratory Society guidelines. The LS mean change from baseline in pre-BD FEV1 at Week 24 is presented.

    Measured: Baseline (Week 0) and Week 24

  3. Change From Baseline in Asthma Control Questionnaire 6 (ACQ-6) Score to the EOT (Week 24)

    The ACQ-6 is a shortened version of the ACQ that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath and wheezing) and short-acting β-2 receptor agonist use. Patients were asked to recall the status of their asthma during the previous week and respond to the questions of the ACQ-6 on a 7-point scale. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is computed as the mean of the responses from all the items in the questionnaire. Mean scores of ≤0.75 indicated well-controlled asthma, scores between 0.75 and <1.5 indicated partly-controlled asthma, and a score ≥1.5 indicated not well-controlled asthma. The LS mean change from baseline in ACQ-6 score at Week 24 is presented.

    Measured: Baseline (Week 0) and Week 24

  4. Time to First Asthma Exacerbation (up to Week 24)

    Time to first asthma exacerbation was derived as follows:

    Start date of first asthma exacerbation - Date of randomization + 1. The time to first asthma exacerbation for patients who did not experience an asthma exacerbation during the treatment period was censored at the EOT visit (Week 24) for patients who completed the study. Patients who withdrew from the study or were lost to follow-up before the EOT visit were censored at the last visit date after which an exacerbation could not be assessed. The median time to first asthma exacerbation was not calculated, so the number of patients who experienced an asthma exacerbation is presented for the measured values.

    Measured: Baseline (Week 0) up to Week 24

  5. Change From Run-in Baseline Home Peak Expiratory Flow (PEF) (Morning and Evening) to the EOT (Week 24)

    Home PEF testing was performed by the patient each morning after awakening and before taking their morning asthma medications, and each evening using a peak flow meter. Measurements were taken at approximately the same time each day and recorded in the Asthma Daily Diary. The maximum of the 3 measurements performed every morning and evening were used in the calculation of the weekly means. A weekly mean was calculated as the sum of all non-missing daily measures over the 7 sequential days divided by the number of non-missing daily measures. If more than 3 daily measures (> 50%) within a period were missing, then the weekly mean for that period was set to 'missing'. Change from run-in baseline in weekly means for morning PEF and evening PEF are presented. Baseline was the average for data collected over the last 7 days of the run-in period prior to randomization.

    Measured: Run-in baseline (from Day -28 to Day 0) and Week 24

  6. Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24)

    The SF-36v2 is a 36-item survey of functional health and well-being, with a 1 week recall period. The 8-domain profile consists of the following subscales: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The physical and mental health component summary scores are computed from subscale scores to give a broader metric of physical and mental health-related quality of life. Each domain score, as well as the physical and mental component scores, were scored on a scale from 0-100 (worst health possible to best health possible); higher scores indicate better health status. Norm-based scoring was used to calculate the 8 SF-36v2 subscales and the 2 component scores. The LS mean change from baseline in each of the SF-36 subscale and component summary scores at Week 24 are presented.

    Measured: Baseline (Week 0) and Week 24

  7. Patient Global Impression of Severity (PGI-S): Responder Status at the EOT (Week 24)

    The PGI-S is a single question asking the patient to rate the overall severity of their symptoms using a 6-point categorical response scale from 0 to 5 where 0=no symptoms and 5=very severe symptoms. Higher scores indicate a worse outcome. Improvement was defined as a PGI-S at EOT (Week 24) better than PGI-S at baseline. Important improvement was defined as PGI-S at baseline = moderate symptoms or severe symptoms or very severe symptoms shifting to PGI-S at EOT = no symptoms or very mild symptoms or mild symptoms. Patients with missing data at the EOT visit who did not complete the study were considered non-responders. For patients who completed the study with missing data at EOT (Week 24), their last evaluable post-baseline score was used to define responder status. The percentage of patients for each of the indicated PGI-S responder categories are presented.

    Measured: Baseline (Week 0) and Week 24

  8. Clinician Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C): Responder Status at the EOT (Week 24)

    The Investigator (clinician) and the patient were asked separately to rate the degree of change in the overall asthma status compared to the start of treatment, i.e. baseline randomization visit. A 7-point rating scale was used for the CGI-C (rated by Investigator) and PGI-C (rated by patient) where: 1=Very Much Improved; 2=Much Improved; 3=Minimally Improved; 4=No Changes; 5=Minimally Worse; 6=Much Worse, and 7=Very Much Worse. Higher scores indicate a worse outcome. Responder category definitions: Much improved = (Much improved, Very much improved); Very much improved = (Very much improved). Patients with missing data at the EOT visit who did not complete the study were considered non-responders. For patients who completed the study with missing data at EOT (Week 24), their last evaluable post-baseline score was used to define responder status. The percentage of patients for each of the indicated CGI-C and PGI-C responder categories are presented.

    Measured: Baseline (Week 0) and Week 24

  9. Change From Baseline in Predominant Symptom and Impairment Assessment (PSIA) Severity Score for Average of Top 3 Ranked Symptoms/Impairments and for Top Ranked Symptom/Impairment at the EOT (Week 24)

    For part 1 of the PSIA only administered at baseline, patients reviewed 8 concepts (including cardinal asthma symptoms, activities, awakenings, triggers) and selected those which were typically bothersome. Based on part 1 selections, part 2 of the PSIA produced a rank ordered list of bothersome concepts individualized per the patient for subsequent evaluation. For part 3 of the PSIA assessed at baseline and during the study, patients recorded the severity of each selected symptom or impairment using an 11-point numeric rating scale where: 0=Did not experience and 10=Worst I can imagine. Higher scores indicate a worse outcome. The LS mean change from baseline in PSIA severity score for the indicated categories at Week 24 are presented. A negative change from baseline indicates an improvement in symptoms. Note: Average PSIA was calculated only where all of top 3 ranked symptoms/impairments were available, otherwise average was set to missing.

    Measured: Baseline (Week 0) and Week 24

  10. Change From Baseline in the Sino-Nasal Outcome Test Item 22 (SNOT-22) Total Score to the EOT (Week 24)

    The 22-item SNOT 22 questionnaire was used to assess the rhinosinusitis health status and quality of life of patients with baseline chronic rhinosinusitis with nasal polyposis. The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110. Higher scores indicate poorer outcomes. The LS mean changes from baseline in SNOT-22 total score in patients in the chronic rhinosinusitis with nasal polyposis sub-study analysis set at Week 24 are presented.

    Measured: Baseline (Week 0) and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2017
  2. Study start7 Jul 2017
  3. Primary completion25 Sep 2019
  4. Study completion21 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
660 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03170271
Sponsor's protocol ID
D3250C00045
Other IDs
2017-001040-35, 2017
Acronym
ANDHI
Status last verified
Oct 2021
First submitted
26 May 2017
Last updated
1 Nov 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • 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.

    PubMed 36948488

  • 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.

    PubMed 33710614

  • 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.

    PubMed 33357499

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Benralizumab (Medi-563) in people with Asthma, run by AstraZeneca at 213 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 213 sites in United States, France, Italy, Spain, Germany and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annualized Rate of Asthma Exacerbations Over the Treatment Period (up to Week 24) (time frame: Baseline (Week 0) up to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03170271, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.

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