Efficacy and Safety Study of Benralizumab Added to High-dose Inhaled Corticosteroid Plus LABA in Patients With Uncontrolled Asthma

Asthma Clinical Trial

Official title:

A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III Efficacy and Safety Study of Benralizumab (MEDI-563) Added to High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist in Patients With Uncontrolled Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01928771
• Other study ID #: D3250C00017
• Status: Completed
• Phase: Phase 3
• First received: August 16, 2013
• Last updated: May 9, 2016
• Start date: September 2013
• Est. completion date: April 2016

Study information

• Verified date: May 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardBrazil: Ministry of HealthMexico: Ministry of HealthPeru: Ministry of HealthAustralia: Department of Health and Ageing Therapeutic Goods AdministrationSouth Korea: Korea Food and Drug Administration (KFDA)Bulgaria: Bulgarian Drug AgencyCzech Republic: State Institute for Drug ControlRussia: Ministry of Health of the Russian FederationSouth Africa: Medicines Control CouncilTurkey: Ministry of HealthFrance: National Agency for the Safety of Medicine and Health ProductsItaly: The Italian Medicines AgencySpain: Spanish Agency of Medicines and Health ProductsUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyPoland: Ministry of HealthVietnam: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether Benralizumab reduces the number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2700
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Written informed consent for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent[s]/guardian[s]) and according to international guidelines and/or applicable European Union guidelines.

2. Female and Male aged 12 to 75 years inclusively, at the time of visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial.

3. History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250µg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1

4. Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers.

• For subjects 18 years of age and older, the ICS dose must be >500 mcg/day fluticasone propionate dry powder formulation or equivalent daily.

• For subjects ages 12-17, the ICS dose must be =500 mcg /day fluticasone propionate dry powder formulation or equivalent daily.

Exclusion criteria:

1. Clinically important pulmonary disease other than asthma (e.g. active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome)

2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:

• Affect the safety of the patient throughout the study

• Influence the findings of the studies or their interpretations

• Impede the patient's ability to complete the entire duration of study

3. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period

4. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Benralizumab
Benralizumab subcutaneously on study week 0 until study week 44 inclusive.
• Placebo
Placebo subcutaneously on study week 0 until study week 44 inclusive.

Locations

Country	Name	City	State
Australia	Research Site	Bedford Park
Australia	Research Site	Box Hill
Australia	Research Site	Clayton
Australia	Research Site	Concord
Australia	Research Site	Frankston
Australia	Research Site	Nedlands
Australia	Research Site	New Lambton Heights
Australia	Research Site	Parkville
Australia	Research Site	Prahran
Australia	Research Site	Randwick
Australia	Research Site	Woolloongabba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo André
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Sorocaba
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Pernik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Samokov
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Velingrad
Bulgaria	Research Site	Yambol
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Jindrichuv Hradec
Czech Republic	Research Site	Karlovy Vary
Czech Republic	Research Site	Ostrava
Czech Republic	Research Site	Pardubice
Czech Republic	Research Site	Plzen
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Rokycany
Czech Republic	Research Site	Strakonice
Czech Republic	Research Site	Teplice
France	Research Site	Brest
France	Research Site	Clermont Ferrand
France	Research Site	Dijon Cedex
France	Research Site	Le Kremlin Bicêtre
France	Research Site	Le Mans Cedex
France	Research Site	Lyon Cedex 4
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Pau Cedex
France	Research Site	Pringy Cedex
France	Research Site	Saint Pierre
France	Research Site	Strasbourg Cedex
France	Research Site	Toulouse
Italy	Research Site	Bari
Italy	Research Site	Bologna
Italy	Research Site	Catania
Italy	Research Site	Cona
Italy	Research Site	Firenze
Italy	Research Site	Foggia
Italy	Research Site	Legnago
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Palermo
Italy	Research Site	Pavia
Italy	Research Site	Perugia
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	San Pietro Vernotico
Italy	Research Site	Torino
Italy	Research Site	Verona
Korea, Republic of	Research Site	Anyang-si
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jeju-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Mexico	Research Site	Guadalajara
Mexico	Research Site	Monterrey
Mexico	Research Site	Morelia
Peru	Research Site	Cusco
Peru	Research Site	Lima
Peru	Research Site	Surco
Poland	Research Site	Bialystok
Poland	Research Site	Dobre Miasto
Poland	Research Site	Gdansk
Poland	Research Site	Gizycko
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Koscian
Poland	Research Site	Legnica
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Proszowice
Poland	Research Site	Rzeszów
Poland	Research Site	Sosnowiec
Poland	Research Site	Wolomin
Poland	Research Site	Wroclaw
Poland	Research Site	Zgierz
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	Saint - Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	StPetersburg
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Vladimir
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Yaroslavl
Russian Federation	Research Site	Yekaterinburg
South Africa	Research Site	Benoni
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Mowbray
South Africa	Research Site	Stanger
Spain	Research Site	Barcelona
Spain	Research Site	Lugo
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Oviedo
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Sagunto(Valencia)
Spain	Research Site	Salamanca
Spain	Research Site	Valencia
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Kocaeli
Turkey	Research Site	Mersin
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Chertsey
United Kingdom	Research Site	Chester
United Kingdom	Research Site	Chippenham
United Kingdom	Research Site	Cottingham
United Kingdom	Research Site	Darlington
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	High Heaton/Newcastle upon Tyn
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	Maidstone
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Soham
United Kingdom	Research Site	Somerset
United Kingdom	Research Site	Stevenage
United Kingdom	Research Site	Stockton
United States	Research Site	Abingdon	Virginia
United States	Research Site	Albany	Georgia
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Allen	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Beverly Hills	California
United States	Research Site	Billings	Montana
United States	Research Site	Brandon	Florida
United States	Research Site	Bronx	New York
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Clearwater	Florida
United States	Research Site	Costa Mesa	California
United States	Research Site	Cutler Bay	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	DeLand	Florida
United States	Research Site	Dickinson	Texas
United States	Research Site	Duncanville	Texas
United States	Research Site	Easley	South Carolina
United States	Research Site	Erie	Pennsylvania
United States	Research Site	Feasterville	Pennsylvania
United States	Research Site	Foley	Alabama
United States	Research Site	Fort Mitchell	Kentucky
United States	Research Site	Gainesville	Georgia
United States	Research Site	Gainesville	Florida
United States	Research Site	Gardner	Massachusetts
United States	Research Site	Georgetown	Texas
United States	Research Site	Germantown	Tennessee
United States	Research Site	Grand Forks	North Dakota
United States	Research Site	Greenfield	Wisconsin
United States	Research Site	Gurnee	Illinois
United States	Research Site	Hartford	Connecticut
United States	Research Site	Hazard	Kentucky
United States	Research Site	Hialeah	Florida
United States	Research Site	Hodges	South Carolina
United States	Research Site	Hollywood	Florida
United States	Research Site	Homestead	Florida
United States	Research Site	Hopewell	Virginia
United States	Research Site	Hopewell Jct	New York
United States	Research Site	Houston	Texas
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntington Park	California
United States	Research Site	Huntsville	Alabama
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jackonsville	Florida
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Los Angles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Lynn Haven	Florida
United States	Research Site	Marlton	New Jersey
United States	Research Site	McAllen	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Mobile	Alabama
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Mt Pleasant	South Carolina
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York City	New York
United States	Research Site	Newport Beach	California
United States	Research Site	Normal	Illinois
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	Northfield	New Jersey
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Opelousas	Louisiana
United States	Research Site	Orange	California
United States	Research Site	Oregon	Ohio
United States	Research Site	Orem	Utah
United States	Research Site	Orlando	Florida
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Pharr	Texas
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenixville	Pennsylvania
United States	Research Site	Picayune	Mississippi
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Plano	Texas
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Port Huron	Michigan
United States	Research Site	Provo	Utah
United States	Research Site	Quincy	Massachusetts
United States	Research Site	Riverside	California
United States	Research Site	Rochester	Minnesota
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Jose	California
United States	Research Site	Santa Ana	California
United States	Research Site	Scottsboro	Alabama
United States	Research Site	Sealy	Texas
United States	Research Site	Sebring	Florida
United States	Research Site	Sheffield	Alabama
United States	Research Site	Shelby	North Carolina
United States	Research Site	Sparks	Nevada
United States	Research Site	Splendora	Texas
United States	Research Site	St Petersburg	Florida
United States	Research Site	St. Paul	Minnesota
United States	Research Site	Staten Island	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Toledo	Ohio
United States	Research Site	Tucson	Arizona
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Union	New Jersey
United States	Research Site	Vero Beach	Florida
United States	Research Site	Warwick	Rhode Island
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Wooster	Ohio
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Brazil,  Bulgaria,  Czech Republic,  France,  Italy,  Korea, Republic of,  Mexico,  Peru,  Poland,  Russian Federation,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of 2 dosing regimens of benralizumab on asthma exacerbations in adult patients with uncontrolled asthma	Annual asthma exacerbation rate	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on pulmonary function	Pre-dose/pre-bronchodilator FEV1 and post-bronchodilator FEV1 at the study centre	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics (per ePRO)	• Asthma symptom score (totals, day time, and night time) • Rescue medication use • Home lung function (morning and evening PEF) • Nights with awakening due to asthma • ACQ-6	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on emergency room visits/urgent care and hospitalizations due to asthma	Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the pharmacokinetics of benralizumab	PK parameters	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the safety and tolerability of 2 dosing regimens of benralizumab	- AE/SAE - Laboratory variables - ECG - Physical Examination	Immediately following the first administration of study drug through Study Week 48.	Yes
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on other parameters associated with asthma exacerbations	Time to first asthma exacerbation and proportion of patients with =1 asthma exacerbation	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the immunogenicity of benralizumab	- Anti-drug antibodies (ADA)	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on asthma related and general health-related quality of life	AQLQ(S)+12; EQ-5D-5L	Immediately following the first administration of study drug through Study Week 48.	No
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on health care resource utilization and productivity loss due to asthma	WPAI+CIQ; Asthma specific resource utilization (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications)	Immediately following the first administration of study drug through Study Week 48	No
Secondary	Assessment of the effect of 2 dosing regimens of benralizumab on overall response to treatment	CGIC and PGIC assessments	Immediately following the first administration of study drug through Study Week 48	No