Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma

MedImmune

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Other: Placebo; Biological: Benralizumab 100 mg; Biological: Benralizumab 2 mg; Biological: Benralizumab 20 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01238861

2010-020126-17 (EudraCT Number)

MI-CP220

Details and patient eligibility

About

The primary objective of the study is to evaluate the effect of multiple-dose subcutaneous administrations of MEDI-563 on adults with uncontrolled asthma.

Full description

This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of multiple-dose (7 doses) subcutaneous administration of benralizumab (MEDI-563) in adult subjects with uncontrolled asthma.

Enrollment: 964 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 through 75 years at the time of screening
• Adequate contraception from screening through end of trial
• Weight of more than (>) 45 kilogram (kg) but less than or equal to (<=) 150 kg (>100 pound [lb] but <=330 lb)
• History of physician-diagnosed asthma for at least 12 months prior to screening
• Physician prescribed daily use of medium-dose or high-dose inhaled corticosteroid(s) (ICS) plus long-acting beta 2 agonist (LABA) for at least 12 months prior to screening
• Willingness to switch to an ICS/LABA combination product
• Dose of other asthma controller medications must be stable for at least 30 days prior to screening
• At least 2 documented asthma exacerbations in the 12 months prior to screening that required use of a systemic corticosteroid burst
• For subjects 65 years of age or older, a chest x-ray (CXR) or chest computed tomography (CT) that is normal for an asthmatic population
• Ability and willingness to complete the study to Week 66, and if needed to Week 92.

Exclusion criteria

• Known history of allergy or reaction to any component of the investigational product formulation
• History of anaphylaxis to any biologic therapy
• Unexplained diarrhea within 30 days prior to screening or diagnosis of helminth parasitic infestation within 6 months prior to screening
• Use of immunosuppressive medication within 3 months prior to screening. Chronic oral prednisone or equivalent up to 10 milligram (mg) daily or 20 mg every other day for asthma is allowed
• Oral corticosteroid burst or short-acting systemic corticosteroid within 30 days prior to screening or during the screening/run-in period
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to the screening or during the screening/run-in period
• Receipt of immunoglobulin or blood products within 30 days prior to screening
• Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to screening, whichever is longer
• Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to screening, whichever is longer
• Previously received MEDI-563
• Any clinically relevant abnormal findings in physical examination
• Past history of clinically significant cardiac disease or any electrocardiogram (ECG) abnormality
• Breastfeeding or lactating women
• History of alcohol or drug abuse within 12 months prior to screening
• History of any known primary immunodeficiency disorder
• Positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol
• A positive human immunodeficiency virus (HIV) test or subject taking antiretroviral medications
• History of cigarette smoking more than or equal to (>=) 10 pack-years or smoking within 12 months prior to screening.
• Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma
• History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy >=12 months prior to screening or other malignancies treated with apparent success with curative therapy >=5 years prior to screening
• Stable dose of allergy vaccination regimen for less than 30 days prior to screening
• Subjects unable to demonstrate acceptable inhaler and peak flow meter techniques.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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964 participants in 6 patient groups, including a placebo group

Eosinophilic phenotype (EOS+) Placebo

Placebo Comparator group

Description:

EOS+ (defined as ELEN Index \[proprietary mathematical algorithm to predict sputum eosinophil's greater than or equal to 2 percent\] positive and/or FeNO \[fraction of exhaled nitric oxide\] greater than or equal to \[\>=\] 50 parts per billion \[ppb\]) participants received matching placebo injections subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Treatment:

Other: Placebo

EOS+ Benralizumab (2 mg)

Experimental group

Description:

EOS+ participants received single benralizumab 2 milligram (mg) injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Treatment:

Biological: Benralizumab 2 mg

EOS+ Benralizumab (20 mg)

Experimental group

Description:

EOS+ participants received single benralizumab 20 mg injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Treatment:

Biological: Benralizumab 20 mg

EOS+ Benralizumab (100 mg)

Experimental group

Description:

EOS+ participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Treatment:

Biological: Benralizumab 100 mg

Non-eosinophil phenotype (EOS-) Placebo

Placebo Comparator group

Description:

EOS- (defined as ELEN Index negative and FeNO \<50 ppb) participants received matching placebo subcutaneous every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Treatment:

Other: Placebo

EOS- Benralizumab (100 mg)

Experimental group

Description:

EOS- participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.

Treatment:

Biological: Benralizumab 100 mg