A Phase 2a Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Adults With Asthma

MedImmune

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Other: Placebo; Biological: Benralizumab 100 mg; Biological: Benralizumab 200 mg; Biological: Benralizumab 25 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00783289

MI-CP197

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety and tolerability of escalating multiple subcutaneous (SC) doses of MEDI-563 in adult subjects with asthma.

Full description

This is a Phase 2a, randomized, double-blind, placebo-controlled, dose-escalation, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of multiple subcutaneous doses (25, 100, or 200 milligram [mg]) of benralizumab (MEDI-563) in adult subjects with asthma.

Enrollment: 35 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female subjects
• Age 18 through 80 years at screening
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Previously documented diagnosis of asthma of more than or equal to (>=) 1 year duration, based on episodic symptoms of airflow obstruction; post-bronchodilator reversibility of airflow obstruction >=12 percent (%) (at screening or documented within 1 year prior to randomization); or proof of a positive response to a methacholine challenge (documented within 1 year prior to randomization) as represented by a provoking concentration of methacholine to cause a 20% fall in forced expiratory volume in 1 second (FEV1); (PC20) less than (<) 8 milligram per milliliter (mg/mL)
• Weight of >=45 kilogram (kg) but less than or equal to (<=) 135 kg (>=100 pounds [lb] but <=300 lb)
• Able to produce spirometry readings that meet American Thoracic Society (ATS)/European Respiratory Society (ERS) standards
• Screening pre-bronchodilator FEV1 >=60%
• Women of childbearing potential, unless surgically sterile (including tubal ligation) and/or at least 2 years post-menopausal, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, abstinence, use of a condom with spermicide by the sexual partner, or sterile sexual partner) for 14 days prior to the first dose of the investigational product on Study Day 0, and must agree to continue using such precautions through Study Day 161. Cessation of birth control after this point should be discussed with a responsible physician
• Men, unless surgically sterile, must likewise use 2 effective methods of birth control (for example, condom with spermicide) and must agree to continue using such contraceptive precautions through End of Study/Study Day 161
• Ability to complete the study period, including follow-up period until Study Day 161 as required by protocol

Exclusion criteria

• Previously received benralizumab (MEDI-563)
• History of allergy or reaction to any component of the investigational product formulation
• History of allergy or reaction to any other marketed or experimental monoclonal antibody therapies, intravenous gammaglobulin (IVIG), or blood products
• Receipt of any investigational drug therapy within 30 days prior to randomization into the study or any biologic(s) within 5 half-lives of the agent prior to randomization into the study
• Treatment with an oral or systemic burst of corticosteroids within 4 weeks prior to randomization into the study
• Use of any chronic systemic immunosuppressive drugs, including oral corticosteroids within 4 weeks prior to randomization into the study
• Current use of any oral or ophthalmic beta-adrenergic antagonist (for example, propranolol), must have been stopped 2 weeks prior to randomization into the study
• Current allergy vaccination (immunotherapy)
• History of anaphylaxis
• Lung disease other than persistent asthma (for example, chronic bronchitis, cystic fibrosis, chronic obstructive pulmonary disease [COPD], tuberculosis [TB])
• Acute illnesses or evidence of significant active infection, such as fever >=38.0 degrees Celsius [C] (>=100.5 degrees Fahrenheit [F]) at screening and up through time of the first dose of the investigational product
• History of ingestion of untreated water in a location known to be infected with parasites, resulting in acute or chronic diarrhea; or an untreated parasitic infection within 1 month of randomization
• Pregnancy (women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to administration of the investigational product)
• Lactating woman
• Infection with human immunodeficiency virus (HIV)-1, HIV-2, or hepatitis A, B, or C virus
• History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy >= 1 year prior to randomization into the study
• History of cigarette smoking >=10 pack years
• History of alcohol abuse or drug abuse that required treatment <1 year prior to randomization into the study
• Elective surgery planned during the study period
• Evidence of any systemic disease or any finding upon physical examination, laboratory abnormality, chest x-ray (CXR), or electrocardiogram (ECG) that, in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or confound the analysis of the study results
• Employees of the clinical study site or any other individuals involved with the conduct of the study, or first degree family members of such individuals (that is, parents, siblings, or children)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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35 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.

Treatment:

Other: Placebo

Benralizumab 25 mg

Experimental group

Description:

Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.

Treatment:

Biological: Benralizumab 25 mg

Benralizumab 100 mg

Experimental group

Description:

Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.

Treatment:

Biological: Benralizumab 100 mg

Benralizumab 200 mg

Experimental group

Description:

Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.

Treatment:

Biological: Benralizumab 200 mg