Clinical trial NCT00783289: A Phase 2a Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Adults With Asthma
Official title: A Phase 2a, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety and Tolerability of Multiple-dose Subcutaneous Administration of MEDI-563, a Humanized Anti-interleukin-5 Receptor Alpha Monoclonal Antibody, in Adults With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Benralizumab
MEDI-563
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2008-10-31
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 0 to Day 161
Secondary outcomes:
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab
timeFrame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
measure: Maximum Observed Serum Concentration (Cmax) for Benralizumab
timeFrame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
measure: Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab
timeFrame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
measure: Terminal Phase Elimination Half-Life (t1/2) for Benralizumab
timeFrame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
measure: Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit
timeFrame: Day 0, 28, 56, 84, 112, and 161
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Wheaton
country: United States
facility: Research Site
state: Maryland
city: Portland
country: United States
facility: Allergy Associates Research Center
state: Oregon
city: Upland
country: United States
facility: Research Site
state: Pennsylvania
Study officials:
affiliation: MedImmune LLC
name: David Gossage, M.D.
role: STUDY_DIRECTOR
References: