Asthma
Conditions
Keywords
Asthma, Benralizumab, MEDI-563
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.
Interventions
OTHERPlacebo
Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.
BIOLOGICALBenralizumab 25 mg
Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.
BIOLOGICALBenralizumab 100 mg
Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.
BIOLOGICALBenralizumab 200 mg
Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 0 to Day 161 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Day 161 that were absent before treatment or that worsened relative to pre-treatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) for Benralizumab | Day 0, 1, 7, 28, 35, 56, 84, 112, and 161 | — |
| Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab | Day 0, 1, 7, 28, 35, 56, 84, 112, and 161 | Area under the serum concentration-time curve from time-zero extrapolated to infinity postdose. |
| Terminal Phase Elimination Half-Life (t1/2) for Benralizumab | Day 0, 1, 7, 28, 35, 56, 84, 112, and 161 | Terminal phase elimination half-life (t1/2) is the time measured for the serum concentration to decrease by one half. |
| Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit | Day 0, 28, 56, 84, 112, and 161 | — |
| Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab | Day 0, 1, 7, 28, 35, 56, 84, 112, and 161 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56. | 6 |
| Benralizumab 25 mg Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56. | 7 |
| Benralizumab 100 mg Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56. | 6 |
| Benralizumab 200 mg Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56. | 6 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Benralizumab 25 mg | Benralizumab 100 mg | Benralizumab 200 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 11.2 | 50.4 years STANDARD_DEVIATION 12.3 | 45.5 years STANDARD_DEVIATION 13.4 | 40.2 years STANDARD_DEVIATION 12.5 | 45.6 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 4 / 7 | 4 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Day 161 that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: Day 0 to Day 161
Population: Safety population included all participants who received at least 1 dose of the investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 participants |
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| Benralizumab 25 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| Benralizumab 25 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 participants |
| Benralizumab 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 participants |
| Benralizumab 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| Benralizumab 200 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 participants |
| Benralizumab 200 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
Secondary
Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab
Area under the serum concentration-time curve from time-zero extrapolated to infinity postdose.
Time frame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
Population: Safety population included all participants who received at least 1 dose of the investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab | 118.335 microgram*day per milliliter | Standard Deviation 69.64 |
| Benralizumab 25 mg | Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab | 405.868 microgram*day per milliliter | Standard Deviation 205.856 |
| Benralizumab 100 mg | Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab | 1157.013 microgram*day per milliliter | Standard Deviation 86.444 |
Secondary
Maximum Observed Serum Concentration (Cmax) for Benralizumab
Time frame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
Population: Safety population included all participants who received at least 1 dose of the investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) for Benralizumab | 1.152 microgram per milliliter (mcg/mL) | Standard Deviation 0.615 |
| Benralizumab 25 mg | Maximum Observed Serum Concentration (Cmax) for Benralizumab | 4.127 microgram per milliliter (mcg/mL) | Standard Deviation 1.775 |
| Benralizumab 100 mg | Maximum Observed Serum Concentration (Cmax) for Benralizumab | 15.637 microgram per milliliter (mcg/mL) | Standard Deviation 8.062 |
Secondary
Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit
Time frame: Day 0, 28, 56, 84, 112, and 161
Population: Safety population included all participants who received at least 1 dose of the investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit | 0 participants |
| Benralizumab 25 mg | Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit | 1 participants |
| Benralizumab 100 mg | Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit | 1 participants |
| Benralizumab 200 mg | Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit | 2 participants |
Secondary
Terminal Phase Elimination Half-Life (t1/2) for Benralizumab
Terminal phase elimination half-life (t1/2) is the time measured for the serum concentration to decrease by one half.
Time frame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
Population: Safety population included all participants who received at least 1 dose of the investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Phase Elimination Half-Life (t1/2) for Benralizumab | 17.163 days | Standard Deviation 2.368 |
| Benralizumab 25 mg | Terminal Phase Elimination Half-Life (t1/2) for Benralizumab | 18.610 days | Standard Deviation 3.905 |
| Benralizumab 100 mg | Terminal Phase Elimination Half-Life (t1/2) for Benralizumab | 18.315 days | Standard Deviation 3.484 |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab
Time frame: Day 0, 1, 7, 28, 35, 56, 84, 112, and 161
Population: Safety population included all participants who received at least 1 dose of the investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab | 7.00 days |
| Benralizumab 25 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab | 7.00 days |
| Benralizumab 100 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab | 7.00 days |