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

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00783289
• Collaborator: (none)
• Enrollment: 35
• Locations: 6
• Arms: 4
• Actual Duration (Months): 12.1
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Other: Placebo; Biological: Benralizumab 25 mg; Biological: Benralizumab 100 mg; Biological: Benralizumab 200 mg	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 14, 2008
• Actual Primary Completion Date: Nov 17, 2009
• Actual Study Completion Date: Nov 17, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.	Other: Placebo; Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.
Experimental: Benralizumab 25 mg Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Biological: Benralizumab 25 mg; Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.; Other Names: MEDI-563
Experimental: Benralizumab 100 mg Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Biological: Benralizumab 100 mg; Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.; Other Names: MEDI-563
Experimental: Benralizumab 200 mg Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.	Biological: Benralizumab 200 mg; Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.; Other Names: MEDI-563

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab [Day 0, 1, 7, 28, 35, 56, 84, 112, and 161]

2. Maximum Observed Serum Concentration (Cmax) for Benralizumab [Day 0, 1, 7, 28, 35, 56, 84, 112, and 161]

3. 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.

4. 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.

5. Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit [Day 0, 28, 56, 84, 112, and 161]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Encinitas	California	United States
2	Research Site	Los Angeles	California	United States
3	Research Site	Colorado Springs	Colorado	United States
4	Research Site	Wheaton	Maryland	United States
5	Allergy Associates Research Center	Portland	Oregon	United States	97213
6	Research Site	Upland	Pennsylvania	United States

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: David Gossage, M.D., MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Attachments tab: MI-CP197 Redacted Protocol_22_Jul_2015

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT00783289
• Other Study ID Numbers: MI-CP197
• First Posted: Oct 31, 2008
• Last Update Posted: Dec 27, 2019
• Last Verified: Dec 1, 2019

• Keywords provided by MedImmune LLC: Asthma; Benralizumab; MEDI-563
• Additional relevant MeSH terms: Asthma; Benralizumab

Study Results

Participant Flow

Arm/Group Title	Placebo	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Period Title: Overall Study
STARTED	6	7	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	1	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg	Total
Arm/Group Description	Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.	Total of all reporting groups
Overall Participants	6	7	6	6	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (11.2)	50.4 (12.3)	45.5 (13.4)	40.2 (12.5)	45.6 (12.2)
Sex: Female, Male (Count of Participants)
Female	3 50%	4 57.1%	4 66.7%	3 50%	14 56%
Male	3 50%	3 42.9%	2 33.3%	3 50%	11 44%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of the investigational product.

Arm/Group Title	Placebo	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Measure Participants	6	7	6	6
TEAEs	3 50%	4 57.1%	4 66.7%	4 66.7%
TESAEs	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Time to Reach Maximum Observed Serum Concentration (Tmax) for Benralizumab
Time Frame	Day 0, 1, 7, 28, 35, 56, 84, 112, and 161

Outcome Measure Data

Analysis Population Description

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/Group Title	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Measure Participants	6	6	6
Median (Full Range) [days]	7.00	7.00	7.00

3. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) for Benralizumab
Time Frame	Day 0, 1, 7, 28, 35, 56, 84, 112, and 161

Outcome Measure Data

Analysis Population Description

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/Group Title	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Measure Participants	6	6	6
Mean (Standard Deviation) [microgram per milliliter (mcg/mL)]	1.152 (0.615)	4.127 (1.775)	15.637 (8.062)

4. Secondary Outcome

Title	Area Under the Curve From Time 0 to Infinity (AUC [0-infinity]) for Benralizumab
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Measure Participants	4	4	4
Mean (Standard Deviation) [microgram*day per milliliter]	118.335 (69.640)	405.868 (205.856)	1157.013 (86.444)

5. Secondary Outcome

Title	Terminal Phase Elimination Half-Life (t1/2) for Benralizumab
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Measure Participants	4	4	4
Mean (Standard Deviation) [days]	17.163 (2.368)	18.610 (3.905)	18.315 (3.484)

6. Secondary Outcome

Title	Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Benralizumab at Any Visit
Time Frame	Day 0, 28, 56, 84, 112, and 161

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of the investigational product.

Arm/Group Title	Placebo	Benralizumab 25 mg	Benralizumab 100 mg	Benralizumab 200 mg
Arm/Group Description	Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.	Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
Measure Participants	6	7	6	6
Number [participants]	0 0%	1 14.3%	1 16.7%	2 33.3%

Adverse Events

Time Frame	Day 0 to Day 161
Arm/Group Title	Placebo		Benralizumab 25 mg		Benralizumab 100 mg		Benralizumab 200 mg
Arm/Group Description	Placebo matched to benralizumab (MEDI-563) injection subcutaneously on Day 0, 28, and 56.		Benralizumab (MEDI-563) injection 25 milligram (mg) subcutaneously on Day 0, 28, and 56.		Benralizumab (MEDI-563) injection 100 mg subcutaneously on Day 0, 28, and 56.		Benralizumab (MEDI-563) injection 200 mg subcutaneously on Day 0, 28, and 56.
All Cause Mortality
	Placebo		Benralizumab 25 mg		Benralizumab 100 mg		Benralizumab 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Benralizumab 25 mg		Benralizumab 100 mg		Benralizumab 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Benralizumab 25 mg		Benralizumab 100 mg		Benralizumab 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		4/7 (57.1%)		4/6 (66.7%)		4/6 (66.7%)
General disorders
Pyrexia	0/6 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Infections and infestations
Bronchitis bacterial	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Gastrointestinal viral infection	0/6 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Oral candidiasis	2/6 (33.3%)	2	0/7 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Oral herpes	0/6 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Postoperative wound infection	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Respiratory tract infection viral	0/6 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Sinobronchitis	0/6 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Upper respiratory tract infection	1/6 (16.7%)	1	0/7 (0%)	0	1/6 (16.7%)	1	2/6 (33.3%)	2
Viral infection	1/6 (16.7%)	1	0/7 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Contusion	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Muscle strain	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Post-traumatic pain	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Procedural pain	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Investigations
Blood creatine phosphokinase increased	1/6 (16.7%)	1	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Blood urea increased	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Troponin i increased	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
White blood cell count decreased	0/6 (0%)	0	1/7 (14.3%)	2	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/6 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	0/6 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Nervous system disorders
Headache	0/6 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/6 (0%)	0	2/7 (28.6%)	3	0/6 (0%)	0	1/6 (16.7%)	2
Nasal congestion	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Sinus congestion	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash papular	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Urticaria	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.