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This is a Phase 1, randomized, single-blind study in healthy Chinese subjects at single dose administration of benralizumab: Treatment 1, Treatment 2 and Treatment 3. The study design allows an assessment of 3 doses with safety monitoring and PK sampling to evaluate the safety, tolerability and PK profile of benralizumab.
This study will be conducted at 1 study center in Hong Kong. Approximately 36 healthy Chinese male and female subjects, aged 18 to 45 inclusive, will be randomized in a 1:1:1 ratio to receive a single SC administration of benralizumab: Treatment 1, Treatment 2 and Treatment 3 (12 subjects per group). Each subject will participate in only 1 treatment group. Approximately 8-12 evaluable subjects in each group that met specific non-compartmental analysis (NCA) criteria are required to ensure eligible AUC0-∞ calculation. The total length of the study for each subject is up to 117 days (28 days of screening and 85+/- 4 days of further study visits).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Benralizumab - Subcutaneous administration of Dose 1 | Experimental | Benralizumab single dose administration subcutaneously |
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| Benralizumab - Subcutaneous administration of Dose 2 | Experimental | Benralizumab single dose administration subcutaneously |
|
| Benralizumab - Subcutaneous administration of Dose 3 | Experimental | Benralizumab single dose administration subcutaneously |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benralizumab | Biological | Treatment 1: Benralizumab single dose, Treatment 2: Benralizumab single dose and Treatment 3: Benralizumab single dose subcutaneously administration on 36 healthy Chinese male and female subjects in 1:1:1 ratio. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with Adverse events (AEs) and serious adverse events (SAEs) | The number and percentage of subjects with treatment-emergent AE/SAE/AE by severity/drug-related AE/drug-related SAE/death in each dose level group and overall. AE/SAE will be displayed by MedDRA SOC and/or PT. | Day (-1) to Day 85 |
| Safety as determined by abnormality in haematology | Measurement of red blood cell count, white blood cell count, haemoglobin and platelets | Day (-1) to Day 85 |
| Safety as determined by abnormality in clinical chemistry | Measurement of kidney function (e.g.urea ,creatinine, Uric acid), liver function(ALP, ALT, AST, albumin, total bilirubin), lipid profile(total cholesterol, triglycerides), potassium. | Day (-1) to Day 85 |
| Safety as determined by abnormality in urinalysis | Measurement of glucose, ketones, leukocytes, blood and protein | Day (-1) to Day 85 |
| Safety as determined by evaluation of blood pressure in mmHg | Measurement of blood pressure (systolic and diastolic in mmHg) | Day (-1) to Day 85 |
| Safety as determined by evaluation of Pulse rate in beats per minute | Measurement of Pulse rate in beats per minute | Day (-1) to Day 85 |
| Safety as determined by evaluation of body temperature in degree Celsius |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed concentration (Cmax) | To assess the Pharmacokinetic profile of Subcutaneously administration of benralizumab in healthy Chinese subjects. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tsang Tommy Cheung, MBBS | HKU Phase 1 Clinical Trials Centre, 2/F, Block K, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Hong Kong | Hong Kong |
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| ID | Term |
|---|---|
| C571386 | benralizumab |
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36 healthy Chinese male and female subjects randomized in a 1:1:1 ratio to receive a single SC administration of benralizumab, Treatment 1, Treatment 2 and Treatment 3 (12 subjects per group). Each subject will participate in only 1 treatment group.
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Measurement of body temperature in degree Celsius
| Day (-1) to Day 85 |
| Safety as determined by analysis of 12-lead ECG variables: heart rate (beats per minute) | The ECG variables will be summarized by absolute value at each visit by treatment group, together with the corresponding changes from baseline. | Day (-1) to Day 85 |
| Safety as determined by analysis of 12-lead ECG variables: PR, QRS, QT and QTcF (milliseconds) | The ECG variables will be summarized by absolute value at each visit by treatment group, together with the corresponding changes from baseline. | Day (-1) to Day 85 |
| Time to maximum observed concentration (tmax) |
To assess the Pharmacokinetic profile of subcutaneously administration of benralizumab in healthy Chinese subjects. |
| Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85. |
| Area under the concentration-time curve from 0 to the last measurable time point (AUC0-t) | To assess the Pharmacokinetic profile of subcutaneously administration benralizumab in healthy Chinese subjects. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85. |
| Area under the concentration-time curve from 0 to infinity (AUC0-∞) | To assess the Pharmacokinetic profile of subcutaneously administration benralizumab in healthy Chinese subjects. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85. |
| Apparent clearance (CL/F) | To assess the Pharmacokinetic profile of subcutaneously administration benralizumab in healthy Chinese subjects. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85. |
| Apparent volume of distribution at terminal phase (Vz/F) | To assess the Pharmacokinetic profile of subcutaneously administration benralizumab in healthy Chinese subjects. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85. |
| Time for concentration to decrease by 50% (concentration half-life) (t1/2) | To assess the Pharmacokinetic profile of subcutaneously administration benralizumab in healthy Chinese subjects. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 2, Day 4, Day 5, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 and Day 85. |
| Anti-drug antibody (ADA) as determined by evaluation of ADA positive percentage and ADA negative percentage | To assess the immunogenicity of benralizumab. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 29, Day 57 and Day 85. |
| All ADA positive samples will be tested for neutralizing antibodies (nAb). nAb as determined by evaluation of nAb positive percentage | To assess the immunogenicity of benralizumab. | Blood samples will be collected from Day 1 (1 hour prior to administration of IP) and on Day 29, Day 57 and Day 85. |