Pharmacokinetic Study of Benralizumab in Healthy Chinese Subjects

NCT03928262 | Completed Phase 1

• 1 other identifier: D3250C00034
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

Pharmacokinetics; Safety; Tolerability; Benralizumab; Healthy Chinese subjects

Outcome Measures

Primary Outcomes (9)

• 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

  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

Secondary Outcomes (9)

• Maximum observed concentration (Cmax)

  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 to maximum observed concentration (tmax)

  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)

  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-∞)

  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)

  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.

Study Arms (3)

Benralizumab - Subcutaneous administration of Dose 1

EXPERIMENTAL

Benralizumab single dose administration subcutaneously

Biological: Benralizumab

Benralizumab - Subcutaneous administration of Dose 2

EXPERIMENTAL

Benralizumab single dose administration subcutaneously

Biological: Benralizumab

Benralizumab - Subcutaneous administration of Dose 3

EXPERIMENTAL

Benralizumab single dose administration subcutaneously

Biological: Benralizumab

Interventions

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.

Benralizumab - Subcutaneous administration of Dose 1; Benralizumab - Subcutaneous administration of Dose 2; Benralizumab - Subcutaneous administration of Dose 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be willing and able to give written informed consent by signing an IRB/IEC approved Informed Consent Form (ICF) and follow the restrictions and procedures outlined for the study.
• Healthy adult males or females as determined by medical history, physical examination, and laboratory tests. Subjects age between 18 to 45 years old (inclusive) at the time of signing informed consent. Subject is a Han Chinese who were born in China (including Hong Kong) with Han Chinese parents and grandparents who were born in China (including Hong Kong)
• Have a body mass index (BMI) between 19 and 24 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg.
• Medically healthy subjects with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms \[ECGs\], physical examination). Haemoglobin must be greater than the lower limit of normal. A 12-lead ECG with QTc \>340 msec and \<450 msec.
• Women of childbearing potential (WOCBP) must have a negative urine pregnancy test prior to administration of the IP and use an effective form of birth control (confirmed by the Investigator or designee). Highly effective forms of birth control include: true sexual abstinence, a vasectomised sexual partner, Implanon, female sterilization by tubal occlusion, any effective IUD Intrauterine device/IUS Ievonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch ™ or Nuvaring™. WOCBP must agree to use an effective method of birth control, as defined above, from enrolment, throughout the study duration and within 16 weeks (5 half-lives or longer) after the dosing and have negative serum or urine pregnancy test result on Visit 1 and Visit 2.
• Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Male subjects should be willing to use condoms, in association with another method of contraception, from the day of the first dosing until 16 weeks (5 half-lives or longer) after the dosing.

You may not qualify if:

• Any subject with a history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or neurological disorder that is capable of altering the metabolism or elimination of drugs or that constitutes a risk factor when taking the study medication.
• Any subject with a documented history of disorders of the immune system at any time.
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with or has failed to respond to standard of care therapy.
• Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1.
• Any subject with a clinically significant relevant deviation from normal in physical examination, electrocardiography, or clinical laboratory tests, as determined by the Principal Investigator.
• Any clinical significant findings off Chest x-rays or CT image. If a chest X-ray or CT has not been performed within 6 months prior to screening visit, a chest X-ray must be performed before the IP administration.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \> the upper limit of normal (ULN).
• Positive result on screening for serum hepatitis B surface antigen, or hepatitis C antibody. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
• Any subject with any condition resulting in an increased eosinophil count at screening.
• Any condition requiring the regular use of any medication.
• Any subject requiring a prescription medication, other than contraceptives. Subjects taking nonprescription medications must be willing and able to refrain from their use during the inpatient period of the study.
• Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, systemic corticosteroid for condition other than short course for nasal polyps, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained, and during the study period.
• Receipt of any marketed or investigational biologic (monoclonal or polyclonal antibody) within 4 months or 5 half-lives prior to the date informed consent, is obtained, whichever is longer, and during the study period. E.g. Previous receipt of mepolizumab, reslizumab, dupilumab, or benralizumab.
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
• Receipt of live attenuated vaccines 30 days prior to the date of informed consent.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Hong Kong, Hong Kong

Location

MeSH Terms

Interventions

benralizumab

Study Officials

• Tsang Tommy Cheung, MBBS

  HKU Phase 1 Clinical Trials Centre, 2/F, Block K, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: April 26, 2019
• Study Start: April 2, 2019
• Primary Completion: August 12, 2019
• Study Completion: August 12, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)