Clinical trial NCT03380780: A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers
Official title: A Single-Center, Open-Label, Single Dose Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Hemophilia A
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-12-21
Enrollment: 16
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single-center, open-label study will evaluate the pharmacokinetics, safety, and tolerability of emicizumab following a single subcutaneous (SC) administration to healthy Chinese subjects.


Eligibility criteria: Inclusion Criteria:

* Healthy Chinese male subjects, aged 20-45 years inclusive at the time of screening
* Chinese subjects must have Chinese parents and grandparents, all of whom were born in China
* A body mass index (BMI) between 19 and 24 kilograms per height in meters squared (kg/m\^2), inclusive
* Able to participate and willing to give written informed consent and to comply with the study requirements

Exclusion Criteria:

* Any history or presence of a clinically significant disorder, or any other condition or disease which in the judgement of the investigator would place the subject at undue risk; interfere with absorption, distribution, metabolism, and excretion of emicizumab; or interfere with the ability of the subject to complete the study
* Major illness within 1 month prior to dosing, and/or any condition which could relapse during or immediately after the study
* Use of any prescribed or over-the-counter (OTC) medication or herbal medicine taken within 14 days prior to dosing or within 5 times the elimination half-life of the medication prior to dosing (whichever is longer), with some exceptions
* Any significant donation/loss of blood or plasma (greater than 450 milliliters) within the 3 months prior to dosing
* Regular smoker with consumption of more than 10 cigarettes per day or the equivalent amount of tobacco
* Participation within a clinical study with an investigational drug or device within the last 3 months prior to dosing
* Any clinically relevant history of hypersensitivity or allergic reactions, either spontaneous or following drug administration or exposure to foods or environmental agents
* Previous or concomitant thromboembolic disease such as deep vein thrombosis (DVT) or signs of thromboembolic disease, or family history of thromboembolic disorder such as serious DVT
* At high risk for thrombotic microangiopathy (e.g., have a previous medical or family history of thrombotic microangiopathy), in the investigator's judgment
* Previous or concomitant autoimmune or connective tissue disease
* History of tuberculosis or active tuberculosis with positive test result at screening
* Any other reason that, in the judgment of the investigator, would render the subject unsuitable for study participation

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) Between Time Zero Extrapolated to Infinity (AUC0-inf) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Secondary outcomes:
measure: AUC Between Time Zero and the Time of Last Quantifiable Concentration (AUC0-last) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Time to Cmax (Tmax) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Apparent Terminal Half-Life (t1/2) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Apparent Clearance (CL/F) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Apparent Volume of Distribution (Vz/F) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Mean Residence Time (MRT) of Emicizumab
timeFrame: Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Number of Participants With Adverse Events by Highest World Health Organization (WHO) Toxicity Grade
timeFrame: From screening to study completion (20 weeks)
measure: Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADA) Against Emicizumab by Timepoint and for the Overall Study
timeFrame: Predose at Baseline (Day 1) and postdose on Days 57 and 113
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline and Days 2, 4, 8, 11, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Albumin Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Bilirubin Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Blood Glucose Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Blood Urea Nitrogen Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: C-Reactive Protein Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Chloride Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Cholesterol Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatine Kinase Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatinine Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Direct Bilirubin Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Gamma Glutamyl Transferase Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Lactate Dehydrogenase Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Potassium Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Total Protein Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGOT/AST Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGPT/ALT Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Sodium Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Triglycerides Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Uric Acid Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Activated Partial Thromboplastin Time
timeFrame: Baseline and Days 2, 11, 29, 57, and 113
measure: Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Fibrinogen Concentration
timeFrame: Baseline and Days 2, 11, 29, 57 and 113
measure: Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time
timeFrame: Baseline and Days 2, 11, 29, 57 and 113
measure: Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time/International Normalized Ratio (INR)
timeFrame: Baseline and Days 2, 11, 29, 57 and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils, Absolute Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils, Absolute Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Volume
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit (as a Fraction of 1)
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin Concentration
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes, Absolute Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes, Absolute Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Total Neutrophils, Absolute Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Platelet Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count
timeFrame: Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Number of Participants by Test Results for Blood in Urine by Timepoint
timeFrame: Baseline and Days 2, 8, 29, 57, 85, and 113
measure: Number of Participants by Test Results for Glucose in Urine by Timepoint
timeFrame: Baseline and Days 2, 8, 29, 57, 85, and 113
measure: Number of Participants by Test Results for Protein in Urine by Timepoint
timeFrame: Baseline and Days 2, 8, 29, 57, 85, and 113
measure: Change From Baseline in Vital Signs by Timepoint: Diastolic Blood Pressure
timeFrame: Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Change From Baseline in Vital Signs by Timepoint: Pulse Rate
timeFrame: Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Change From Baseline in Vital Signs by Timepoint: Respiratory Rate
timeFrame: Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Change From Baseline in Vital Signs by Timepoint: Systolic Blood Pressure
timeFrame: Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Change From Baseline in Vital Signs by Timepoint: Temperature (Axillary)
timeFrame: Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
measure: Change From Baseline in Electrocardiogram (ECG) Results by Timepoint: Heart Rate
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in ECG Results by Timepoint: PR Duration
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in ECG Results by Timepoint: QRS Duration
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in ECG Results by Timepoint: QT Duration
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in ECG Results by Timepoint: QTcB Duration (Bazett's Correction Formula)
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in ECG Results by Timepoint: QTcF Duration (Fridericia's Correction Formula)
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Change From Baseline in ECG Results by Timepoint: RR Duration
timeFrame: Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
measure: Number of Participants With Concomitant Medications
timeFrame: From screening to study completion (20 weeks)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: