Phase 1
N=16
A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers
Healthy Volunteers · Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT03380780 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Sep 2019
Primary outcome: Primary: Maximum Observed Plasma Concentration (Cmax) of Emicizumab — 7.11 microgram per milliliter (μg/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Emicizumab (Drug)
- Age
- Adult · 20+ yrs
- Sex
- Male
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Emicizumab |
7.11 | — |
| PRIMARY Area Under the Plasma Concentration Versus Time Curve (AUC) Between Time Zero Extrapolated to Infinity (AUC0-inf) of Emicizumab |
287 | — |
| SECONDARY AUC Between Time Zero and the Time of Last Quantifiable Concentration (AUC0-last) of Emicizumab |
268 | — |
| SECONDARY Time to Cmax (Tmax) of Emicizumab |
7.0 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Emicizumab |
26.7 | — |
| SECONDARY Apparent Clearance (CL/F) of Emicizumab |
235 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of Emicizumab |
8870 | — |
| SECONDARY Mean Residence Time (MRT) of Emicizumab |
40.26 | — |
| SECONDARY Number of Participants With Adverse Events by Highest World Health Organization (WHO) Toxicity Grade |
14; 7; 7; 0; 0; 1 | — |
| SECONDARY Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADA) Against Emicizumab by Timepoint and for the Overall Study |
0; 16; 0; 16; 1; 15 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities |
1; 2; 2; 5; 1; 1 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Albumin Concentration |
45.43; -0.43; 1.03; 0.29; 0.08; -0.18 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase Concentration |
85.38; 0.50; 2.50; 1.06; 2.38; 1.44 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Bilirubin Concentration |
13.83; 0.82; -0.42; -1.10; -0.61; -0.56 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Blood Glucose Concentration |
5.03; -0.33; -0.22; -0.16; -0.27; -0.08 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Blood Urea Nitrogen Concentration |
4.46; -0.58; -0.73; 0.26; 0.43; 0.43 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: C-Reactive Protein Concentration |
0.50; 0.23; 0.11; 0.54; 0.75; 1.01 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Chloride Concentration |
104.69; -0.69; -0.63; 0.13; 0.06; -1.56 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Cholesterol Concentration |
3.88; 0.02; 0.07; -0.03; -0.04; 0.03 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatine Kinase Concentration |
121.63; -41.13; -25.81; -22.19; -0.94; 8.50 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatinine Concentration |
83.19; -0.56; -0.31; -1.25; -2.00; -3.69 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Direct Bilirubin Concentration |
1.63; 0.56; 0.29; 0.00; -0.07; 0.12 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Gamma Glutamyl Transferase Concentration |
19.94; -0.50; 0.13; 0.19; -0.13; -0.13 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Lactate Dehydrogenase Concentration |
153.75; -10.13; -0.19; 3.19; 3.19; 6.56 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Potassium Concentration |
4.27; 0.11; -0.03; 0.12; -0.02; -0.05 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Total Protein Concentration |
70.55; -0.18; 2.69; 1.36; 0.81; 1.03 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGOT/AST Concentration |
16.63; -0.81; 1.13; 0.69; 0.19; 1.13 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGPT/ALT Concentration |
15.63; -0.31; 2.19; 2.19; -0.13; 0.25 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Sodium Concentration |
140.56; -0.44; -0.44; -0.06; 0.25; -1.75 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Triglycerides Concentration |
0.98; 0.37; 0.57; 0.03; 0.22; 0.15 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Uric Acid Concentration |
323.44; 21.38; -15.06; -2.88; 2.44; 2.31 | — |
| SECONDARY Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Activated Partial Thromboplastin Time |
31.63; -2.79; -4.82; -3.63; -2.14; -0.70 | — |
| SECONDARY Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Fibrinogen Concentration |
2.43; 0.18; 0.28; 0.11; 0.05; 0.07 | — |
| SECONDARY Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time |
11.33; 0.00; -0.09; -0.18; -0.18; -0.17 | — |
| SECONDARY Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time/International Normalized Ratio (INR) |
1.06; 0.00; -0.01; -0.02; -0.02; -0.02 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils, Absolute Count |
0.02; 0.00; 0.01; 0.01; 0.01; 0.01 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils, Absolute Count |
0.14; 0.02; 0.01; 0.00; -0.01; -0.01 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin |
30.84; 0.23; 0.09; 0.26; -0.12; 0.04 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Volume |
89.79; -0.14; 0.01; 0.21; 0.88; -0.08 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin Concentration |
343.25; 3.13; 1.00; 2.31; -4.56; 0.69 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit (as a Fraction of 1) |
0.44; 0.01; 0.01; 0.00; 0.00; -0.01 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin Concentration |
149.38; 3.94; 5.38; 0.88; -2.50; -2.50 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes, Absolute Count |
1.65; 0.10; 0.37; 0.04; -0.09; -0.01 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes, Absolute Count |
0.35; -0.04; -0.03; -0.04; -0.01; -0.01 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Total Neutrophils, Absolute Count |
3.57; -0.24; 0.12; -0.19; 0.19; 0.23 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Platelet Count |
231.50; -2.13; -3.69; 0.06; 7.25; 12.50 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count |
4.86; 0.09; 0.16; -0.02; -0.07; -0.09 | — |
| SECONDARY Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count |
5.74; -0.17; 0.33; -0.20; 0.09; 0.21 | — |
| SECONDARY Number of Participants by Test Results for Blood in Urine by Timepoint |
15; 1; 0; 0; 16; 0 | — |
| SECONDARY Number of Participants by Test Results for Glucose in Urine by Timepoint |
16; 0; 0; 0; 16; 0 | — |
| SECONDARY Number of Participants by Test Results for Protein in Urine by Timepoint |
16; 0; 0; 0; 16; 0 | — |
| SECONDARY Change From Baseline in Vital Signs by Timepoint: Diastolic Blood Pressure |
66.1; -0.8; 2.4; 3.2; 2.7; 1.4 | — |
| SECONDARY Change From Baseline in Vital Signs by Timepoint: Pulse Rate |
61.3; -0.6; 1.3; 5.8; 7.7; 9.9 | — |
| SECONDARY Change From Baseline in Vital Signs by Timepoint: Respiratory Rate |
15.5; 0.6; 0.3; -0.5; 0.8; 0.1 | — |
| SECONDARY Change From Baseline in Vital Signs by Timepoint: Systolic Blood Pressure |
106.8; -1.6; 2.4; 3.6; 3.5; 5.1 | — |
| SECONDARY Change From Baseline in Vital Signs by Timepoint: Temperature (Axillary) |
36.20; -0.12; 0.01; -0.09; -0.08; -0.18 | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Results by Timepoint: Heart Rate |
59.90; -0.67; 2.50; 6.52; 8.63; 6.58 | — |
| SECONDARY Change From Baseline in ECG Results by Timepoint: PR Duration |
160.21; 0.81; -0.10; -1.90; -4.13; -1.73 | — |
| SECONDARY Change From Baseline in ECG Results by Timepoint: QRS Duration |
98.15; 0.75; 1.40; -0.71; -0.48; -0.40 | — |
| SECONDARY Change From Baseline in ECG Results by Timepoint: QT Duration |
398.31; -1.35; -10.00; -12.31; -15.69; -9.90 | — |
| SECONDARY Change From Baseline in ECG Results by Timepoint: QTcB Duration (Bazett's Correction Formula) |
398.04; -3.81; -2.29; 7.33; 10.08; 10.50 | — |
| SECONDARY Change From Baseline in ECG Results by Timepoint: QTcF Duration (Fridericia's Correction Formula) |
397.90; -2.98; -4.94; 1.21; 1.31; 3.56 | — |
| SECONDARY Change From Baseline in ECG Results by Timepoint: RR Duration |
1001.06; 12.73; -36.04; -94.79; -119.67; -96.56 | — |
| SECONDARY Number of Participants With Concomitant Medications |
6; 1; 1; 1; 1; 1 | — |
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
Data sourced from ClinicalTrials.gov (NCT03380780). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.