A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers

A Single-Center, Open-Label, Single Dose Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Healthy Volunteers
• Intervention / Treatment: Drug: Emicizumab

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100083
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Emicizumab	Drug: Emicizumab; Participants will receive a single 1 milligram per kilogram of body weight (mg/kg) subcutaneous dose of emicizumab on Day 1.; Other Names: RO5534262

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Area Under the Plasma Concentration Versus Time Curve (AUC) Between Time Zero Extrapolated to Infinity (AUC0-inf) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC Between Time Zero and the Time of Last Quantifiable Concentration (AUC0-last) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Time to Cmax (Tmax) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Apparent Terminal Half-Life (t1/2) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Apparent Clearance (CL/F) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Apparent Volume of Distribution (Vz/F) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Mean Residence Time (MRT) of Emicizumab	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Number of Participants With Adverse Events by Highest World Health Organization (WHO) Toxicity Grade	The WHO Toxicity Grading Scale was used for assessing adverse event severity. Any adverse event not specifically listed in the WHO Toxicity Grading Scale was assessed according to the following levels of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; and Grade 4 is life-threatening. Investigator text for adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. After informed consent had been obtained but prior to initiation of study drug, only serious adverse events (SAEs) caused by a protocol-mandated intervention were to have been reported. After initiation of study drug, all adverse events, regardless of relationship to study drug, were to have been reported until the participant completed his last study visit. After this period, any SAEs believed to be related to prior study drug treatment were to be reported.	From screening to study completion (20 weeks)
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADA) Against Emicizumab by Timepoint and for the Overall Study	Participants were considered to be 'ADA Negative (Treatment Unaffected)' if baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample. 'Total ADA Positive' is the sum of all participants who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Induced)', those who were ADA negative at baseline and tested positive for ADA following study drug administration; and 'ADA Positive (Treatment Boosted)', those who were pre-dose ADA positive and had post-baseline samples with a titer that was at least 4-fold greater compared to the baseline measurement.	Predose at Baseline (Day 1) and postdose on Days 57 and 113
Number of Participants With Laboratory Test Abnormalities	The number of participants with a laboratory abnormality during treatment (numerator) is reported among the 'number analyzed' in the table below (denominator), which represents the number of participants without that abnormality at baseline (last observation prior to initiation of study drug). Note that samples from all participants were analyzed for each laboratory parameter. Values falling above or below the Roche predefined standard reference range were laboratory abnormalities labelled accordingly as 'high' or 'low'. Not every laboratory abnormality qualified as an adverse event; only if it was accompanied by clinical symptoms, resulted in a change in study treatment or in a medical intervention, or was clinically significant in the investigator's judgment. SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase	Baseline and Days 2, 4, 8, 11, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Albumin Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Bilirubin Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Blood Glucose Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Blood Urea Nitrogen Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: C-Reactive Protein Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Chloride Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Cholesterol Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatine Kinase Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatinine Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Direct Bilirubin Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Gamma Glutamyl Transferase Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Lactate Dehydrogenase Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Potassium Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Total Protein Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGOT/AST Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGPT/ALT Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Sodium Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Triglycerides Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Uric Acid Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Activated Partial Thromboplastin Time	Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 11, 29, 57, and 113
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Fibrinogen Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 11, 29, 57 and 113
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time	Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 11, 29, 57 and 113
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time/International Normalized Ratio (INR)	The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 11, 29, 57 and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils, Absolute Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils, Absolute Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin	Erythrocyte mean corpuscular hemoglobin (MCH) is a measure of the average amount of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Volume	Erythrocyte mean corpuscular volume is a measure of the average volume of a red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin Concentration	Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit (as a Fraction of 1)	Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin Concentration	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes, Absolute Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes, Absolute Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Total Neutrophils, Absolute Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Platelet Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113
Number of Participants by Test Results for Blood in Urine by Timepoint	Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for blood in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 8, 29, 57, 85, and 113
Number of Participants by Test Results for Glucose in Urine by Timepoint	Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for glucose in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 8, 29, 57, 85, and 113
Number of Participants by Test Results for Protein in Urine by Timepoint	Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for protein in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug.	Baseline and Days 2, 8, 29, 57, 85, and 113
Change From Baseline in Vital Signs by Timepoint: Diastolic Blood Pressure	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Change From Baseline in Vital Signs by Timepoint: Pulse Rate	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Change From Baseline in Vital Signs by Timepoint: Respiratory Rate	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Change From Baseline in Vital Signs by Timepoint: Systolic Blood Pressure	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Change From Baseline in Vital Signs by Timepoint: Temperature (Axillary)	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113
Change From Baseline in Electrocardiogram (ECG) Results by Timepoint: Heart Rate	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in ECG Results by Timepoint: PR Duration	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in ECG Results by Timepoint: QRS Duration	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in ECG Results by Timepoint: QT Duration	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in ECG Results by Timepoint: QTcB Duration (Bazett's Correction Formula)	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in ECG Results by Timepoint: QTcF Duration (Fridericia's Correction Formula)	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Change From Baseline in ECG Results by Timepoint: RR Duration	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113
Number of Participants With Concomitant Medications	The original terms recorded by the investigator for concomitant medications were standardized by the sponsor by assigning preferred terms. The duration of treatment with the concomitant medications ranged from 1 day to 5 days. Except for 1 participant who was treated during the in-clinic period (Days -1 to 4), all other concomitant medications were recorded during the ambulatory period (Days 6 to 113).	From screening to study completion (20 weeks)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2018
• Primary Completion (Actual): September 18, 2018
• Study Completion (Actual): September 18, 2018

Study Registration Dates

• First Submitted: December 13, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 3, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: YP39308

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No