The purpose of this study is to assess the safety and tolerability of MG1113 in the single ascending dose study (IV injection or SC injection) in healthy subjects and hemophiia patients.
This is a single-dose study that explore the safety, tolerability, PK, and PD of the study drug by sequentially increasing the study drug in 4 dose levels. The route of administration is either subcutaneous (SC) injection or intravenous (IV) injection. For healthy subjects, 6 subjects will be assigned to the study group and 2 subjects will be assigned to the placebo group to explore the safety and tolerability, and PK/PD of the study drug in comparison with placebo. Hemophilia patients will be assigned only to the study group with 3 and 6 subjects in each cohort, respectively. The investigator and subjects will know which cohort the healthy subjects have been assigned to, but they will be double-blinded as to whether the subjects are assigned to the study group (study drug) or the placebo group (placebo) within each cohort. The doses planned in healthy subjects are 0.5 mg/kg, 1.7 mg/kg, and 3.3 mg/kg by SC injection; 3.3 mg/kg by IV injection. In hemophilia patients, 1.7 mg/kg and 3.3 mg/kg will be administered by SC injection. The planned dose will be administered after checking the safety and tolerability at the previous dose to the extent not exceeding the criteria for discontinuation of dose escalation. The dose escalation will be decided by the Data Monitoring Committee(DMC) and Data and Safety Monitoring Boards (DSMB) in the blinded evaluation of the safety and tolerability data obtained from each previous cohort for 7 days after administration. Before deciding dose escalation and proceeding to the next step, the safety, tolerability, PK, and PD data obtained from all healty subjects and hemophilia patients up to cohort 6 will be evaluated by the Data and Safety Monitoring Boards (DSMB) in an unblinded manner. In addition, if necessary, the analysis result of cohort that has completed all the scheduled visits can be reviewed in an unblinded manner.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
41
MG1113
Placebo of MG1113
Yonsei Cancer Center, Yonsei University Severance Hospital
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Adverse events
Adverse events such as subjective and objective symptoms
Time frame: Through study completion (~50 day)
Immunogenicity assay
ADA \[Anti-Drug Ab\]
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - Cmax
Cmax
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - Tmax
Tmax
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - AUClast
AUClast
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - AUCinf
AUCinf
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - half-life
half-life
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - CL/F (for SC)
CL/F (for SC)
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - CL (for IV)
CL (for IV)
Time frame: Through study completion (~50 day)
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Pharmacokinetic assessment - Vd/F (for SC)
Vd/F (for SC)
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - Vd (for IV)
Vd (for IV)
Time frame: Through study completion (~50 day)
Pharmacokinetic assessment - Bioavailability (F)
Bioavailability (F) Bioavailability (F) = AUCinf (at SC dosing \[3.3 mg/kg\])/AUCinf (at IV dosing \[3.3 mg/kg\])
Time frame: Through study completion (~50 day)
Pharmacodynamic assessment - Free TFPI in plasma
Free TFPI in plasma (ng/mL)
Time frame: Through study completion (~50 day)
Pharmacodynamic assessment - Diluted PT
Diluted PT (sec)
Time frame: Through study completion (~50 day)
Pharmacodynamic assessment - residual TFPI activity
residual TFPI activity
Time frame: Through study completion (~50 day)
Pharmacodynamic assessment - Thrombin generation
Thrombin generation (lag time, peak generation, Endogenous thrombin generation potential \[ETP\])
Time frame: Through study completion (~50 day)
Pharmacodynamic assessment - Pro-coagulant effect
Pro-coagulant effect (D-dimer, Fibrinogen, prothrombin fragments 1+2)
Time frame: Through study completion (~50 day)
Physical examination
Physical examination
Time frame: Through study completion (~50 day)
Incidence of participant abnormalities in 12-lead ECG (Ventricular rate in beat/min, Interval for PR in msec, QRS in msec, QTc in msec) for physiological parameter
The result for 12-lead ECG will be reported as Clinical Significant or Not-Clinical Significant. * Ventricular rate in beat/min * Interval for PR in msec * QRS in msec * QTc in msec
Time frame: Through study completion (~50 day)
Vital signs - blood pressure (Systolic, Diastolic)
Vital signs - blood pressure (Systolic, Diastolic)
Time frame: Through study completion (~50 day)
Vital signs - pulse rate
Vital signs - pulse rate
Time frame: Through study completion (~50 day)
Vital signs - body temperature
Vital signs - body temperature
Time frame: Through study completion (~50 day)
Frequency of Bleeding (only for hemophilia patients)
Bleeding evaluation (only for hemophilia patients) by questionnaire; Occurrence date, Persistence in yes or no questionnaire, Causes (blood in naturally occurring/Traumatic bleeding), Severity (mild/moderate/Severe)
Time frame: Through study completion (~50 day)
Local reaction in injection site
Pain or tenderness, itching, rash, redness (in mm), and induration (in mm) will be reported. Local stimulation test in injection site: Occurrence date, Persistence, Causes, Severity (mild/moderate/Severe) The occurrence of pain or tenderness, itching and rash will be reported by Yes or No questionnaire. The size of redness and induration will be measured in millmeters(mm).
Time frame: Through study completion (~50 day)
Incidence of participant abnormalities in laboratory tests by physiological parameter (Hematology, clinical chemistry, urinalysis, and blood coagulation test)
Parameters for laboratory tests include Hematology(WBC in 10\*\*3/mcL,Neutrophils in %,ANC in mcL,Lymphosyte in %,Monocyte in %,Eosinophils in %,Basophils in %,RBC in 10\*\*6/mcL,Hemoglobin in g/dL,Hematocrit in %,MCV in fL, MCH in pg,MCHC in g/dL,Platelets in 10\*\*3/mcL,MPV in fL),Clinical chemistry(Glucose in mg/dL,BUN in mg/dL,Uric adic in mg/dL,Total cholesterol in mg/dL,Triglyceride in mg/dL,Protein,Albumin in g/dL,Total bilirubin in mg/dL,Alkaline phosphatase in IU/L,AST in IU/L,ALT in IU/L,r-GT in IU/L,LDH in IU/L,Serum creatinine in mg/dL,Na in mmol/L,K in mmol/L,Cl in mmol/L,CPK in IU/L,Troponin I in ng/mL,Troponin T in ng/mL,Creatinine Clearance),Urinalysis(These values are reported only as a number;Specific garavity,Color,pH,Protein,Glucose,Ketone,Bilirubin,Blood,Urobilinogen,Nitrite,WBC,Squma EP cell,Casts,Crystal,Clarity,RBC),Blood coagulation test (aPTT in sec,PT in sec,Fibronogen in mg/dL,Antithrombon III in %,Protein C in %,Protein S in%)
Time frame: Through study completion (~50 day)