The purpose of this study is to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of subcutaneous MG1113 in the multiple ascending dose study in patients with severe hemophilia.
This is a repeat-dose study that assign 5 subjects in each cohort to explore the safety, tolerability, PK, and PD of the study drug by sequentially increasing the study drug. The route of administration is subcutaneous (SC) injection. Dose escalation will be decided 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 Steering Committee and Data and Safety Monitoring Boards (DSMB) in the evaluation of the safety and tolerability data obtained from each cohort after repeated administration of MG1113. The subjects will be treated with 2.0 mg/kg once weekly for 8 weeks in cohort 1. Visit window of ±1 day (calculated from Day1) are allowed for the dosing schedule after first IP administration (Day 1). But next scheduled IP administration must be kept in mind to ensure subjects will not have more than 8 days in between IP dosing interval. The next dose level (Dose A and B) will be determined based on the safety, PK, and PD data obtained from previous dose level. If a criterion of discontinuation of dose escalation is fulfilled, discussion about dose escalation is available for next cohort. The dose selection and escalation will be finally determined from the Steering Committee and DSMB. The safety, tolerability, PK, and PD data obtained from all subjects up to Cohort 3 will be evaluated by the Steering Committee and Data and Safety Monitoring Boards (DSMB).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
MG1113 subcutaneous (SC) injection
GC Biopharma Corp.
Yongin-si, Gyeonggi-do, South Korea
Number of subject with Adverse events, Adverse Drug Reactions, Serious adverse events and Adverse event of special interest (AESI)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Incidence of Adverse events, Adverse Drug Reactions, Serious adverse events and Adverse event of special interest (AESI)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Severity of Adverse events, Adverse Drug Reactions, Serious adverse events and Adverse event of special interest (AESI)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Incidence of injection site reaction
Time frame: Study Day 1 to Day 57 visit
Severity of injection site reaction
Time frame: Study Day 1 to Day 57 visit
Number of subjects with abnormal Physical examination
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Number of subjects with abnormal 12-lead ECG (Ventricular rate in beat/min, Interval for PR in msec, QRS in msec, QTc in msec)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Number of subjects with abnormal Vital signs (Blood pressure in mmHg, Pulse rate in beats/min, Respiration rate in breaths/min, Body temperature in ℃)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Incidence of clinically significant laboratory value abnormalities
Time frame: Through study completion (Study Day 1 to Day 78 visit)
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Pharmacokinetic assessment - Cmax (Peak plasma concentration)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - Cmin (Minimum plasma concentration)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - AUC (Area under the plasma concentration versus time curve)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - Tmax (Time to maximum plasma concentration after administration)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - half-life (T1/2; the time required to reduce the plasma concentration by half)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - CL/F (apparent clearance)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - Vd/F (apparent volume of distribution)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacokinetic assessment - Accumulation Index (AUCtau_multiple dose/AUCtau_single dose)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Free TFPI in plasma in ng/mL
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Residual TFPI activity in unit/mL
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Diluted PT in sec
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Thrombin generation (Lag time in min)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Thrombin generation (Peak generation in nM)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Thrombin generation (Endogenous thrombin generation potential [ETP] in nM*min)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Pro-coagulant effect (D-dimer in ug/mL)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Pro-coagulant effect (Fibrinogen in mg/dL)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Pharmacodynamic assessment - Pro-coagulant effect (Prothrombin fragments 1+2 in pmol/L)
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Immunogenicity assessment - Any formation of anti-drug antibody (ADA) to MG1113
Time frame: Through study completion (Study Day 1 to Day 78 visit)
Efficacy Evaluation - Incidence of new bleeding episode
Time frame: Study Day 1 to Day 57 visit