Phase I Study GX-G3 in Healthy Subjects

Study Overview
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Brief Summary
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pharmacokinetics/pharmacodynamics of GX-G3 after single subcutaneous administration in healthy male subjects.

Detailed Description
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MTD will be determined by DLT occurrence and frequency, and severity and charactoristic of adverse event, vital sign, physical examination, ECG, Laboratory test, chest-X-ray will be examined for safety evaluation. The second purpose is to evaluate pharmacokinetics and pharmacodynamics, and immunogenecity will be evaluated to investigate antibody production.

Official Title
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A Dose-block Randomized, Double-blind, Placebo-controlled, Dose-escalation Phase I Study to Investigate the Safety, Tolerability, and PK/PD of GX-G3 After Single SC Administration in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: GX-G3 12.5 μg/kg or Placebo
* Drug: GX-G3 25 μg/kg or Placebo
* Drug: GX-G3 50 μg/kg or Placebo
* Drug: GX-G3 100 μg/kg or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects may be entered in the study only if they meet all of the following criteria: Are capable of understanding and complying with the requirements of the study and have voluntarily signed the informed consent form (ICF); Healthy male volunteers aged 20-45 years; Have a body weight of 60-90 kg (inclusive), have a body mass index (BMI) equal to or greater than 19 and less than 27 kg/m2; Are eligible for the study based on screening data (Subjects may participate if Investigator considered eligible after looking at other screening data); Exclusion Criteria: Subjects presenting with any of the following will not be entered in to the study: Have a history of or current evidence of disease; Have percent of white blood cell (WBC) or neutrophil > UNL; Have count of platelet < 100,000/mm3; Have the longest length of spleen > 16 cm measured by abdomen ultrasonography ; Have MSSBP ≥ 140 mmHg or ≤ 90 mmHg and/or MSDBP ≥ 95 mmHg or ≤ 50 mmHg; (BP must be measured after resting for at least 3 minutes) Have clinically significant arrhythmia by EKG/ECG; Are positive for HBV, HCV, HIV; Have a history of allergy/hypersensitivity or ongoing allergy/hypersensitivity to any drug, as judged by the investigator; Have had any blood donation/ blood loss greater than 400 ml within 8 weeks prior to dosing; Have participated in another clinical trial with investigational drugs within 8 weeks of screening period; Any other conditions that are considered inappropriate or unsafe for subjects by the Investigator; Are considered ineligible by the investigator due to physical findings or laboratory values at the screening assessments; Have a history of G-CSF treatment;

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>GX-G3 12.5 μg/kg or Placebo | Drug: GX-G3 12.5 μg/kg or Placebo<br>* Single SC injection<br>* Other names: GX-G3(G-CSF-hyFc);|
| Experimental: Cohort 2<br>GX-G3 25 μg/kg or Placebo | Drug: GX-G3 25 μg/kg or Placebo<br>* Single SC injection<br>* Other names: GX-G3(G-CSF-hyFc);|
| Experimental: Cohort 3<br>GX-G3 50 μg/kg or Placebo | Drug: GX-G3 50 μg/kg or Placebo<br>* Single SC injection<br>* Other names: GX-G3(G-CSF-hyFc);|
| Experimental: Cohort 4<br>GX-G3 100 μg/kg or Placebo | Drug: GX-G3 100 μg/kg or Placebo<br>* Single SC injection<br>* Other names: GX-G3(G-CSF-hyFc);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT incidence and frequency after GX-G3 single S.C. injection | [DLT criteria: CTCAE V4.03] Hematologic type: grade 3 Hematologic N.O.S, grade 3 or 4 Leukocytosis Non-Hematologic: grade 3 N.O.S N.O.S: not otherwise specified Leukocytosis: continued more than 5 days, grade 3(>100,000 cells/mm3), or grade 4(clinical manifestations of leucostasis; urgent intervention indicated) | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events incidence and frequency at each dose group after GX-G3 single injection |  | 6 weeks | 
| Pharmacokinetics parameters after GX-G3 single injection | AUC/D, Cmax/D, AUC, AUClast, Cmax, tmax, half-life | 3 weeks | 
| Pharmacodynamics parameters after GX-G3 single injection | Emax, Emax, Tmax and AUEClast of absolute neutrophil count(ANC), WBC count and CD34+ cell count | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Pharmacokinetics, Pharmacodynamics, DLT, Immunogenecity