Clinical Trial of GX-I7 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of GX-I7 in healthy volunteers.

Detailed Description
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The subjects who are adequately eligible to attend this clinical trial via screening will be hospitalized one day prior to the injection (Day -1), administered a single dose of GX-I7 solution for subcutaneous injection, and then discharged on Day 3. After completing all scheduled tests at the visit 8 (Day 28), safety-related data of each cohort will be evaluated by Independent Safety Monitoring Committee (SMC). Dose escalation will proceed under the principal investigator, medical monitor, and the sponsor's mutual approval, referring to SMC's evaluation.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GX-I7 in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: GX-I7
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is willing and able to give informed consent after listening character of the clinical trial Must be 19-45 years of age, inclusive Weight 50-100kg, BMI 18-30kg/m2 Subject who is adequately able to attend the study based on medical history and physical exam, no clinically significant abnormality from vital sign and clinical laboratory values No clinical abnormality from ECG test Non-smoker (no smoking or no use of any product containing nicotine least for one month and negative from urine test) Exclusion Criteria: Suspected or confirmed malignancy, or has malignancy history Any clinically significant acute or chronic medical condition requiring care of a physician, in liver, biliary tract, renal, nervous system (CNS or peripheral). respiratory system, endocrine (diabetes, hyperlipidemia etc), cardiovascular (congestive heart failure, coronary artery disease, myocardial infarction etc), hematology, malignancy, urinary disease, mental disorder, musculoskeletal disorder, immune system (rheumatoid arthritis, lupus etc), otorhinolaryngologic diseases Positive to HBsAg, hepatitis C virus (HCV) Ab and HIV Ab Are considering or scheduled to undergo any surgical or dental procedure during the study Administered other Investigational Product (IP) by attending other clinical study or biological equivalent study within recent 3 months Any Serious adverse drug reaction (SAR) against vaccines or antibiotics, any medical history with serious allergic diseases Positive from urine drug screen or respiratory alcohol screen at medical screening or check-in History of alcohol, drug, or substance abuse in the past 12 months Consumption of alcohol within 48 hours prior to hospitalization Medications with antacid, analgesic, herbal treatment, vitamin, mineral (except maximum 4 grams of acetaminophen) hormone, steroids, insulin, hypoglycemic drug or other hormone substitute within 14 days before administration Planning pregnancy or donation of sperm/disagreeing proper contraception during the study and 3 months following IP administration Do not have veins suitable for cannulation or multiple venipunctures Any other factor that the Investigator thinks will increase subject risk with participation

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>GX-I7 SC 20㎍/㎏ (8 subjects) / Placebo (2 subjects) | Drug: GX-I7<br>* Interleukin-7 (IL-7) is T cell growth factor that can be used for treating lymphopenia patients. GX-I7 is a protein drug recombining human IL-7 and hybrid Fc (hyFc). HyFc made by Genexine is composed of hinge-CH2 region of Immunoglobulin D (IgD) and CH2-CH3 region of Immunoglobulin G4 (IgG4). The recombined region is not exposed and each region's characteristics can reduce immunogenicity and improve the efficacy of drug. Consequently, it will be able to treat the patients with lymphopenia in effective ways.<br>* Other names: IL-7-hyFc;Drug: Placebo<br>* This is the placebo of GX-I7 described above.<br>* Other names: GX-17 vehicle (formulation buffer);|
| Experimental: Cohort 2<br>GX-I7 SC 60㎍/㎏ (8 subjects) / Placebo (2 subjects) | Drug: GX-I7<br>* Interleukin-7 (IL-7) is T cell growth factor that can be used for treating lymphopenia patients. GX-I7 is a protein drug recombining human IL-7 and hybrid Fc (hyFc). HyFc made by Genexine is composed of hinge-CH2 region of Immunoglobulin D (IgD) and CH2-CH3 region of Immunoglobulin G4 (IgG4). The recombined region is not exposed and each region's characteristics can reduce immunogenicity and improve the efficacy of drug. Consequently, it will be able to treat the patients with lymphopenia in effective ways.<br>* Other names: IL-7-hyFc;Drug: Placebo<br>* This is the placebo of GX-I7 described above.<br>* Other names: GX-17 vehicle (formulation buffer);|
| Experimental: Cohort 3<br>GX-I7 IM 60㎍/㎏ (8 subjects) / Placebo (2 subjects) | Drug: GX-I7<br>* Interleukin-7 (IL-7) is T cell growth factor that can be used for treating lymphopenia patients. GX-I7 is a protein drug recombining human IL-7 and hybrid Fc (hyFc). HyFc made by Genexine is composed of hinge-CH2 region of Immunoglobulin D (IgD) and CH2-CH3 region of Immunoglobulin G4 (IgG4). The recombined region is not exposed and each region's characteristics can reduce immunogenicity and improve the efficacy of drug. Consequently, it will be able to treat the patients with lymphopenia in effective ways.<br>* Other names: IL-7-hyFc;Drug: Placebo<br>* This is the placebo of GX-I7 described above.<br>* Other names: GX-17 vehicle (formulation buffer);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events including laboratory abnormality after Single Subcutaneous (SC) Injection of GX-I7 | Adverse events after injections. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Assessment: Maximum serum concentration (Cmax) | PK Parameters to be assessed by single SC administration will be Cmax. | 4 weeks | 
| Pharmacokinetic (PK) Assessment: Time to Cmax (Tmax) | PK Parameters to be assessed by single SC administration will be Tmax. | 4 weeks | 
| Pharmacokinetic (PK) Assessment: apparent terminal half-life (t1/2) | PK Parameters to be assessed by single SC administration will be t1/2. t1/2=lnf(2)/λz (λz: invariable for speed of loss obtained from linear regression analysis in logarithmic plot of terminal phase) | 4 weeks | 
| Pharmacokinetic (PK) Assessment: Area under the curve from zero to last time of measurable concentration after single administration by trapezoidal rule (AUCt) | PK Parameters to be assessed by single SC administration will be AUC (0-inf). | 4 weeks | 
| Pharmacokinetic (PK) Assessment: Area under the curve from zero to infinity (AUC(0-inf)) | PK Parameters to be assessed by single SC administration will be AUC(0-inf). | 4 weeks | 
| Pharmacodynamic (PD) Assessment: Emax of Absolute Lymphocyte Count (ALC) | PD parameters will be determined by Emax of ALC, which will be compared with peripheral baseline. | 8 weeks | 
| Pharmacodynamic (PD) Assessment: Area Under The Effect-Time Curve Up To Last Quantifiable Effect (AUEClast) of ALC | PD parameters will be determined by AUEClast of ALC, which will be compared with peripheral baseline. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Pharmacodynamics, Dose-Limiting Toxicity (DLT), Immunogenicity, Pharmacokinetics