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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | GX-I7 SC 20㎍/㎏ (8 subjects) / Placebo (2 subjects) |
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| Cohort 2 | Experimental | GX-I7 SC 60㎍/㎏ (8 subjects) / Placebo (2 subjects) |
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| Cohort 3 | Experimental | GX-I7 IM 60㎍/㎏ (8 subjects) / Placebo (2 subjects) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GX-I7 | Drug | 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. |
| 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 |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory PD (PD) assessment: Change of the ratio of immune cells | Change of the ratio of immune cells by flow cytometer | 4 weeks |
| Exploratory PD (PD) assessment: T cells in lymphocytes by flow cytometer |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Howard Lee, M.D, Ph.D. | Seoul National University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Hospital | Seoul | 110-744 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26656713 | Background | Kang MC, Choi DH, Choi YW, Park SJ, Namkoong H, Park KS, Ahn SS, Surh CD, Yoon SW, Kim DJ, Choi JA, Park Y, Sung YC, Lee SW. Intranasal Introduction of Fc-Fused Interleukin-7 Provides Long-Lasting Prophylaxis against Lethal Influenza Virus Infection. J Virol. 2015 Dec 9;90(5):2273-84. doi: 10.1128/JVI.02768-15. | |
| 24899182 | Background |
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| ID | Term |
|---|---|
| C000712767 | efineptakin alfa |
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| Placebo | Drug | This is the placebo of GX-I7 described above. |
|
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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 |
Cluster of Differentiation 4 (CD4) T and Cluster of differentiation 8 (CD8) T in lymphocytes by flow cytometer
| 4 weeks |
| Seo YB, Im SJ, Namkoong H, Kim SW, Choi YW, Kang MC, Lim HS, Jin HT, Yang SH, Cho ML, Kim YM, Lee SW, Choi YK, Surh CD, Sung YC. Crucial roles of interleukin-7 in the development of T follicular helper cells and in the induction of humoral immunity. J Virol. 2014 Aug;88(16):8998-9009. doi: 10.1128/JVI.00534-14. Epub 2014 Jun 4. |
| 23624092 | Background | Ahn SS, Jeon BY, Park SJ, Choi DH, Ku SH, Cho SN, Sung YC. Nonlytic Fc-fused IL-7 synergizes with Mtb32 DNA vaccine to enhance antigen-specific T cell responses in a therapeutic model of tuberculosis. Vaccine. 2013 Jun 12;31(27):2884-90. doi: 10.1016/j.vaccine.2013.04.029. Epub 2013 Apr 23. |
| 23610371 | Background | Martin CE, van Leeuwen EM, Im SJ, Roopenian DC, Sung YC, Surh CD. IL-7/anti-IL-7 mAb complexes augment cytokine potency in mice through association with IgG-Fc and by competition with IL-7R. Blood. 2013 May 30;121(22):4484-92. doi: 10.1182/blood-2012-08-449215. Epub 2013 Apr 22. |
| 19950168 | Background | Nam HJ, Song MY, Choi DH, Yang SH, Jin HT, Sung YC. Marked enhancement of antigen-specific T-cell responses by IL-7-fused nonlytic, but not lytic, Fc as a genetic adjuvant. Eur J Immunol. 2010 Feb;40(2):351-8. doi: 10.1002/eji.200939271. |
| 21286380 | Background | Park SH, Song MY, Nam HJ, Im SJ, Sung YC. Codelivery of IL-7 Augments Multigenic HCV DNA Vaccine-induced Antibody as well as Broad T Cell Responses in Cynomolgus Monkeys. Immune Netw. 2010 Dec;10(6):198-205. doi: 10.4110/in.2010.10.6.198. Epub 2010 Dec 31. |
| 32339447 | Derived | Lee SW, Choi D, Heo M, Shin EC, Park SH, Kim SJ, Oh YK, Lee BH, Yang SH, Sung YC, Lee H. hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. Clin Transl Sci. 2020 Nov;13(6):1161-1169. doi: 10.1111/cts.12800. Epub 2020 May 20. |