Clinical trial NCT02860715: Clinical Trial of GX-I7 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Safety
Pharmacodynamics
Dose-Limiting Toxicity (DLT)
Immunogenicity
Pharmacokinetics
Lead sponsor: Genexine, Inc.
Sponsor class: INDUSTRY
First posted: 2016-08-09
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Subject is willing and able to give informed consent after listening character of the clinical trial
2. Must be 19-45 years of age, inclusive
3. Weight 50-100kg, BMI 18-30kg/m2
4. 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
5. No clinical abnormality from ECG test
6. Non-smoker (no smoking or no use of any product containing nicotine least for one month and negative from urine test)

Exclusion Criteria:

1. Suspected or confirmed malignancy, or has malignancy history
2. 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
3. Positive to HBsAg, hepatitis C virus (HCV) Ab and HIV Ab
4. Are considering or scheduled to undergo any surgical or dental procedure during the study
5. Administered other Investigational Product (IP) by attending other clinical study or biological equivalent study within recent 3 months
6. Any Serious adverse drug reaction (SAR) against vaccines or antibiotics, any medical history with serious allergic diseases
7. Positive from urine drug screen or respiratory alcohol screen at medical screening or check-in
8. History of alcohol, drug, or substance abuse in the past 12 months
9. Consumption of alcohol within 48 hours prior to hospitalization
10. 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
11. Planning pregnancy or donation of sperm/disagreeing proper contraception during the study and 3 months following IP administration
12. Do not have veins suitable for cannulation or multiple venipunctures
13. Any other factor that the Investigator thinks will increase subject risk with participation

Primary outcomes:
measure: Assessment of adverse events including laboratory abnormality after Single Subcutaneous (SC) Injection of GX-I7
timeFrame: 4 weeks
Secondary outcomes:
measure: Pharmacokinetic (PK) Assessment: Maximum serum concentration (Cmax)
timeFrame: 4 weeks
measure: Pharmacokinetic (PK) Assessment: Time to Cmax (Tmax)
timeFrame: 4 weeks
measure: Pharmacokinetic (PK) Assessment: apparent terminal half-life (t1/2)
timeFrame: 4 weeks
measure: Pharmacokinetic (PK) Assessment: Area under the curve from zero to last time of measurable concentration after single administration by trapezoidal rule (AUCt)
timeFrame: 4 weeks
measure: Pharmacokinetic (PK) Assessment: Area under the curve from zero to infinity (AUC(0-inf))
timeFrame: 4 weeks
measure: Pharmacodynamic (PD) Assessment: Emax of Absolute Lymphocyte Count (ALC)
timeFrame: 8 weeks
measure: Pharmacodynamic (PD) Assessment: Area Under The Effect-Time Curve Up To Last Quantifiable Effect (AUEClast) of ALC
timeFrame: 8 weeks
Other outcomes:
measure: Exploratory PD (PD) assessment: Change of the ratio of immune cells
timeFrame: 4 weeks
measure: Exploratory PD (PD) assessment: T cells in lymphocytes by flow cytometer
timeFrame: 4 weeks
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Howard Lee, M.D, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.