Clinical trial NCT03585803: A Clinical Trial to Evaluate Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Characteristics of KMRC011
Official title: A Dose Blocked-Randomized, Single-Blind, Placebo-Controlled and Dose-Escalation Phase I Clinical Trial to Evaluate Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Characteristics of KMRC011 After Intramuscular Administration in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Radiation Syndrome
Lead sponsor: Intron Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-13
Enrollment: 26
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is designed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic of KMRC011 injection in healthy adult volunteers.


Eligibility criteria: Inclusion Criteria:

* A male whose age is between 19 and 55 years of age
* A person whose body mass index is between 18.5 and 27 kg/m2 at screening
* A person who has the ability and willingness to participate in the clinical trial
* A person who voluntarily agrees with the clinical trial after hearing and fully understanding the detailed explanation of this clinical trial

Exclusion Criteria:

* A person who has a clinically significant disease or history of liver, kidney, neuropsychiatry, immune system, respiratory system, endocrine system, hematology\*oncology system, cardiovascular system, etc.(In the case of liver disease items, it includes subjects who have hepatitis virus)
* A person who has clinical history of hypersensitivity reactions to the major components or constituents of investigational product or other clinically significant hypersensitivity reactions to drugs or foods, or those with allergic diseases requiring treatment
* A person with infectious disease or severe trauma within 21 days of the randomization date
* A person whose serum AST, ALT or γ-GT levels exceed 1.5 times the upper limit of the reference range at screening
* A person whose QTcF on the electrocardiogram exceeds 430 msec or who has a clinically significant abnormal rhythm at screening
* A person with a glomerular filtration rate less than 60 mL/min/1.73 m2 calculated from serum creatinine at screening
* A person with a systolic blood pressure less than 100 mmHg, greater than 150 mmHg, diastolic blood pressure less than 60 mmHg, or greater than 100 mmHg at screening
* A person with thrombocytopenia or coagulopathy which should not be given intramuscular injection
* A person whose weekly average drinking amount exceeds 140g of alcohol per week
* A person whose daily average smoking amount exceeds 10 per day
* A person who have received a drug that can significantly affect the absorption, distribution, metabolism or excretion of the investigational product within 14 days of the injection
* A person who has the history of substance abuse or positive urine screening test
* A person who have received a investigational product or a bioequivalence study drug within at least 90 days prior to the randomization
* A person who donated whole blood within 60 days before the randomization, or donated components of blood within 30 days
* A person who dose not have a medically approved contraceptive during the trial and has a plan to provide sperm
* A person who has clinically significant abnormalities from clinical laboratory test
* A person who is deemed ineligible for clinical trials by the investigator

Primary outcomes:
measure: Number of subjects with treatment-emergent adverse event or adverse drug reaction
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant changes in hematology test result after injection
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant changes in blood chemistry test result after injection
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant changes in urinalysis test result after injection
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant changes in blood coagulation test result after injection
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant changes in ECG (Electrocardiogram) after injection
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant changes in vital sign after injection
timeFrame: Up to 7±1 days after injection
measure: Number of subjects with clinically significant physical abnormality after injection
timeFrame: Up to 7±1 days after injection
measure: Maximum serum concentration (Cmax) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Time of the maximum serum concentration (Tmax) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Area under the serum concentration versus time curve, from time 0 to the last measurable concentration (AUC0-t) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Area under the serum concentration versus time curve from time 0 to infinity (AUCinf) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Percentage of AUCinf due to extrapolation from time of last measurable concentration to infinity (AUCextra) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Apparent clearance (CL/F) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Apparent volume of distribution (Vd/F) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Terminal half-life (t1/2) of KMRC011
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post-dose
measure: Maximum effect over the time span specified (Emax) of G-CSF
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
measure: Maximum effect over the time span specified (Emax) of IL-6
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
measure: Area under the effect versus time curve, from time 0 to the last measurable concentration (AUEC0-t) of G-CSF
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
measure: Area under the effect versus time curve, from time 0 to the last measurable concentration (AUEC0-t) of IL-6
timeFrame: Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
Secondary outcomes:
measure: Maximum Tolerated Dose (MTD) of KMRC011
timeFrame: Until the study completion, approximately up to 35 weeks
Other outcomes:
measure: Number of subjects who expressed Anti-Drug (KMRC011) Antibody (ADA)
timeFrame: Up to 28±2 days after injection
Locations:
city: Gangnam-gu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
Study officials:
affiliation: Samsung Medical Center
name: Jung-Ryul Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: