A Clinical Trial to Evaluate Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Characteristics of KMRC011

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

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

Study Overview

• Status: Completed
• Conditions: Acute Radiation Syndrome
• Intervention / Treatment: Drug: KMRC011 5μg or Placebo; Drug: KMRC011 10μg or Placebo; Drug: KMRC011 15μg or Placebo; Drug: KMRC011 20μg or Placebo; Drug: KMRC011 25μg or Placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 06351
      • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: KMRC011 5μg or Placebo; Cohort 1	Drug: KMRC011 5μg or Placebo; Intramuscular Injection of KMRC011 5μg or Placebo(Normal Saline) 0.1ml; Other Names: Cohort 1
Other: KMRC011 10μg or Placebo; Cohort 2	Drug: KMRC011 10μg or Placebo; Intramuscular Injection of KMRC011 10μg or Placebo(Normal Saline) 0.2ml; Other Names: Cohort 2
Other: KMRC011 15μg or Placebo; Cohort 3	Drug: KMRC011 15μg or Placebo; Intramuscular Injection of KMRC011 15μg or Placebo(Normal Saline) 0.3ml; Other Names: Cohort 3
Other: KMRC011 20μg or Placebo; Cohort 4	Drug: KMRC011 20μg or Placebo; Intramuscular Injection of KMRC011 30μg or Placebo(Normal Saline) 0.4ml; Other Names: Cohort 4
Other: KMRC011 25μg or Placebo; Cohort 5	Drug: KMRC011 25μg or Placebo; Intramuscular Injection of KMRC011 45μg or Placebo(Normal Saline) 0.5ml; Other Names: Cohort 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with treatment-emergent adverse event or adverse drug reaction	Up to 7±1 days after injection
Number of subjects with clinically significant changes in hematology test result after injection	Up to 7±1 days after injection
Number of subjects with clinically significant changes in blood chemistry test result after injection	Up to 7±1 days after injection
Number of subjects with clinically significant changes in urinalysis test result after injection	Up to 7±1 days after injection
Number of subjects with clinically significant changes in blood coagulation test result after injection	Up to 7±1 days after injection
Number of subjects with clinically significant changes in ECG (Electrocardiogram) after injection	Up to 7±1 days after injection
Number of subjects with clinically significant changes in vital sign after injection	Up to 7±1 days after injection
Number of subjects with clinically significant physical abnormality after injection	Up to 7±1 days after injection
Maximum serum concentration (Cmax) of KMRC011	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
Time of the maximum serum concentration (Tmax) of KMRC011	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
Area under the serum concentration versus time curve, from time 0 to the last measurable concentration (AUC0-t) of KMRC011	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
Area under the serum concentration versus time curve from time 0 to infinity (AUCinf) of KMRC011	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
Percentage of AUCinf due to extrapolation from time of last measurable concentration to infinity (AUCextra) of KMRC011	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
Apparent clearance (CL/F) of KMRC011	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
Apparent volume of distribution (Vd/F) of KMRC011	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
Terminal half-life (t1/2) of KMRC011	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
Maximum effect over the time span specified (Emax) of G-CSF	Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
Maximum effect over the time span specified (Emax) of IL-6	Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
Area under the effect versus time curve, from time 0 to the last measurable concentration (AUEC0-t) of G-CSF	Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose
Area under the effect versus time curve, from time 0 to the last measurable concentration (AUEC0-t) of IL-6	Pre-dose(0 hours) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of KMRC011	A dose that is one level lower than the dose which Dose Limiting Toxicity (DLT) incidence is 33% or more is determined as a Maximum Tolerated Dose (MTD). If the Dose Limiting Toxicity (DLT) incidence is lower than 33% at all doses level, we conclude Maximum Tolerated Dose (MTD) cannot be determined.	Until the study completion, approximately up to 35 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Number of subjects who expressed Anti-Drug (KMRC011) Antibody (ADA)	Up to 28±2 days after injection

Collaborators and Investigators

• Sponsor: Intron Biotechnology, Inc.
• Investigators: Principal Investigator: Jung-Ryul Kim, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): September 11, 2019
• Study Completion (Actual): November 28, 2019

Study Registration Dates

• First Submitted: June 3, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Radiation Injuries; Acute Radiation Syndrome
• Other Study ID Numbers: KMRC011-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No