Status Approved
First Submitted Date
2020/05/07
Registered Date
2020/07/28
Last Updated Date
2020/11/06
CRIS Required
WHO ICTRP (International Clinical Trial Registry Platform) Required
1. Background
CRIS Registration Number |
KCT0005257 |
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Unique Protocol ID | H-1903-057-1017 |
Public/Brief Title | A dose-block randomized, double-blind, placebo-controlled, single dosing, dose-escalation phase I clinical trial to investigate the safety/tolerability and pharmacokinetics of HNP-2006 after intravenous administration in healthy adult volunteers |
Scientific Title | A dose-block randomized, double-blind, placebo-controlled, single dosing, dose-escalation phase I clinical trial to investigate the safety/tolerability and pharmacokinetics of HNP-2006 after intravenous administration in healthy adult volunteers |
Acronym | |
MFDS Regulated Study | Yes |
IND/IDE Protocol | Yes |
Registered at Other Registry | No |
Healthcare Benefit Approval Status | Not applicable |
2. Institutional Review Board / Ethics Committee
Board Approval Status | Submitted approval |
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Board Approval Number | H-1903-057-1017 |
Approval Date | 2019-03-27 |
Institutional Review Board Name | Seoul National University Hospital Institutional Review Board |
Institutional Review Board Address | 101, Daehak-ro, Jongno-gu, Seoul |
Institutional Review Board Telephone | 02-2072-0694 |
Data Monitoring Committee | No |
3. Contact Details
Contact Person for Principal Investigator / Scientific Queries | |
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Name | SeungHwan Lee |
Title | Associate Professor |
Telephone | +82-2-2072-2343 |
Affiliation | Seoul National University Hospital |
Address | 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea |
Contact Person for Public Queries | |
Name | KiYoung Huh |
Title | Resident |
Telephone | +82-2-2072-1666 |
Affiliation | Seoul National University Hospital |
Address | 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea |
Contact Person for Updating Information | |
Name | MinAh Choi |
Title | Study Manager |
Telephone | +82-2-559-5780 |
Affiliation | Hana Pharm |
Address | 10F, EK tower, 407 Teheran-ro, Gangnam-gu, Seoul, Republic of Korea |
4. Status
Study Site | Single | |
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Overall Recruitment Status | Completed | |
Date of First Enrollment | 2020-01-13 Actual | |
Target Number of Participant | 40 | |
Primary Completion Date | 2020-08-18 , Actual | |
Study Completion Date | 2020-09-15 , Actual | |
Recruitment Status by Participating Study Site 1 | ||
Name of Study | Seoul National University Hospital | |
Recruitment Status | Completed | |
Date of First Enrollment | 2020-01-13 , |
5. Source of Monetary / Material Support
1. Source of Monetary/Material Support | |
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Organization Name | Hana Pharm |
Organization Type | Pharmaceutical Company |
Project ID | HNP-2006-CS-101 |
6. Sponsor Organization
1. Sponsor Organization | |
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Organization Name | Hana Pharm |
Organization Type | Pharmaceutical Company |
7. Study Summary
Lay Summary | 1) Purpose This study aims to evaluate the safety, tolerability and pharmacokinetics of HNP-2006 after a single intravenous administration in healthy adults. 2) Backgroud Contrast agent is a drug injected into a human body to make a specific organ, tissue, or blood vessel look clear by improving contrast of structures in the body and body fluids during diagnostic imaging, including radiography, ultrasonography, and magnetic resonance imaging (MRI), or procedures. Use of contrast agent is a noninvasive and innovative way to diagnose a disease, but long-term, potential results of use of contrast agent can never be ignored. MRI contrast agent is classified into positive and negative, or T1 and T2 contrast agent, and the disadvantage of contrast agent is that a broader area than an actual area is exposed for imaging. In Korea, T2 contrast agent (Feridex and Resovist) were marketed, but the marketing has been stopped due to inconvenience and side effects experienced by patients (The most common side effects was low back pain and the incidence of side effects was approximately 10 - 15 %). The most commonly used T1 contrast agent in clinical settings is Gd-DOTA and Gd-DO3A. Gadolinium contrast agent is mostly removed through a kidney, but trace amounts of gadolinium may remain in the body, bones, skin, and organs, and it is known that more gadolinium remains when a linear agent rather than a macrocyclic agent is used. In this regard, nephrogenic systemic fibrosis, a disease where fibrosis is caused when gadolinium ion (Gd3+) is separated, may occur as a serious side effect. In 2010, the US Food and Drug Administration (FDA) recommended that gadodiamide and gadopentetate should not be used in patients with severe renal impairment (eGFR < 30mL/min/1.73m2), and Korea also distributed a safety letter. In addition, in 2017, the European Commission announced withdrawal of marketing approval for drugs containing any of the three components (gadodiamide, gadopentetate meglumine, and gadoversetamide) of linear gadolinium contrast agents as a result of reviewing benefit-risk of accumulation of gadolinium in the brain. In August 2018, Korea also announced that approval and supply were maintained only for gadoterate, gadoteridol, and gadobutrol and that supply of drugs containing any of gadodiamide, gadopentetate meglumine, or gadoversetamide would be gradually discontinued by the end of 2018. As shown above, safety of contrast agent is a continuously discussed issue, and development of an alternative drug that is safer than existing contrast agents is required. Therefore, to resolve safety issues related to release of gadolinium ion, a new drug <HNP-2006> has been developed as a contrast agent that has high water solubility, ensures safety by reducing toxicity compared to existing MRI contrast agents, and shows great contrast enhancement. HNP-2006 is a new functional cyclic contrast agent that has high water solubility by using ligand DO3A- acetamide and shows a higher relaxation rate and thermodynamic and pharmacokinetic stability compared to existing gadolinium. This study aims to evaluate the safety, tolerability and pharmacokinetics of HNP-2006 after a single intravenous administration in healthy adults. 3) Design A dose-block randomized, double-blind, placebo-controlled, single dosing, dose-escalation phase I clinical trial This study will sequentially increase the dose from the lowest dose for Cohort 1 (0.02 mmol/kg). Upon the completion of each cohort, the investigator and sponsor will review blinded safety data and if necessary, PK data obtained, and determine whether to proceed to the subsequent cohort. When determining whether to proceed from Cohort 3 (0.1 mmol/kg) to Cohort 4 (0.2 mmol/kg), 2 independent experts (1 clinical pharmacologist and 1 radiologist) will review blinded data prior to a decision on dose escalation. |
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8. Study Design
Study Type | Interventional Study |
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Study Purpose | Treatment |
Phase | Phase1 |
Intervention Model | Parallel |
Blinding/Masking | Double |
Blinded Subject | Subject, Investigator |
Allocation | RCT |
Intervention Type | Drug |
Intervention Description | A dose-block randomized, single dosing, intravenous administration 1) 1Cohort: 0.02mmol/kg HNP-2006(6) or placebo(2) 2) 2Cohort: 0.05mmol/kg HNP-2006(6) or placebo(2) 3) 3Cohort: 0.10mmol/kg HNP-2006(6) or placebo(2) 4) 4Cohort: 0.20mmol/kg HNP-2006(6) or placebo(2) 5) 5Cohort: 0.30mmol/kg HNP-2006(6) or placebo(2) |
Number of Arms | 2 |
Arm 1 |
Arm Label HNP-2006 |
Target Number of Participant 30 |
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Arm Type Experimental |
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Arm Description A dose-block randomized, single dosing, intravenous administration 1) 1Cohort: 0.02mmol/kg HNP-2006(6) 2) 2Cohort: 0.05mmol/kg HNP-2006(6) 3) 3Cohort: 0.10mmol/kg HNP-2006(6) 4) 4Cohort: 0.20mmol/kg HNP-2006(6) 5) 5Cohort: 0.30mmol/kg HNP-2006(6) |
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Arm 2 |
Arm Label Placebo of HNP-2006 injection |
Target Number of Participant 10 |
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Arm Type Placebo comparator |
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Arm Description A dose-block randomized, single dosing, intravenous administration 1) 1Cohort: 0.04ml/kg placebo(2) 2) 2Cohort: 0.10ml/kg placebo(2) 3) 3Cohort: 0.20ml/kg placebo(2) 4) 4Cohort: 0.40ml/kg placebo(2) 5) 5Cohort: 0.60ml/kg placebo(2) |
9. Subject Eligibility
Condition(s)/Problem(s) |
Not Applicable-Etc
Healthy adult/Contrast Media [D27.505.259.500] |
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Rare Disease | No |
Inclusion Criteria |
Gender Both |
Age 19Year~55Year |
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Description 1.Healthy adults aged ≥ 19 to < 55 years at the time of screening test 2.Body mass index (BMI) of ≥ 18.5 to < 27.0 ※ BMI = Body weight (kg)/[height (m)2] 3.For females, one of the following must be met: - Menopause (no spontaneous menses for at least 2 years) - Surgical sterilization (being sterile by hysterectomy or bilateral oophorectomy, tubal ligation, or other methods) 4.For males who are sexually active with females of childbearing potential, agreed to use contraception (use of double barrier contraceptive methods such as condom with diaphragm or cervical cap) and not to donate sperm during the study period and for at least 8 weeks after the last dose of the investigational product (if male subjects or their female partners are infertile, the above contraceptive methods are not needed) 5.Voluntarily decided to participate in the study and provided written consent to follow precautions after receiving a sufficient explanation on this study and fully understanding the information |
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Exclusion Criteria |
1.Presence or history of clinically significant hepatobiliary (e.g., severe hepatic impairment), renal (e.g., acute or chronic severe renal impairment, acute renal failure due to hepatorenal syndrome, and acute renal failure before and after liver transplantation), nervous (e.g., spastic disorders such as epilepsy), immune, respiratory, endocrine, and cardiovascular (e.g., congenital long QT syndrome and heart failure) diseases, malignant tumor, or mental diseases 2.Family history of long QT syndrome or dysrhythmia after administration of a drug prolonging the repolarization cycle of action potential 3.Medical history of hypersensitivity to contrast agents or any components of contrast agents, bronchial asthma or allergy, and clinically significant hypersensitivity 4.Subjects who met any of the following in the screening test - AST, ALT in blood > 1.5 x the upper limit of normal - Total bilirubin in blood > 1.5 x the upper limit of normal - eGFR < 90 mL/min/1.73m2 based on CKD-EPI formula 5.Systolic blood pressure > 150 mmHg or < 90 mmHg or diastolic blood pressure > 100 mmHg or < 60 mmHg in the vital signs measured in the sitting position after at least 5 minutes rest. 6.Positive serologic test result (hepatitis B, hepatitis C, human immunodeficiency virus, and syphilis) 7.History of drug abuse or positive result in urine drug screening test 8.Gadolinium-based contrast agents (e.g., Gadovist and Dotarem) administered within 30 days prior to the administration of the investigational product 9.Use of any prescribed drugs or herbal medicines within 14 days, or any over-the-counter (OTC) drugs including dietary supplement and vitamins within 7 days prior to the administration of the investigational product, which is considered to affect this study or the safety of the subjects in the opinion of the investigator 10.Participated in another clinical study (including bioequivalence study) and received an investigational product within 90 days [6 months as of 12 Jun 2019] prior to the administration of this investigational product (The period may be extended for biological products considering a half-life) 11.Donated whole blood within 60 days, or donated blood components within 30 days prior to the administration of the investigational product 12.Received a blood transfusion within 30 days prior to the administration of the investigational product 13.Determined to be ineligible to participate in the study by the investigator due to other reasons |
Healthy Volunteers | Yes |
10. Outcome Measure(s)
Type of Primary Outcome | Pharmacokinetics | |
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Primary Outcome(s) 1 | ||
Outcome | AUClast, AUCinf, Cmax, Tmax, t1/2, CL, Vd, MRT of HNP-2006 |
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Timepoint | Before administration of investigational product, up to 72 hours |
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Secondary Outcome(s) 1 | ||
Outcome | Safety and tolerability evaluation (Adverse Events, Physical Examination, Vital Signs, Clinical Laboratory Test 12-lead ECG, etc.) |
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Timepoint | Up to 14 days |
11. Study Results and Publication
Result Registered | No |
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12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)
Sharing Statement | No |
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