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A Dose-Block Randomized, Placebo Controlled (Double-blind), Active Controlled(Open-label), Dose-escalation Study

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ClinicalTrials.gov Identifier: NCT02175056
Recruitment Status : Completed
First Posted : June 26, 2014
Last Update Posted : October 6, 2015
Sponsor:
Information provided by (Responsible Party):
Handok Pharmaceuticals Co., Ltd.

Brief Summary:
The study design of this trial is a Dose-Block Randomized, Placebo controlled (Double-blind), Active Controlled(Open-label), Dose-escalation.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Biological: HL2351 Biological: Kineret(Anakinra) Phase 1

Detailed Description:
  • Extended in vivo half-life of HL2351 is also anticipated to provide improved therapeutic efficacy based on sustained maintenance of an effective concentration.
  • A safety concern may be addressed by utilizing IL-1Ra that is being used after getting approval by the EMA and the US FDA and known to be relatively safe, and the Fc fusion technology that has been already applied to various therapeutic agents.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Dose-Block Randomized, Placebo Controlled (Double-blind), Active Controlled(Open-label), Dose-escalation Study to Investigate the Tolerability, and Pharmacokinetics/Pharmacodynamics of HL2351 After a Single Subcutaneous Administration in Healthy Male Subjects
Study Start Date : May 2014
Actual Primary Completion Date : January 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Anakinra

Arm Intervention/treatment
Experimental: HL2351
1, 2, 4, 8, 12 mg/kg (SC) / Single-Dose
Biological: HL2351
Dose-escalation For 5 level dose groups A ~ E(each 1, 2, 4, 8, 12mg/kg), 10 subjects (8 for the study drug and 2 for placebo) are randomized to each dose group, and the study drug or placebo is subcutaneously administered for the relevant dose group.

Placebo Comparator: Placebo
1, 2, 4, 8, 12 mg/kg (SC) / Single-Dose
Biological: HL2351
Dose-escalation For 5 level dose groups A ~ E(each 1, 2, 4, 8, 12mg/kg), 10 subjects (8 for the study drug and 2 for placebo) are randomized to each dose group, and the study drug or placebo is subcutaneously administered for the relevant dose group.

Active Comparator: Kineret(Anakinra)
100 mg (SC) / Single-Dose
Biological: Kineret(Anakinra)
Active comparator(group F) is implemented in parallel with dose groups A~E in an open-label manner and 8 subjects subcutaneously administer Kineret® 100 mg.




Primary Outcome Measures :
  1. Tolerability as measured by the occurrence of Adverse Events [ Time Frame: 29 days ]

    Adverse Events after single subcutaneous dose of HL2351

    : check Day -1, 1, 2, 3, 4, 5, 7, 11, 15, 22, 29


  2. Tolerability as measured by Physical Examination, Vital Signs and Safety Laboratory Tests [ Time Frame: 29 days ]
    Changes from baseline in physical examination, vital signs, ECG, clinical laboratory tests (routine hematology, routine chemistry, blood coagulation and urinalysis) after single subcutaneous dose of HL2351

  3. Tolerability as measured by the occurrence of Local Toxicity [ Time Frame: 4 days ]

    Local Toxicity after single subcutaneous dose of HL2351

    : check Day 1, 2, 4


  4. Tolerability as measured by Cytokine Laboratory Test [ Time Frame: 4 days ]

    Cytokine Laboratory Test after single subcutaneous dose of HL2351

    : check Day 1, 2, 4


  5. Pharmacokinetics of HL2351: Maximum plasma concentration(Cmax) [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  6. Pharmacokinetics of HL2351: Area under plasma drug concentration-time curve [AUC(0-last), AUCinf] [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  7. Pharmacokinetics of HL2351: Time of maximum concentration(Tmax) [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  8. Pharmacokinetics of HL2351: Elimination half-life(T1/2) [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  9. Pharmacokinetics of HL2351: Apparent Clearance(CL/F) [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  10. Pharmacokinetics of HL2351: Apparent Volume of Distribution(Vz/F) [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  11. Pharmacokinetics of HL2351: Mean Residence Time (MRT) [ Time Frame: 29 days ]
    To assess pharmacokinetics after single subcutaneous injection of HL2351

  12. Pharmacodynamics of HL2351: IL-6 inhibition assay [ Time Frame: 7 days ]
    To assess the pharmacodynamic dose-response relationship after single subcutaneous injection of HL2351 IL-6 inhibition assay: AUEClast, Emax


Secondary Outcome Measures :
  1. Immunogenicity of HL2351: Anti-drug Antibody [ Time Frame: Day 1, Day 29 ]
    To assess immunogenicity after single subcutaneous injection of HL2351

  2. Tolerability in comparison with Kineret(Anakinra): measured by the occurrence of Adverse Events [ Time Frame: 3 days ]
    To explore tolerability in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  3. Tolerability in comparison with Kineret(Anakinra): measured by Physical Examination, Vital Signs and Safety Laboratory Tests [ Time Frame: 3 days ]
    To explore tolerability in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  4. Tolerability in comparison with Kineret(Anakinra): measured by the occurrence of Local Toxicity [ Time Frame: 3 days ]
    To explore tolerability in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  5. Tolerability in comparison with Kineret(Anakinra): measured by Cytokine Laboratory Test [ Time Frame: 3 days ]
    To explore tolerability in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  6. Pharmacokinetics in comparison with Kineret(Anakinra): Maximum plasma concentration [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  7. Pharmacokinetics in comparison with Kineret(Anakinra): Area under plasma drug concentration-time curve [AUC(0-last), AUCinf] [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  8. Pharmacokinetics in comparison with Kineret(Anakinra): Time of maximum concentration(Tmax) [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  9. Pharmacokinetics in comparison with Kineret(Anakinra): Elimination half-life(T1/2) [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  10. Pharmacokinetics in comparison with Kineret(Anakinra): Apparent Clearance(CL/F) [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  11. Pharmacokinetics in comparison with Kineret(Anakinra): Apparent Volume of Distribution(Vz/F) [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  12. Pharmacokinetics in comparison with Kineret(Anakinra): Mean Residence Time (MRT) [ Time Frame: 3 days ]
    To explore pharmacokinetics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)

  13. Pharmacodynamics in comparison with Kineret(Anakinra): IL-6 inhibition assay [ Time Frame: 1 day ]
    To explore pharmacodynamics in comparison with subcutaneous administration of a positive comparator, Kineret(Anakinra)



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. A healthy adult man aged between 20 and 45 years (inclusive) at screening
  2. Weight between 55 and 90 kg (inclusive) and the body mass index(BMI) between 18.0 and 27.0 (inclusive)

    • BMI(kg/m2) = Body weight (kg)/{height (m)}2
  3. Voluntary consent to participation in this study and signature on the IRB-approved informed consent form after being explained about characteristics of this clinical study, prior to any screening test

Exclusion Criteria:

  1. Current or history of a clinically significant hepatic, renal, neurological, immunological, respiratory or endocrine disease or hematological or oncological disease, cardiovascular disease or psychiatric disease (mood disorder or compulsive disorder, etc.) (in case of a hepatic disease, a hepatitis virus-infected subject may be also included)
  2. Hypersensitivity to a drug (aspirin or antibiotics, etc.) or past history of clinically significant hypersensitivity
  3. In sitting vital signs measured after resting for 3 min or more, systolic blood pressure of <90mmHg or >150mmHg, or diastolic blood pressure of <60mmHg or >100 mmHg
  4. Past history of drug abuse or positive urine drug screening results
  5. Use of any prescription medicine or oriental medicine within 2 weeks or use of any over-the-counter(OTC) medication or vitamin preparation within 1 week prior to the scheduled first dose (however, a subject may be included if other conditions are satisfied, at the discretion of the investigator)
  6. Participation in another clinical study and administration of a drug within 3 months prior to the scheduled first dose (from the dosing day)
  7. Whole blood donation within 2 months or apheresis within 1 month prior to the scheduled first dose, or transfusion within 1 month prior to the first dose
  8. A habitual drinker (>21 units/week, 1 unit = 10 g of pure alcohol) or a person who cannot abstain from alcohol consumption during hospitalization
  9. A smoker of 10 cigarettes/day on average over the past 3 months or a person who cannot abstain from smoking during hospitalization
  10. A person who is planning to get pregnant during the study or who cannot practice acceptable contraception (example: surgical sterilization of a subject or a partner, intrauterine device used by a partner, barrier contraception, diaphragm or condom used in combination) even if not planning to get pregnant
  11. Notable prolongation of the QT/QTcb interval at screening (e.g., repeated confirmation of QTcb interval > 450 ms)
  12. Confirmed history of a risk factor for TdP (e.g., heart failure, hypokalemia, family history of a long QT syndrome)
  13. Chronic, uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosis)
  14. Pyrexia of ≥38°C within 1 week prior to administration of the investigational product
  15. Past history of tuberculosis infection and/or positive Quantiferon TB-Gold test results at screening
  16. A person who had participated in this study and received the investigational product
  17. A person who is otherwise determined as not eligible for clinical study participation by the investigator due to other reasons including clinical laboratory test results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02175056


Locations
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Korea, Republic of
HANDOK Inc.
Seoul, Korea, Republic of
Sponsors and Collaborators
Handok Pharmaceuticals Co., Ltd.
Investigators
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Principal Investigator: Hyeong Ki Lee, Professor Clinical Trial Center, Seoul National University Hospital

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Responsible Party: Handok Pharmaceuticals Co., Ltd.
ClinicalTrials.gov Identifier: NCT02175056     History of Changes
Other Study ID Numbers: HL_C101
First Posted: June 26, 2014    Key Record Dates
Last Update Posted: October 6, 2015
Last Verified: October 2015

Keywords provided by Handok Pharmaceuticals Co., Ltd.:
First In Human
CAPS, SoJIA, AOSD, Bechet Disease, Rheumatoid arthritis

Additional relevant MeSH terms:
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Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents