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

NCT02175056 | Completed Phase 1

• 1 other identifier: HL_C101
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

First In Human; CAPS, SoJIA, AOSD, Bechet Disease, Rheumatoid arthritis

Outcome Measures

Primary Outcomes (12)

• Tolerability as measured by the occurrence of Adverse Events

  Adverse Events after single subcutaneous dose of HL2351 : check Day -1, 1, 2, 3, 4, 5, 7, 11, 15, 22, 29

  29 days

• Tolerability as measured by Physical Examination, Vital Signs and Safety Laboratory Tests

  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

  29 days

• Tolerability as measured by the occurrence of Local Toxicity

  Local Toxicity after single subcutaneous dose of HL2351 : check Day 1, 2, 4

  4 days

• Tolerability as measured by Cytokine Laboratory Test

  Cytokine Laboratory Test after single subcutaneous dose of HL2351 : check Day 1, 2, 4

  4 days

• Pharmacokinetics of HL2351: Maximum plasma concentration(Cmax)

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacokinetics of HL2351: Area under plasma drug concentration-time curve [AUC(0-last), AUCinf]

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacokinetics of HL2351: Time of maximum concentration(Tmax)

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacokinetics of HL2351: Elimination half-life(T1/2)

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacokinetics of HL2351: Apparent Clearance(CL/F)

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacokinetics of HL2351: Apparent Volume of Distribution(Vz/F)

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacokinetics of HL2351: Mean Residence Time (MRT)

  To assess pharmacokinetics after single subcutaneous injection of HL2351

  29 days

• Pharmacodynamics of HL2351: IL-6 inhibition assay

  To assess the pharmacodynamic dose-response relationship after single subcutaneous injection of HL2351 IL-6 inhibition assay: AUEClast, Emax

  7 days

Secondary Outcomes (13)

• Immunogenicity of HL2351: Anti-drug Antibody

  Day 1, Day 29

• Tolerability in comparison with Kineret(Anakinra): measured by the occurrence of Adverse Events

  3 days

• Tolerability in comparison with Kineret(Anakinra): measured by Physical Examination, Vital Signs and Safety Laboratory Tests

  3 days

• Tolerability in comparison with Kineret(Anakinra): measured by the occurrence of Local Toxicity

  3 days

• Tolerability in comparison with Kineret(Anakinra): measured by Cytokine Laboratory Test

  3 days

Study Arms (3)

HL2351

EXPERIMENTAL

1, 2, 4, 8, 12 mg/kg (SC) / Single-Dose

Biological: HL2351

Placebo

PLACEBO COMPARATOR

1, 2, 4, 8, 12 mg/kg (SC) / Single-Dose

Biological: HL2351

Kineret(Anakinra)

ACTIVE COMPARATOR

100 mg (SC) / Single-Dose

Biological: Kineret(Anakinra)

Interventions

HL2351 BIOLOGICAL

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.

HL2351; Placebo

Kineret(Anakinra) BIOLOGICAL

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.

Kineret(Anakinra)

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A healthy adult man aged between 20 and 45 years (inclusive) at screening
• 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
• 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

You may not qualify if:

• 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)
• Hypersensitivity to a drug (aspirin or antibiotics, etc.) or past history of clinically significant hypersensitivity
• 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
• Past history of drug abuse or positive urine drug screening results
• 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)
• Participation in another clinical study and administration of a drug within 3 months prior to the scheduled first dose (from the dosing day)
• 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
• A habitual drinker (\>21 units/week, 1 unit = 10 g of pure alcohol) or a person who cannot abstain from alcohol consumption during hospitalization
• A smoker of 10 cigarettes/day on average over the past 3 months or a person who cannot abstain from smoking during hospitalization
• 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
• Notable prolongation of the QT/QTcb interval at screening (e.g., repeated confirmation of QTcb interval \> 450 ms)
• Confirmed history of a risk factor for TdP (e.g., heart failure, hypokalemia, family history of a long QT syndrome)
• Chronic, uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosis)
• Pyrexia of ≥38°C within 1 week prior to administration of the investigational product
• Past history of tuberculosis infection and/or positive Quantiferon TB-Gold test results at screening

Sponsors & Collaborators

• Handok Inc.: lead

Study Sites (1)

HANDOK Inc.

Seoul, South Korea

Location

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes; Arthritis, Rheumatoid

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Inducible Urticaria; Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Cold Urticaria; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Hyeong Ki Lee, Professor

  Clinical Trial Center, Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 26, 2014
• Study Start: May 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 6, 2015

Record last verified: 2015-10

Locations

KR (1)