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TerminatedPhase 1ACTRN12618001502224

The research project is investigating a new potential treatment for auto-immune diseases (where your own immune system attacks healthy organs and cells by mistake). The study drug being investigated is called HL161BKN.

A Phase 1, randomized, placebo-controlled, ascending dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of HL161BKN following single intravenous and subcutaneous doses in healthy subjects.

Sponsor

IQVIA

Enrollment

64 participants

Start Date

Dec 19, 2017

Study Type

Interventional

Conditions

Auto-Immune Diseases

Summary

HL161BKN is an experimental treatment. This means that it is not an approved treatment for auto-immune diseases in Australia by the Therapeutic Goods Administration (TGA). Auto-immune diseases occur when a person’s own immune system mistakenly attacks their own body, and are particularly hard to treat because there is no cure currently available, only medications that can manage the symptoms. There are over 80 different types of auto-immune diseases that range in severity (from mild to disabling), depending on which system (nervous, vascular, respiratory, muscular etc.) is under attack and to what degree. T lymphocytes (T cells) are immune cells that use special receptors on their surfaces to identify micro-organisms such as bacteria and viruses that may enter our bodies. Usually, the T cells are destroyed by the thymus, an organ of the immune system. Occasionally, they are not destroyed, and these rogue T cells may instruct another type of cell, B lymphocytes (B cells), to make antibodies against the body’s own tissues, organs or systems. Such antibodies are called 'autoantibodies'. HL161BKN acts as a “block” of special receptors in the tissues, organs or systems, so that autoantibodies cannot bind to them and cause an auto-immune reaction that causes damage.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 55 Yearss

Inclusion Criteria13

  • Subject has a body mass index (BMI) range of 18.5 to 32.0 kg/m2, inclusive, and weighs at least 50 kg and <100 kg at screening.
  • Healthy as determined by pre-study medical history, physical examination, vital signs and 12-lead ECG.
  • Review of immunization history to hepatitis B and diphtheria and tetanus (DT). Although desired, official immunization records are not required.
  • Normal clinical laboratory test results, or where outside the reference range judged as not clinically relevant by the Investigator.
  • Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-child-bearing potential, confirmed at screening by fulfilling one of the following criteria:
  • Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
  • Documented permanent surgically sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy).
  • Male subjects and their female spouse/partners who are of childbearing potential must be using 2 forms of birth control (one of which is an highly effective method and 1 must be a barrier method, or agree to abstinence, starting at screening and continue throughout the study period and for 60 days after the final study drug administration.
  • Male subject must not donate sperm starting at screening and throughout the study period and for 60 days after the final study drug administration.
  • Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the Informed Consent Form (ICF) until completion of the last study visit.
  • Subjects who are non-smokers who have not used tobacco products or nicotine-containing products (including nicotine patches) for at least 3 months preceding screening.
  • Subject has adequate venous access.
  • Willing and able to comply with scheduled visits, treatment plan, clinical laboratory tests and other trial procedures including standardized meals.

Exclusion Criteria28

  • Female subjects of child bearing potential.
  • Subject has a known or suspected hypersensitivity to HL161BKN, or any components of the formulation used.
  • Subject has had previous exposure toHL161BKN.
  • Subject with liver chemistry tests (AST, ALT, ALP, and total bilirubin) equal to 1.25 × ULN at screening or above the ULN at Day -1.
  • A subject with marginally elevated fasting unconjugated serum bilirubin with documented Gilbert's syndrome may be enrolled.
  • Subject with an Estimated GFR of < 75mL/min for women and < 85mL/min for men (based on Cockcroft-Gault equation).
  • Subject has a total IgG level of <900 mg/dL at screening.
  • Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies or exercise-induced asthma prior to study drug administration).
  • Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinology, hematology, hepatic, immunology, metabolism, urology, pulmonary, neurology, dermatology, psychiatry, renal, or other major disease or malignancy, as judged by the Investigator.
  • Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to admission (Day -1).
  • Subject has had their spleen removed.
  • Subject has a past medical history of primary immunodeficiency, T-cell or humeral, including common variable immunodeficiency.
  • Subject has an active infection (eg, sepsis, pneumonia, and abscess) or has had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks before the first dose of IMP.
  • Subject has any major episode of infection requiring hospitalization or treatment with IV anti-infective agents within 6 weeks prior to screening or oral anti-infective agents within 2 weeks prior to screening.
  • Subject has any clinically significant abnormality following the Investigator’s review of the physical examination, ECG and protocol defined clinical laboratory tests at screening or Day -1.
  • Subject has a mean pulse <40 or >100 bpm; mean systolic blood pressure >140 mmHg; mean diastolic blood pressure >90 mmHg at Day -1.
  • Subject has a mean QTcF interval of >430 ms (for males) and >450 ms (for females) at Day -1.
  • Subject has used any prescribed or nonprescribed drugs (including vitamins, hormone replacement therapy, natural, and herbal remedies, eg, St. John’s Wort) in 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g per day).
  • Subject has a history of drinking more than 21 units of alcohol per week (1 unit is equal too 10 g pure alcohol, equal too 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) (greater than 14 units of alcohol for female subjects) during the 3 months prior to admission to the study center or the subject tests positive for alcohol or drugs of abuse at screening or Day -1.
  • Subject has used any drugs of abuse within 3 months prior to admission to the study center.
  • Subject has used any inducer of metabolism (eg, barbiturates, rifampin) 1 month prior to admission to the study center or any strong inhibitor of drug or xenobiotic metabolism (such as CYP3A4 inhibitor itraconazole) within 2 weeks prior to admission to the study.
  • Subject has had significant blood loss, donated 1 unit (450 mL) or more of blood, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to Day -1.
  • Subject has a positive serology test for HBsAg, hepatitis B core antibody (anti-HBc), hepatitis C virus antibodies (anti-HCV), or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
  • Subject has a positive T-cell interferon-y release assay (TIGRA), ie, Quanti-FERON-TB Gold test, at screening. Subjects with an indeterminate result should have negative purified protein derivative (PPD) skin test and low risk of acquiring tuberculosis (TB) (eg, no close contact with TB-positive individual[s]), and/or chest x-ray performed within 6 months before the screening visit showing no evidence of latent/active TB.
  • Note: Subjects who have a negative Quanti-FERON-TB Gold test results from 28 days prior to screening, with no history of exposure to a person with TB or travel to endemic region in the same period, may be enrolled without the need to repeat QuantiFERON test post-signing of ICF.
  • Subject has participated in any clinical study or has been treated with any investigational drugs within 28 days or 5 half-lives whichever is longer, prior to screening.
  • Subject will require an immunization within 6 weeks following the last dose administered in this study.
  • Subject has any condition which, in the Investigator’s opinion, makes the subject unsuitable for study participation.

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Interventions

Each participant will only receive One treatment Arm for the trial. Arms 8 and 9 will be decided by the Safety Monitoring Committee after review of all other cohorts, safety and PK/PD data. Arm 1:

Each participant will only receive One treatment Arm for the trial. Arms 8 and 9 will be decided by the Safety Monitoring Committee after review of all other cohorts, safety and PK/PD data. Arm 1: HL161BKN or Placebo 0.1mg/kg Once Intravenous Infusion administered over 60 minutes Arm 2 HL161BKN or Placebo 0.5mg/kg Once Subcutaneous Injection Arm 3 HL161BKN or Placebo 1.5mg/kg Once Subcutaneous Injection Arm 4 HL161BKN or Placebo 3mg/kg Once Subcutaneous Injection Arm 5 HL161BKN or Placebo 3mg/kg Once Intravenous Infusion administered over 60 minutes Arm 6 HL161BKN or Placebo 7mg/kg Once Subcutaneous Injection Arm 7 HL161BKN or Placebo 10mg/kg Once Subcutaneous Injection Arm 8 HL161BKN or Placebo Dose to be decided Once Subcutaneous Injection Arm 9 HL161BKN or Placebo Dose to be decided Once Subcutaneous Injection At the conclusion of each dose group a safety monitoring committee will review all PK/PD and safety data to ensure increasing to the next dose level is safe to do so.

Locations(1)

Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston

QLD, Australia

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ACTRN12618001502224