A randomized, double-blind placebo- and active-controlled study of the pharmacokinetics, pharmacodynamics and safety of single ascending doses of HM10660A (LAPS-Interferon Alpha-2B) in healthy male subjects

The drug to be given HM10660A is a new, investigational compound that may
eventually be used for the treatment of hepatitis B, C (viral infections of the
liver) and cancer. Human interferon alfa-2b (IFN*2b) is a protein that modifies
the response of the body's immune system to help fight infections and severe
diseases. It is active against viral infections and the spreading of some types
of cancer in the body. Recombinant human interferon alfa-2B is the same enzyme
produced in bacteria that is used in the treatment of chronic Hepatitis B and C
and some types of cancer. A disadvantage of recombinant human interferon
alfa-2b is the need for frequent administration and the duration of the
treatment (48 weeks). HM10660A is a recombinant human interferon alfa-2b linked
to another human protein in development to make it long acting thus allowing
weekly to monthly injections with a higher effect.
This new compound is not registered as a drug. This is the first time that this
compound is being given to humans.
During the study you may be receiving HM10660A, Pegasys or placebo. Pegasys is
a long-acting interferon that is registered for the use in the treatment of
chronic hepatitis B or C.

to study the safety and tolerability of HM10660A (LAPS-interferon alpha-2b),
including immunogenicity, as compared to Pegasys® (PEG-interferon alpha-2a)
to study the pharmacokinetics and pharmacodynamics of HM10660A (LAPS interferon
alpha-2b) as compared to Pegasys® (PEG-interferon alpha-2a)

Design:
a randomized, double-blind, placebo- and active-controlled, single-dose study
in 4 groups of 12 healthy male subjects each. In each group, 8 subjects will
receive a single subcutaneous (sc) dose of HM10660A, 2 subjects will receive a
single sc dose of placebo and 2 subjects will receive a single sc dose of
Pegasys®.

Screening :
demographics, medical history, clinical laboratory, physical examination
(including height and body weight), vital signs , 12-lead electrocardiogram
(ECG), drug and alcohol screen, HBsAg, anti HCV and anti-HIV 1/2, blood
sampling for anti-glutamic acid decarboxylase ((anti GAD) antibodies and for
anti-thyroid peroxidase (anti-TPO) antibodies, Columbia Suicide Severity Rating
Scale (C-SSRS), adverse events (AEs), previous and concomitant medication, and
eligibility check
Admission :
clinical laboratory (including clinical chemistry, hematology and urinalysis),
physical examination, vital signs (including supine systolic and diastolic
blood pressure, pulse rate and oral body temperature), 12-lead ECG, drug and
alcohol screen, AEs, previous and concomitant medication, and eligibility check
Follow-up (Day 43) :
clinical laboratory (including clinical chemistry, hematology and urinalysis),
physical examination, vital signs (including supine systolic and diastolic
blood pressure, pulse rate and oral body temperature), 12-lead ECG, C-SSRS,
blood sampling for PK and immunogenicity, AEs and concomitant medication
Observation period :
- Groups 1 and 2: in clinic from the afternoon preceding drug administration up
to 168 h (Day 8) after drug administration and ambulatory visits on Days 11,
15, 22 and 29
- Groups 3 and 4: in clinic from the afternoon preceding drug administration up
to 240 h (Day 11) after drug administration and ambulatory visits on Days 15,
22 and 29
Blood sampling :
- for pharmacokinetics (PK) of HM10660A and Pegasys® in serum: at pre-dose and
at 2, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 h and 1008 h post-dose
- for pharmacodynamics (PD; 2*-5*-OAS and neopterin in serum): at pre-dose and
at 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504 and 672 h post-dose
- for immunogenicity: at pre-dose and at 336, 504, 672 and 1008 h post-dose.

Safety assessments :
AEs: throughout the study period
clinical laboratory:
- clinical chemistry and hematology: at 12, 24, 48 and 72 h post-dose and once
on Days 8, 15 and 29;
- urinalysis: at 6 h post-dose;

vital signs (including supine systolic and diastolic blood pressure, pulse rate
and oral body temperature): at 1, 6, 12, 24, 48, 72 and 96 h post-dose and once
on Days 8, 11, 15, 22 and 29;
body temperature only: once on Days 6 and 7

12-lead ECG: at 1, 6, 12, 24, 48, 72 and 96 h post-dose and once on Days 8 and
15;
physical examination (directed by symptoms): at 24, 48 and 96 h post-dose and
once on Days 8 and 15;

local tolerability at injection site: at 3, 12, 24, 48 and 72 h post-dose;

C-SSRS: once on Days 8, 11, 15, 22 and 29

Bioanalysis :
- analysis of serum PK samples for HM10660A and Pegasys® by PRA using a
validated method
- analysis of 2*-5*-OAS and neopterin in serum by PRA using a validated method
- analysis of immunogenicity in serum by PRA using a validated method

Active substance: HM10660A, Pegasys (PEG interferon alfa) or placebo

Procedures: pain, light bleeding, heamatoma, possibly an infection.