The purpose of the study is to investigate to what extent ShK-186 is tolerated. How quickly and to what extent ShK-186 is absorbed and eliminated from the body (this is called pharmacokinetics) will be investigated.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics: plasma drug concentrations, pharmacokinetic parameters
Safety: adverse events, vital signs, ECG-parameters, laboratory parameters,
physical examination
Secondary outcome
n/a
Background summary
ShK-186 is a new investigational compound that may eventually be used for the
treatment of several autoimmune diseases. In an autoimmune disease the immune
system recognizes the body*s own cells and/or substances as foreign. This may
result in the formation of antibodies against one*s own tissues. ShK-186 can
possibly inhibit this autoimmune response.
ShK-186 is not registered as a drug. This is the first time that this compound
is being given to humans.
Study objective
The purpose of the study is to investigate to what extent ShK-186 is tolerated.
How quickly and to what extent ShK-186 is absorbed and eliminated from the body
(this is called pharmacokinetics) will be investigated.
Study design
This is a single-center, double-blind, placebo-controlled study with 7 planned
successive escalating cohorts, each containing approximately 8 subjects. Each
group of 8 subjects will be split. The first two subjects will be dosed on the
same day (one ShK 186 and one placebo). After dosing, the safety and
tolerability of ShK-186 in these subjects will be closely monitored for 24
hours. If there are no concerns about the safety and tolerability, then the
remaining 6 subjects will be dosed at least two days (48 hours) after the first
two subjects.
Procedures and assessments:
Screening and follow-up: medical history, vital signs (temperature, respiratory
rate, and supine blood pressure and pulse), 12-lead electrocardiogram (ECG),
clinical laboratory (clinical chemistry, haematology, and urinalysis),
pregnancy test (females only) and immunogenicity; at eligibility screening:
informed consent, demographics, weight, height, Body Mass Index (BMI),
hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and
anti-human immunodeficiency virus (HIV)1/2, and drug screen; to be repeated
upon submission: weight, medical history (interim medical history only),
12-lead ECG, vital signs (temperature, respiratory rate, and supine blood
pressure and pulse), clinical laboratory (clinical chemistry, haematology, and
urinalysis), drug screen, and pregnancy test (females only)
Observation period: one period in the clinic from one day prior until 2 days
after drug administration, followed by 3 ambulant visits
Blood sampling:
for pharmacokinetics of ShK-186 concentrations in plasma: pre-dose, 1 and 5
min, 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 72 h post-dose, and otherwise at each
visit
for immunogenicity: on Day 15
Safety assessments: adverse events and concomitant medications: throughout the
study; vital signs: pre-dose, at multiple timepoints post-dose, and otherwise
daily at each visit; clinical laboratory (including clinical chemistry,
haematology, and urinalysis): pre-dose, 2 and 8 h post-dose, and on Day 2, 4,
8and 15; 12-lead ECG: pre-dose, 5 min post-dose, and on Day 2 and 8
Intervention
Group 1: one 5 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Group 2: one 15 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Group 3: one 30 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Group 4: one 60 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Group 5: one 120 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Group 6: one 240 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Group 7: one 480 mcg SC injection of ShK-186 or placebo on Day 1, after an
overnight fast
Study burden and risks
Registration of adverse effects: During the entire investigation all adverse
effects will be documented.
Blood draw, indwelling canula: During this study less than 500 ml of blood will
be drawn. It is anticipated that an indwelling cannula will be inserted for
blood draws on Day 1 and 2. The blood draws on the other days will be drawn by
direct puncture of the vein.
Heart trace (ECG*s): ECG*s will be made regularly.
As ShK-186 will be administered to humans for the first time in this study, the
adverse effects in man are not known. Since ShK-186 is a protein administered
by injection, there is a possibility for an allergic reaction.
ShK-186 has been studied in animals. Based on effects seen in animal studies,
there is a risk of temporary sensation of tingling, burning, pricking, or
numbness of the skin and nausea or vomiting. These effects may occur shortly
after drug administration and demonstrate a prolonged duration. However, these
adverse effects were generally seen at doses higher than what will be
administered during this study.
219 Terry Ave N, Suite 300
Seattle 98109
US
219 Terry Ave N, Suite 300
Seattle 98109
US
Listed location countries
Age
Inclusion criteria
- healthy male and female subjects
- 18-45 yrs, inclusive
- BMI: 18.0-30.0 kg/m2, inclusive and weigh > 50 kg
- the volunteers did not smoke during at least 30 days prior to the screening
Exclusion criteria
Suffering from hepatitis B, hepatitis C, cancer or HIV/AIDS. In case of participation in another drug study within 90 days before the start of this study or being a blood donor within 60 days from the start of the study. In case of donating more than 1.5 liters of blood in the 10 months prior the start of this study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002200-41-NL |
| CCMO | NL41242.056.12 |