Colitis, Ulcerative
Conditions
Keywords
safety, GSK3050002, CCR6 receptor, single dose escalation, Phase 1, CCL20
Brief summary
The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Subjects will be admitted to the clinical unit the evening prior to dosing when each subject will receive a single intravenous dose of GSK3050002 or placebo, then remain in house under supervision until discharged on Day 3. Subjects will then return for 7 outpatient visits scheduled over the following 81 days. Finally, the follow-up visit will be 7-14 days following the last visit.
Interventions
DRUGGSK3050002
GSK3050002 is a white to off-white lyophilized powder that will be reconstituted with sterile water for intravenous infusion. It is available in the concentrations of 0.1 milligram (mg)/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg.
DRUGPlacebo
Placebo contains normal saline (0.9% sodium chloride) for intravenous infusion
Sponsors
Eisai Inc.
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12- lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
may be included only if the Investigator in consultation with the GSK Medical Monitor \[if required\] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body mass index (BMI) within the range 18 - 29 kilogram per meter square \[kg/m\^2\] (inclusive). * Male subjects with female partners of child-bearing potential must agree to use one of the listed contraception methods. This criterion must be followed for 1 month prior to the first dose of study medication for 15 weeks post dose. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Suitable for cannulation and with adequate venous access. * Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<= 1.5xUpper limit of Normal \[ULN\] (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Based on a single ECG QTcF \< 450 milliseconds (msec).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory measurements | Up to Day 98 | Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests |
| Vital signs as a measure of safety | Up to Day 98 | Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate |
| Pharmacokinetic (PK) parameters after a single intravenous dose of GSK3050002 | Day 1, Day 2, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84 | The following PK parameters will be determined: maximum observed serum concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC\[0-t\] and AUC\[0-infinity\]), and apparent terminal phase half-life (t1/2) |
| Number of subjects with adverse events | Up to Day 98 | Adverse events will be collected from the start of study treatment until the follow-up contact |
| Electrocardiogram (ECG) assessment as a measure of safety | Up to Day 98 | Triplicate 12-lead ECG will be recorded before dosing on Day 1 (Pre-dose) and a single 12-lead ECG will be obtained at all other timepoints |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity development as assessed from anti-drug antibody | Up to Day 87 | An assay for detecting anti-drug antibodies (ADA) against GSK305002 will be developed and validated using an electrochemiluminescent (ECL) bridging assay. Testing will be performed using the typical tiered approach involving screening, confirmation, and titration assays. If sera contain potential anti- GSK3050002 antibodies, they will be confirmed by immunocompetition using excess drug. Confirmed samples with such antibodies will be further analyzed for titers and may be characterized for neutralizing activity by a neutralization assay |
| Chemokine (C-C motif) ligand 20 (CCL20) levels in blood | Up to Day 87 | Whole blood may be collected for in vitro stimulation and measurement of CCL20 activity in a biological assay. Analysis of serum levels of total (free and drug bound) CCL20 may be performed |
Countries
United Kingdom
Outcome results
None listed