A Phase 1, Randomized, Double-Blind (Sponsor Open), Placebo-Controlled, Single Dose Escalation Trial to Evaluate the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of GSK3050002 (Anti-CCL20 Monoclonal Antibody) in Healthy Male Volunteers
Overview
- Phase
- Phase 1
- Intervention
- GSK3050002
- Conditions
- Colitis, Ulcerative
- Sponsor
- GlaxoSmithKline
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Number of subjects with adverse events
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
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).
Exclusion Criteria
- •Criteria Based Upon Medical Histories
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>21 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- •History of severe drug allergies including type 1 hypersensitivity reaction to parental administration of contrast agents, human or murine proteins or monoclonal antibodies.
- •Subject has acne which requires prescription treatment
- •Criteria Based Upon Diagnostic Assessments
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- •A positive pre-study drug/alcohol screen.
- •A positive test for Human immunodeficiency virus (HIV) antibody.
Arms & Interventions
GSK3050002 0.1 mg
Six subjects in this cohort will receive a single dose of GSK3050002 0.1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects (i.e. 1 subject will be dosed with GSK3050002 and 1 with placebo before the remainder of the cohort is dosed) will be used in the cohort.
Intervention: GSK3050002
GSK3050002 0.1 mg
Six subjects in this cohort will receive a single dose of GSK3050002 0.1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects (i.e. 1 subject will be dosed with GSK3050002 and 1 with placebo before the remainder of the cohort is dosed) will be used in the cohort.
Intervention: Placebo
GSK3050002 0.5 mg
Six subjects in this cohort will receive a single dose of GSK3050002 0.5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: GSK3050002
GSK3050002 0.5 mg
Six subjects in this cohort will receive a single dose of GSK3050002 0.5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: Placebo
GSK3050002 1 mg
Six subjects in this cohort will receive a single dose of GSK3050002 1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort
Intervention: GSK3050002
GSK3050002 1 mg
Six subjects in this cohort will receive a single dose of GSK3050002 1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort
Intervention: Placebo
GSK3050002 5 mg
Six subjects in this cohort will receive a single dose of GSK3050002 5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: GSK3050002
GSK3050002 5 mg
Six subjects in this cohort will receive a single dose of GSK3050002 5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: Placebo
GSK3050002 10 mg
Six subjects in this cohort will receive a single dose of GSK3050002 10 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: GSK3050002
GSK3050002 10 mg
Six subjects in this cohort will receive a single dose of GSK3050002 10 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: Placebo
GSK3050002 20 mg
Six subjects in this cohort will receive a single dose of GSK3050002 20 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: GSK3050002
GSK3050002 20 mg
Six subjects in this cohort will receive a single dose of GSK3050002 20 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of subjects with adverse events
Time Frame: Up to Day 98
Adverse events will be collected from the start of study treatment until the follow-up contact
Vital signs as a measure of safety
Time Frame: Up to Day 98
Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate
Laboratory measurements
Time Frame: Up to Day 98
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests
Electrocardiogram (ECG) assessment as a measure of safety
Time Frame: 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
Pharmacokinetic (PK) parameters after a single intravenous dose of GSK3050002
Time Frame: 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)
Secondary Outcomes
- Chemokine (C-C motif) ligand 20 (CCL20) levels in blood(Up to Day 87)
- Immunogenicity development as assessed from anti-drug antibody(Up to Day 87)