Clinical trial NCT02829307: A Positron Emission Tomography (PET) Imaging Study to Investigate the Biodistribution and Clearance of an Albumin Binding Domain Antibody (AlbudAb) GSK3128349 in Healthy Male Subjects
Official title: An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium Labeled GSK3128349 to Investigate the Biodistribution and Clearance of an Albumin Binding Domain Antibody (AlbudAb) GSK3128349 Following Single Dose Intravenous Administration in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug-Related Side Effects and Adverse Reactions
Keywords: 89Zirconium
Open label
Pharmacokinetics
Radioactive
Clearance
Biodistribution
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences for clinical study conduct.
First posted: 2016-07-12
Enrollment: 8
Sex: MALE
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: GSK3128349 is a small protein molecule (biopharmaceutical) that binds to albumin in the body, and by itself, has no pharmacological action. A pharmacologically active drug can be attached to GSK3128349 with the goal of changing the distribution and/or duration of action of the attached drug. This study will determine the distribution and pharmacokinetics (duration) of GSK3128349 itself after a single intravenous infusion. GSK3128349 has been labeled with and the radioisotope 89Zirconium allowing it to be visualized in the organs of the body using a PET scanner at multiple time points after GSK3128349 dosing. The data from this study will help predict the distribution of future drugs attached to GSK3128349. The total duration of a subject's participation is about approximately 10 weeks, including the screening period.


Eligibility criteria: Inclusion Criteria:

* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<=1.5x Upper Limit Normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
* Body Mass Index (BMI) within the range 19.0 - 31.0 kilogram (kg)/meter (m\^2) (inclusive).
* Subjects must agree to use one of the contraception methods listed in the protocol.
* Capable of giving written informed consent, which includes compliance with the study requirements and restrictions.
* Average Corrected QT interval (QTc) \<=450 milliseconds (msec)

Exclusion Criteria:

* Current evidence or history of an influenza-like illness.
* 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, or current, acute renal failure, known renal disease, or a renal disorder or abnormality that may compromise renal function. This includes having one kidney.
* Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure that, together with the proposed study, will result in a total radiation exposure greater than 10 mSv over a 3 year period. Clinical exposure from which the subject receives a direct benefit (example, diagnostic test) is not included in these calculations.
* 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 g of alcohol: a half-pint (\~240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

* Unable to refrain from the use of prescription drugs within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* Subject is a smoker \>=5 cigarettes/day or with a smoking history of \>5 pack years
* History of sensitivity to any of the study treatment 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.
* Subject suffers from claustrophobia that limits the ability to remain still in the PET/CT scanner for the required amount of time.
* Subject has metal present in their body that will interfere with the PET/CT scanning.
* Estimate glomerular filtration rate (eGFR) \<60 mL/min/1.73 m\^2 (utilizing the Chronic Kidney Disease Epidemiology Collaboration (CKI-EPI) equation).
* Urine mg protein/mg creatinine Urine Protein Creatinine Ratio (UPCR) \>0.3.
* Evidence of hematuria by urinalysis (1plus or greater dipstick test).
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C (Hep C) antibody result within 3 months of screening.
* A positive test for Human Immunodeficiency Virus (HIV) antibody.
* A positive pre-study drug/alcohol screen.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

Primary outcomes:
measure: Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data
timeFrame: Up to Day 7
measure: Mean Volume of ROI for Each Organ at All Time Points
timeFrame: Up to Day 7
Secondary outcomes:
measure: Area Under Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) and Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [0-inf]) of 89Zr-GSK3128349 and GSK3128349
timeFrame: Pre-dose, 1 hour (h), 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Percent Area Under the Curve Obtained by Extrapolation (AUCex) and Percent Area Under the First Moment Curve Obtained by Extrapolation (AUMCex) of 89Zr-GSK3128349 and GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Maximum Observed Plasma Concentration (Cmax) of 89Zr-GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Cmax of GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Elimination Rate Constant (Lambda-z) of 89Zr-GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Area Under the First Moment Curve From Pre-dose Extrapolated to Infinite Time (AUMC [0-inf]) and Area Under the First Moment Curve From Pre-dose Extrapolated to Last Time of Quantifiable Concentration (AUMC [0-t]) of 89Zr-GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: AUMC (0-inf) and AUMC (0-t) of GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Clearance of 89Zr-GSK3128349 and GSK3128349
timeFrame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
measure: Mean Organ and Effective Dose
timeFrame: Up to Day 7
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 45 days
measure: Number of Participants With Clinical Chemistry Data of Potential Clinical Concern
timeFrame: Up to 45 days
measure: Number of Participants With Hematology Data of Potential Clinical Concern
timeFrame: Up to 45 days
measure: Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern
timeFrame: Pre-dose on Day 1, 1 h and 24 h post-dose on Day 1 and Day 45
measure: Number of Participants With Vital Signs of Potential Clinical Concern
timeFrame: Up to 45 days
measure: Number of Participants With Positive Anti-GSK3128349 Antibody Assay
timeFrame: Pre-dose on Day 1 and Day 43
measure: Serum Titers of Anti-GSK3128349 Antibodies
timeFrame: Pre-dose on Day 1 and Day 43
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: