Last updated: 07/17/2024 16:56:18
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
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Basic Science
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Mean Standardized Uptake Values (SUVs) derived from Positron Emission Tomography-Computer Tomography (PET-CT) data
Timeframe: Up to Day 7
Mean volume of ROI for each organ at all time points
Timeframe: Up to Day 7
Secondary outcomes:
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
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
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
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
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
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
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
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
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
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
Mean organ and effective dose
Timeframe: Up to Day 7
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timeframe: Up to 45 days
Number of participants with clinical chemistry data of potential clinical concern
Timeframe: Up to 45 days
Number of participants with hematology data of potential clinical concern
Timeframe: Up to 45 days
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
Number of participants with vital signs of potential clinical concern
Timeframe: Up to 45 days
Number of participants with positive anti-GSK3128349 antibody assay
Timeframe: Pre-dose on Day 1 and Day 43
Serum titers of anti-GSK3128349 antibodies
Timeframe: Pre-dose on Day 1 and Day 43
Interventions:
Drug: 89Zr-GSK3128349 1 mg
Enrollment:
8
Observational study model:
Not applicable
Primary completion date:
2017-27-01
Time perspective:
Not applicable
Clinical publications:
Kevin S. Thorneloe; Armin Sepp; Sean Zhang; Laura Galinanes-Garcia; Paul Galette; Wasfi Al-Azzam; Danielle J. Vugts; Guus van Dongen; Phillip Elsinga; Johan Wiegers; Andor W.J.M. Glaudemans; Veena Vincent; Jessica Renaux; Matt Szapacs; Mary Birchler; Matthew Cleveland; Mats Bergstrom; Marie Davies. The biodistribution and clearance of AlbudAb, a novel biopharmaceutical medicine platform, assessed via PET imaging in humans. EJNMMI Res. 2019;9:45
DOI: https://doi.org/10.1186/s13550-019-0514-9
PMID: 31115711
Medical condition
Drug-Related Side Effects and Adverse Reactions
Product
GSK3128349, GW589309
Collaborators
PRA Health Sciences for clinical study conduct.
Study date(s)
August 2016 to January 2017
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
50 - 65 years
Accepts healthy volunteers
Yes
- 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).
- 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).
Inclusion and exclusion 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.
Trial location(s)
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2017-27-01
Actual study completion date
2017-27-01
Plain language summaries
Summary of results in plain language
Available language(s): Dutch, English
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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