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

NCT02829307 | Completed Phase 1 Results

• 1 other identifier: 117169
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug-Related Side Effects and Adverse Reactions

Keywords

89Zirconium; Open label; Pharmacokinetics; Radioactive; Clearance; Biodistribution

Outcome Measures

Primary Outcomes (2)

• Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data

  SUV is a mathematically derived ratio of tissue radioactivity concentration and the injected dose of radioactivity per kilogram of the participant's body weight at a given point in time. SUV was analyzed for each region of interest (ROI) such as liver, kidney, muscle, spleen, heart, lung, bladder, thymus, and if feasible blood and bone. A maximum of 4 PET scans were conducted in each participant. Mean SUV derived from PET-CT has been presented.

  Up to Day 7

• Mean Volume of ROI for Each Organ at All Time Points

  Volume of ROI is the volume specified in organs as measured in PET or CT images. Mean volume of ROI for each organ has been presented.

  Up to Day 7

Secondary Outcomes (18)

• 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

  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

  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

  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

  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

  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

Study Arms (1)

89Zr-GSK3128349

EXPERIMENTAL

Subjects will receive a single dose of 89Zr-GSK3128349 as an intravenous (IV) infusion over 20 minutes to deliver a dose of 1 mg

Drug: 89Zr-GSK3128349 1 mg

Interventions

89Zr-GSK3128349 1 mg DRUG

89Zr-GSK3128349 is a mixture of unlabelled and zirconium-labelled GSK3128349, in the form of solution for IV administration, and is associated with about 15 MBq of radioactivity.

89Zr-GSK3128349

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• PRA Health Sciences for clinical study conduct.: collaborator

Study Sites (1)

GSK Investigational Site

Zuidlaren, 9471 GP, Netherlands

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 12, 2016
• Study Start: August 23, 2016
• Primary Completion: January 27, 2017
• Study Completion: January 27, 2017
• Last Updated: September 7, 2018
• Results First Posted: September 7, 2018

Record last verified: 2018-07

Locations

NL (1)