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

NCT ID: NCT02829307

Last Updated: 2018-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-23
• Study Completion Date: 2017-01-27

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

89Zr-GSK3128349

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

Group Type: EXPERIMENTAL

89Zr-GSK3128349 1 mg

Intervention Type: 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.

Interventions

89Zr-GSK3128349 1 mg

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

PRA Health Sciences for clinical study conduct.

UNKNOWN

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Zuidlaren, , Netherlands

Countries

Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

117169

Identifier Type: -

Identifier Source: org_study_id