A Validation and Dosimetry Study of GSK2634673F PET Ligand

Study Overview
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Brief Summary
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This is a methodology study to examine the quantification of GSK2634673F binding in humans, with the aim of characterising a robust, non-invasive method to quantify the specific binding signal for the alpha(V)beta6 protein in human tissues. This will be the first time that this micro-dose ligand is administered to humans. The study will consist of three parts; Part A, Part B and Part C. Healthy subjects will be recruited into Parts A and B of the study in order to gain experience with the GSK2634673F positron emission tomography (PET) ligand and to optimise the scanning procedures prior to administration to IPF patients in Part C.

Official Title
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Validation and Dosimetry Study of [18F]-FBA-A20FMDV2 PET Ligand for Alpha(V)beta6 in Healthy Subjects and in the Lungs of Idiopathic Pulmonary Fibrosis (IPF) Subjects (PETAL Study)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Other: GSK2634673F


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ambulant and capable of attending a PET scan visit as an outpatient. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and an understanding of spoken English. A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal female with a documented tubal ligation or hysterectomy [for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 21.7 - 153.0 International units per liter (IU/L) and oestradiol <110 picomole per liter (pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from after Scan 1 and until the follow-up contact. Male subjects >=45 years and female subjects >=55 years at the time of signing the informed consent. Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test. Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19.0 - 31.0 kg/meter (m)^2 (inclusive). Additional Inclusion Criteria for Part A and B (healthy subjects): Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, vital signs, previous laboratory studies, and other tests. Additional Inclusion Criteria for Part C (IPF subjects): A diagnosis of IPF according to the consensus criteria. 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 or suffers from claustrophobia or subject feels unable to lie flat and still on their back for a period of up to 4 hours in the PET/CT scanner (note that periodic rest intervals will be allowed as required). Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure resulting in radiation exposure greater than 10 mSv over the past 3 years or greater than 10 mSv in a single year including the proposed study. Clinical exposure from which the subject receives a direct benefit is not included in these calculations. 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 test for human immunodeficiency virus (HIV) antibody. Clinically significant anaemia- Hemoglobin <11 grams per deciliter. Clinically significant thrombocytopenia or an abnormal blood coagulation profile. Other Criteria Previous or current exposure to animals that may harbour the foot and mouth disease virus (FMDV2). Previous long term (>= 3 months) residence in a country where FMDV2 is endemic (such as certain areas of Africa, Asia and South America). Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56 day period.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Part A<br>In Part A, up to 6 healthy subjects will be enrolled in order to determine the human radiodosimetry following administration of the PET radioligand. | Other: GSK2634673F<br>* GSK2634673F is a synthetic peptide derived from the foot and mouth disease virus (FMDV2). GSK2634673F will be injected into a cubital or forearm vein intravenously and emission data acquired for up to 240 minutes. This radioactive ligand binds potently and specifically to the integrin alpha(V)beta6.<br>* Other names: PET radiolabelled molecule;|
| Other: Part B<br>In Part B, up to 8 healthy subjects will be recruited to provide sufficient PET data to quantify the uptake and distribution of GSK2634673F in healthy subjects. | Other: GSK2634673F<br>* GSK2634673F is a synthetic peptide derived from the foot and mouth disease virus (FMDV2). GSK2634673F will be injected into a cubital or forearm vein intravenously and emission data acquired for up to 240 minutes. This radioactive ligand binds potently and specifically to the integrin alpha(V)beta6.<br>* Other names: PET radiolabelled molecule;|
| Other: Part C<br>In Part C, up to 20 IPF subjects will be recruited to provide sufficient PET data to quantify the uptake and distribution of GSK2634673F in IPF subjects and, if appropriate, potentially quantify the test/re-test variability. | Other: GSK2634673F<br>* GSK2634673F is a synthetic peptide derived from the foot and mouth disease virus (FMDV2). GSK2634673F will be injected into a cubital or forearm vein intravenously and emission data acquired for up to 240 minutes. This radioactive ligand binds potently and specifically to the integrin alpha(V)beta6.<br>* Other names: PET radiolabelled molecule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Radiation effective dose (Millisievert [mSV]/Megabecquerel [MBq]) for whole body | Radiodosimetry will be determined following administration of the GSK2634673F PET radioligand | 1 day | 
| Part B and C: Uptake and distribution of GSK2634673F in organs of interest (volume of distribution [VT], binding potential [BP] and/or standardised uptake values [SUV]) | The utility of GSK2634673F to quantify integrin alpha(V)beta6 availability in healthy subjects (Part B) and in the lungs of patients with IPF (Part C) will be determined. | Up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Critical time for scanning post-administration of GSK2634673F | Scanning will be started at the same time as injection of the radioligand and data will be collected for up to 240 minutes | 1 day | 
| Part B: Analysis method to quantify integrin alpha(V)beta6 expression from the healthy subject data for use in Part C |  | 1 day | 
| Part C: Qualitative assessment of the relationship between the distribution of fibrosis in the lungs from IPF patients and the uptake of GSK2634673F | High Resolution Computerised Tomography scan (HRCT) of the lungs will be done to allow the potential establishment of areas of fibrosis in the patient lung | Up to 2 weeks | 
| Part C: Comparison of VT, BP and/or SUV in IPF versus healthy lungs |  | Up to 2 weeks | 
| Part C: Test/re-test variability of VT, BP and/or SUV | IPF patients may receive a repeat GSK2634673F PET/Computed tomography (CT) in order to determine the variability in αvβ6 expression over time and allow test/re-test variability to be assessed | Up to 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Pulmonary Fibrosis (IPF), dosimetry, Positron Emission Tomograph (PET)