Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: GSK3008348; Placebo; [18F]-FBA-A20FMDV2
Intervention description: Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal.; Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.; Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Tolerability; IPF; PET imaging; Idiopathic Pulmonary Fibrosis; Safety; Pharmacokinetics; Double-blind

Summary:

      GSK3008348 is being developed as a treatment for IPF. A first-time-in-human study showed that
      single nebulized doses of 1-3000 micrograms (mcg) GSK3008348 in healthy volunteers were well
      tolerated, with pharmacokinetic (PK) exposures within the defined limits set in the protocol.
      The proposed study is a 2-cohort study of single doses, intended to evaluate the safety,
      tolerability and PK of the drug in participants with IPF not currently treated with
      pirfenidone or nintedanib, and to obtain preliminary information on target engagement. Cohort
      1 will be a 2-period, randomized, double-blind, placebo-controlled group with at least 7 days
      washout between doses, and follow-up period of up to 7-14 days. Cohort 2 is optional. It will
      be designed to further explore safety and to provide additional information on the target
      engagement profile of GSK3008348. The total duration of the study will be up to 62 days.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male participants aged >= 50 years, and female participants aged >=55 years, at the
             time of signing the informed consent.

          -  Diagnosis of definite or probable IPF as determined by a responsible and experienced
             chest physician and based on established criteria defined by the American Thoracic
             Society/European Respiratory Society Internationale Multidisciplinary Consensus
             Classification of the Idiopathic Interstitial Pneumonias.

          -  Ambulant and capable of attending outpatient visits.

          -  FVC > 50 percent predicted and DLCO > 40 percent predicted.

          -  Body weight >= 45 kilograms (kg) and body mass index (BMI) within the range 18.0-35.0
             kg/square meter (inclusive).

          -  Male and female

          -  Male participants: A male participant must agree to use contraception as detailed in
             this protocol during the study and for at least 90 days after the follow up visit, and
             refrain from donating sperm during this period.

          -  Female participants: A female participant is eligible to participate if she is not
             pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) as
             defined in the protocol.

          -  Capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions, listed in the informed consent form (ICF) and in this
             protocol.

        Exclusion Criteria:

          -  ALT and bilirubin > 1.5x upper limit of normal (ULN; isolated bilirubin > 1.5xULN is
             acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QT corrected (QTc) > 450 milliseconds (msec), or QTc > 480 msec in participants with
             Bundle Branch Block.

          -  Current IPF exacerbation, or upper or lower respiratory tract infection on admission
             to the clinical unit.

          -  History of or suffers from claustrophobia, or unable to lie flat and still on their
             back for up to 2 hrs in the PET scanner.

          -  Extent of emphysema greater than the extent of fibrotic change on High-Resolution
             Computed Tomography (HRCT) scan, based on investigator judgment.

          -  FEV1/FVC ratio < 0.70 at screening (post-bronchodilator).

          -  History of sensitivity to the study treatment, or components thereof, or a history of
             drug or other allergy that, in the opinion of the investigators or Medical Monitor,
             contraindicates their participation.

          -  Any current oro-pharygneal disease or disorders as judged by the investigator.

          -  Currently taking pirfenidone or nintedanib, or received pirfenidone or nintedanib
             within 30 days of the first dose of study treatment.

          -  Taken, within 7 days or 5 half-lives (whichever is longer) before the first dose of
             study treatment, organic anion transporter (OAT) substrates with a narrow therapeutic
             index (example: methotrexate and tenofovir), vitamins, or dietary or herbal
             supplements, unless in the opinion of the investigator and sponsor the supplement will
             not interfere with the study medication.

          -  Long-term continuous home oxygen therapy (use of oxygen that is only intermittent and
             for symptom relief is acceptable).

          -  Participation in a clinical trial and receipt of an investigational medicinal product
             within the following time period before the first dose 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 4 new investigational medicinal products within 12 months before
             the first dose.

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening, or positive Hepatitis C
             antibody test result at screening or within 3 months before the first dose of study
             treatment.

        Note: participants with a positive Hepatitis C antibody test because of previous, resolved
        disease can be enrolled if a confirmatory negative Hepatitis C Ribonucleic Acid (RNA) test
        is obtained.

          -  Previous or current exposure to animals that may harbour Food 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 loss of blood or blood products in
             excess of 500 milliliter (mL) within 56 days.

          -  History of drug or alcohol abuse that in the opinion of the investigator affects their
             participation in the study.

          -  Exposure to ionizing radiation in excess of 10 Millisievert (mSv) above background
             over the previous 3 year period as a result of occupational exposure or previous
             participation in research studies. Clinically justified (therapeutic or diagnostic)
             exposures are not included in the exposure calculation.