Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging

NCT ID: NCT03069989

Last Updated: 2019-08-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-13
• Study Completion Date: 2018-07-18

Brief 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.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1 GSK3008348

Participants will receive a single nebulized dose of GSK3008348 during each of 2 planned dosing periods and up to 3 microdose administrations of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.

Group Type: EXPERIMENTAL

GSK3008348

Intervention Type: DRUG

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.

[18F]-FBA-A20FMDV2

Intervention Type: DRUG

Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Cohort 1 Placebo

Participants will receive a single nebulized dose of placebo during each of 2 planned dosing periods and up to 3 microdose of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

[18F]-FBA-A20FMDV2

Intervention Type: DRUG

Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Cohort 2 GSK3008348

Participants will receive a single nebulized dose of GSK3008348 during each of 2 planned dosing periods and up to 3 microdose administrations of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.

Group Type: EXPERIMENTAL

GSK3008348

Intervention Type: DRUG

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.

[18F]-FBA-A20FMDV2

Intervention Type: DRUG

Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Cohort 2 Placebo

Participants will receive a single nebulized dose of placebo during each of 2 planned dosing periods and up to 3 microdose of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

[18F]-FBA-A20FMDV2

Intervention Type: DRUG

Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Interventions

GSK3008348

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.

Intervention Type: DRUG

Placebo

Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

Intervention Type: DRUG

[18F]-FBA-A20FMDV2

Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003674-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204715

Identifier Type: -

Identifier Source: org_study_id