A Proof of Mechanism Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01725139
• Date of registration: 08/11/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Proof of Mechanism Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
• Scientific title: A Randomised, Placebo-controlled, Double-blind, Repeat Dose Escalation Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
• Date of first enrolment: March 8, 2013
• Target sample size: 17
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01725139
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of IPF as determined by a responsible and experienced chest physician and
based on established criteria defined by the American Thoracic Society/European
Respiratory Society: American Thoracic Society/European Respiratory Society
International Multidisciplinary Consensus Classification of the Idiopathic
Interstitial Pneumonias.

- FVC greater than (>) 40% predicted and Diffusing capacity of the Lung for Carbon
Monoxide (DLCO) >30% predicted

- Alanine aminotransferase (ALT) less than (<) 2x upper limit of normal (ULN); alkaline
phosphatase and bilirubin less than or equal to (<=) 1.5xULN.

- QTcB <450 milliseconds (msec) and QTc interval <=480 msec; or QTc <480 msec in
subjects with Bundle Branch Block.

- Male over 45 years of age inclusive, or female over 50 years of age inclusive at the
time of signing the informed consent

- A female subject is eligible to participate if she is of non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or
postmenopausal defined as 12 months of spontaneous amenorrhoea. Females on hormone
replacement therapy (HRT) and whose menopausal status is in doubt will be required to
use one of the contraception, 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 enrolment. For most forms of HRT, at least 2 to 4 weeks should 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. This criterion must be followed from the time of the first
dose of study medication until the follow-up contact.

- Body weight >=40 kilogram (kg) (female), >=50 kg (male), and body mass index (BMI)
between 20 and 35 kg/meter squared (m^2) inclusive.

- Subjects must have left ventricular ejection fraction (LVEF) >=50 % as demonstrated by
a recent echocardiogram (at screening or within 3 months prior to screening).

Exclusion Criteria:

- Current IPF exacerbation

- History of acute coronary syndromes, atrial fibrillation, coronary angioplasty, or
stenting within the past 24 weeks.

- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system

- Uncontrolled hypertension or a history of conditions which could increase the risk of
complications from hypertension

- Current upper or lower respiratory tract infection

- Repeated systolic BP >=160 millimeters of mercury (mmHg) and/or diastolic BP >=90 mmHg
unless they are diabetic, in which case subjects with repeated systolic BP >=145 mmHg
and/or diastolic >=85 mmHg

- Poorly controlled diabetes (HbA1c [glycated hemoglobin (hemoglobin A1c)] >7.5%).

- Clinically significant laboratory assessment outside the reference range unless the
Investigator considers that the finding is unlikely to introduce additional risk
factors and will not interfere with the study procedures

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities

- Previous exposure to ionising radiation >5 millisievert (mSv) in the 3 years prior to
enrolment

- History of regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of >21 units for males or >14 units for females. One unit is
equivalent to 8 g of alcohol: a half-pint (approximately 240 milliliters [mL]) of
beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits

- 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

- Currently taking Pirfenidone or have received Pirfenidone within the previous 30 days

- Unable to refrain from the use of prohibited prescription or non-prescription drugs,
unless in the opinion of the Investigator and GSK Medical Monitor the medication will
not interfere with the study procedures or compromise subject safety

- History of sensitivity to any of the study medications, or components there of or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period

- History of sensitivity to heparin or heparin-induced thrombocytopenia



Age minimum: 45 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: GSK2126458

Drug: Placebo

Primary Outcome(s)

Pharmacodynamic (PD) endpoints pAKT/AKT in platelet-rich plasma and BAL cells, [18F]-FDG-PET/CT [Time Frame: Baseline, Day 1, mid-study BAL visit (Day 5-9) and final dosing day (Day 7, 8, 9 or 10) for each cohort]

Area under the curve (AUC) in blood for GSK2126458 [Time Frame: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort]

Concentration of GSK2126458 in bronchoalveolar lavage fluid (BALF) [Time Frame: Baseline BAL visit and mid-study BAL visit (Day 5-9).]

Maximum observed concentration (Cmax) in blood for GSK2126458 [Time Frame: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort]

Pre-dose (trough) concentration at the end of the dosing interval (Ctrough) in blood for GSK2126458 [Time Frame: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort]

Secondary Outcome(s)

Safety and tolerability of GSK2126458 as assessed by change from baseline in vital signs [Time Frame: Day 1, final dosing day (Day 7, 8, 9 or 10) and follow-up (10-14 days post last dose), for each cohort]

Investigate the effect of GSK2126458 on the frequency and or severity of chronic cough using Leicester Cough Questionnaire (LCQ) in IPF subjects [Time Frame: Day 1 and final dosing day (Day 7, 8, 9 or 10) for each cohort]

Safety and tolerability of GSK2126458 as assessed by change from baseline in electrocardiogram (ECG) [Time Frame: Screening, Day 1 and final dosing day (Day 7, 8, 9 or 10) for each study cohort]

Assessment of FEV1 and FVC using daily hand-held spirometry [Time Frame: Recorded daily from screening until final dosing day (Day 7, 8, 9 or 10) for each cohort]

Safety and tolerability of GSK2126458 as assessed by change from baseline in clinical laboratory parameters [Time Frame: Day 1, mid-study BAL visit (Day 5-9), final dosing day (Day 7, 8, 9 or 10) and follow-up (10-14 days post last dose) for each cohort]

Safety and tolerability of GSK2126458 as assessed by change from baseline in pulmonary function [Time Frame: Recorded daily from screening until final dosing day (Day 7, 8, 9 or 10) for each cohort]

Safety and tolerability of GSK2126458 as assessed by number of subjects with adverse events (AE)s [Time Frame: Baseline up to final dosing day (Day 7, 8, 9 or 10) for each cohort]

Assessment of subject's breathlessness using MRC dyspnoea scale [Time Frame: Day 1 and final dosing day (Day 7, 8, 9 or 10) for each study cohort]

Secondary ID(s)

116711

2012-001376-11

Source(s) of Monetary Support

Please refer to primary and secondary sponsors