GKT137831 in IPF Patients With Idiopathic Pulmonary Fibrosis (GKT137831)

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of GKT137831 in Patients With Idiopathic Pulmonary Fibrosis

A placebo-controlled, multicenter, randomized trial to test GKT137831 in ambulatory patients with idiopathic pulmonary fibrosis. This drug is an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) isoforms. The investigators hypothesize the drug will decrease pulmonary injury due to reactive oxygen species (ROS) generated by NOX enzymes, which are believed to play an important role in the development of IPF. Treatment with GKT137831 could result in significant benefit for a lung disease that has, until now, been almost invariably inexorable.

This clinical trial represents the bedside application of a series of NOX translational and basic studies and discoveries, over several years, from the laboratory of Dr. Victor Thannickal.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: GKT137831; Other: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 40-85 years old.
2. A diagnosis of IPF that fulfills current American Thoracic Society (ATS) Consensus Criteria.
3. IPF duration <5 years, based on the date of definitive diagnosis.
4. Ability and willingness to give informed consent and adhere to study requirements.
5. Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) >70% of predicted values

Exclusion Criteria:

1. Diagnosis of major comorbidities expected to interfere with study participation
2. History of malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, the latter defined as stage T1 or T2a, with prostate specific antigen <10 ng/dl. NOX inhibition is not known to promote cancer, and these criteria are within current guidelines.
3. The occurrence of any acute infection requiring systemic antibiotic therapy within 2 weeks prior to Screening (Visit 1).
4. Treatment for >14 days within the preceding month with >20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, etc.), given increased risks of opportunistic infections.
5. Treatment with any investigational agent within 4 weeks of Screening (Visit 1) or 5 half-lives of the investigational medicinal product (whichever is longer).
6. Fertile women who do not agree to contraception or abstinence, or who are breast feeding. IPF is a disease of older adults, and male predominant, so this will not be a frequent consideration.
7. Subjects with known hypersensitivity to GKT137831 or its excipients (e.g. capsule "bulking" agents).
8. A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin < 10.0 g/dL (or 6.2 mmol/L).
9. Severe cardiovascular disease, defined as any of the following within the preceding 12 weeks: acute myocardial infarction or unstable angina, a coronary revascularization procedure, congestive heart failure (NYHA Class III or IV), or stroke, including a transient ischemic attack.
10. Evidence of cardiac conducting abnormalities, defined as second or third degree atrial-ventricular (AV) block not successfully treated with a pacemaker, or a personal or family history of long QT syndrome (QTc interval >450 msec for males or 470 msec for females).
11. End-stage renal disease requiring dialysis.
12. Undergoing transplantation evaluation, or listed with the United Network for Organ Sharing (UNOS) as a lung transplantation candidate at the time of enrollment in this trial.
13. Liver function tests (transaminases, alkaline phosphatase, direct and total bilirubin) >3x upper limit of normal values

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GKT137831; GKT137831 will be administered orally, at a dose of 400 mg twice daily, for a total of 24 weeks.	Drug: GKT137831; GKT137831 is a NOX enzyme inhibitor
Placebo Comparator: Placebo Oral Tablet; Identically-appearing placebo oral tablets will be administered orally, twice daily, for a total of 24 weeks.	Other: Placebo Oral Tablet; see Arm/Group description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surrogate Biomarker of Oxidative Stress by Mass Spectroscopy	Changes in concentrations of circulating o,o'-dityrosine, as determined by mass spectroscopy in plasma, in terms of absolute concentrations and percentages of baseline, will be compared within and between treatment arm participants.	From baseline thru week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collagen Degradation Product by Enzyme Linked Immunoabsorbant Assay	Changes in concentrations of the collagen degradation product, serum C1M measured by enzyme linked immunsorbent assays will be compared between baseline values and those at 24 weeks, and between experimental arm and control participants.	Baseline to week 24
Pulmonary Function by Spirometry	Forced vital capacity (FVC), measured by spirometer at baseline, will be compared to values at the conclusion of the study and between the two treatment arms.	Baseline to week 24
Ambulatory Ability by Measuring Walk Distance in Six Minutes	Six-minute walk distance (6MWD) will be compared at baseline and as changes from baseline among experimental arm participants and control subjects	Baseline to week 24
Evaluation of Safety by Adverse Events	The number of participants who had adverse events will be compared between experimental arm participants and those in the control arm.	Up to week 24

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: University of Michigan; Tulane University; Temple University
• Investigators: Principal Investigator: Steven R Duncan, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): November 30, 2024

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Reactive oxygen species (ROS); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; setanaxib
• Other Study ID Numbers: IRB-300001635

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No