GKT137831 in IPF Patients With Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis Clinical Trial

— GKT137831  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03865927
• Other study ID #: IRB-300001635
• Status: Recruiting
• Phase: Phase 2
• Start date: September 7, 2020
• Est. completion date: January 1, 2025

Study information

• Verified date: April 2024
• Source: University of Alabama at Birmingham
• Contact: Steven R Duncan, MD
• Phone: 205-934-5018
• Email: srduncan[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 1, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Other:
• Placebo Oral Tablet
see Arm/Group description

Drug:
• GKT137831
GKT137831 is a NOX enzyme inhibitor

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Temple University Medical Center	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Temple University, Tulane University, University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Evaluation of safety by adverse events	The number and severity of adverse events will be compared between experimental arm participants and those in the control arm.	Baseline to week 24