GKT137831 in IPF Patients with Idiopathic Pulmonary Fibrosis

NCT03865927 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: IRB-300001635
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Reactive oxygen species (ROS); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Collagen degradation product by enzyme linked immunoabsorbant assay

  Baseline to week 24

• Pulmonary function by spirometry

  Baseline to week 24

• Ambulatory ability by measuring walk distance in six minutes

  Baseline to week 24

• Evaluation of safety by adverse events

  Baseline to week 24

Study Arms (2)

GKT137831

EXPERIMENTAL

GKT137831 will be administered orally, at a dose of 400 mg twice daily, for a total of 24 weeks.

Drug: GKT137831

Placebo Oral Tablet

PLACEBO COMPARATOR

Identically-appearing placebo oral tablets will be administered orally, twice daily, for a total of 24 weeks.

Other: Placebo Oral Tablet

Interventions

Placebo Oral Tablet OTHER

see Arm/Group description

Placebo Oral Tablet

GKT137831 DRUG

GKT137831 is a NOX enzyme inhibitor

GKT137831

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Diagnosis of major comorbidities expected to interfere with study participation
• 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.
• The occurrence of any acute infection requiring systemic antibiotic therapy within 2 weeks prior to Screening (Visit 1).
• 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.
• Treatment with any investigational agent within 4 weeks of Screening (Visit 1) or 5 half-lives of the investigational medicinal product (whichever is longer).
• 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.
• Subjects with known hypersensitivity to GKT137831 or its excipients (e.g. capsule "bulking" agents).
• A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin \< 10.0 g/dL (or 6.2 mmol/L).
• 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.
• 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).
• End-stage renal disease requiring dialysis.
• 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.
• Liver function tests (transaminases, alkaline phosphatase, direct and total bilirubin) \>3x upper limit of normal values

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Temple University: collaborator
• Tulane University: collaborator
• University of Michigan: collaborator

Study Sites (4)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Temple University Medical Center

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

setanaxib

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Steven R Duncan, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Model Details: Following screening assessments, IPF patients who meet all inclusion/exclusion criteria will be randomly assigned to receive one of the following treatments in a ratio of 1:1: • Arm A (n=30) - GKT137831 Treatment: GKT137831 will be administered orally, at a dose of 400 mg bid, for a total of 24 weeks. • Arm B (n=30) - Placebo Treatment: Arm B subjects will receive matching placebo for the same duration. Participants will be followed in face-to-face visits with trial personnel every 6 weeks for 24 weeks to assess drug effects and monitor safety during their treatments, and by phone surveillances one month thereafter.

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 7, 2019
• Study Start: September 7, 2020
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)