GKT137831 in IPF Patients with Idiopathic Pulmonary Fibrosis

NCT ID: NCT03865927

Last Updated: 2024-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-07

Study Completion Date

2024-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Idiopathic Pulmonary Fibrosis

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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GKT137831

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

Group Type EXPERIMENTAL

GKT137831

Intervention Type DRUG

GKT137831 is a NOX enzyme inhibitor

Placebo Oral Tablet

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

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type OTHER

see Arm/Group description

Interventions

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Placebo Oral Tablet

see Arm/Group description

Intervention Type OTHER

GKT137831

GKT137831 is a NOX enzyme inhibitor

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Temple University

OTHER

Sponsor Role collaborator

Tulane University

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Steven R. Duncan, MD

PI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Steven R Duncan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Tulane University Medical Center

New Orleans, Louisiana, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Temple University Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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IRB-300001635

Identifier Type: -

Identifier Source: org_study_id