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GKT137831 in IPF Patients With Idiopathic Pulmonary Fibrosis (GKT137831)

Primary Purpose

Idiopathic Pulmonary Fibrosis

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo Oral Tablet

GKT137831

About this trial

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis focused on measuring Reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

University of Alabama at BirminghamRecruiting
Tulane University Medical CenterRecruiting
University of Michigan Medical CenterRecruiting
Temple University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GKT137831

Placebo Oral Tablet

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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

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.

Full Information

NCT ID

NCT03865927

First Posted

March 1, 2019

Last Updated

July 11, 2023

Sponsor

University of Alabama at Birmingham

Collaborators

Temple University, Tulane University, University of Michigan

1. Study Identification

Unique Protocol Identification Number

NCT03865927

Brief Title

GKT137831 in IPF Patients With Idiopathic Pulmonary Fibrosis

Acronym

GKT137831

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 7, 2020 (Actual)

Primary Completion Date

April 1, 2024 (Anticipated)

Study Completion Date

April 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Alabama at Birmingham

Collaborators

Temple University, Tulane University, University of Michigan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Idiopathic Pulmonary Fibrosis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GKT137831

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo Oral Tablet

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Other

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

see Arm/Group description

Intervention Type

Drug

Intervention Name(s)

GKT137831

Intervention Description

GKT137831 is a NOX enzyme inhibitor

Primary Outcome Measure Information:

Title

Surrogate biomarker of oxidative stress by mass spectroscopy

Description

Time Frame

From baseline thru week 24

Secondary Outcome Measure Information:

Title

Collagen degradation product by enzyme linked immunoabsorbant assay

Description

Time Frame

Baseline to week 24

Title

Pulmonary function by spirometry

Description

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.

Time Frame

Baseline to week 24

Title

Ambulatory ability by measuring walk distance in six minutes

Description

Six-minute walk distance (6MWD) will be compared at baseline and as changes from baseline among experimental arm participants and control subjects

Time Frame

Baseline to week 24

Title

Evaluation of safety by adverse events

Description

The number and severity of adverse events will be compared between experimental arm participants and those in the control arm.

Time Frame

Baseline to week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Steven R Duncan, MD

Phone

205-934-5018

srduncan@uabmc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven R Duncan, MD

Organizational Affiliation

University of Alabama at Birmingham

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Steven Duncan, MD

Facility Name

Tulane University Medical Center

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joseph Lasky, MD

Phone

504-988-5300

jlasky@tulane.edu

Facility Name

University of Michigan Medical Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kevin Flaherty, MD

Phone

734-936-4000

flaherty@med.umich.edu

Facility Name

Temple University Medical Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gerald Criner, MD

Phone

205-707-5864

gerard.criner@tuhs.temple.edu

12. IPD Sharing Statement

Learn more about this trial

GKT137831 in IPF Patients With Idiopathic Pulmonary Fibrosis

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