Clinical trial NCT03865927: GKT137831 in IPF Patients with Idiopathic Pulmonary Fibrosis
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of GKT137831 in Patients with Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Reactive oxygen species (ROS)
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Temple University
name: Tulane University
name: University of Michigan
First posted: 2019-03-07
Enrollment: 58
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Surrogate biomarker of oxidative stress by mass spectroscopy
timeFrame: From baseline thru week 24
Secondary outcomes:
measure: Collagen degradation product by enzyme linked immunoabsorbant assay
timeFrame: Baseline to week 24
measure: Pulmonary function by spirometry
timeFrame: Baseline to week 24
measure: Ambulatory ability by measuring walk distance in six minutes
timeFrame: Baseline to week 24
measure: Evaluation of safety by adverse events
timeFrame: Baseline to week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Philadelphia
country: United States
facility: Temple University Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Alabama at Birmingham
name: Steven R Duncan, MD
role: PRINCIPAL_INVESTIGATOR
References: