Targeting Pro-Inflammatory Cells in Idiopathic Pulmonary Fibrosis: a Human Trial

NCT02874989 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00037000
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The study team hypothesizes that intermittent (3 doses administered over 3 consecutive days in 3 consecutive weeks) oral administration of combination Dasatinib (100 mg/d) + Quercetin (1250 mg/d) will be safe and well tolerated in patients with IPF. Treatment with D+Q will result in reduced abundance of pro-inflammatory cells within subjects over baseline. Finally, the reduction in biomarkers of cellular pro-inflammatory state will be related to no change in functional and patient reported outcomes.

Conditions

Idiopathic Pulmonary Fibrosis (IPF)

Outcome Measures

Primary Outcomes (29)

• Percentage of pro-inflammatory expressing cells

  A skin biopsy will be obtained at baseline and the percentage of pro-inflammatory expressing cells will be recorded

  baseline

• Percentage of pro-inflammatory expressing cells

  A skin biopsy will be obtained at 4 weeks post baseline/5 days after the last dose of study medication and the percentage of pro-inflammatory expressing cells will be recorded

  4 weeks post baseline visit biopsy/ 5 days post last dose study drug

• Blood Pressure

  screening 1 week pre baseline visit

• Blood Pressure

  baseline visit

• Blood Pressure

  4 weeks post baseline

• Weight

  screening 1 week pre baseline visit

• Weight

  baseline visit

• Weight

  4 weeks post baseline

• Heart Rate

  screening 1 week pre baseline visit

• Heart Rate

  baseline visit

• Heart Rate

  4 weeks post baseline

• CBC (complete blood count)

  screening 1 week pre baseline visit

• CBC (complete blood count)

  4 weeks post baseline

• Lipid Panel

  screening 1 week pre baseline visit

• Lipid Panel

  4 weeks post baseline

• HbA1c (glycated hemoglobin)

  screening 1 week pre baseline visit

• HbA1c (glycated hemoglobin)

  4 weeks post baseline

• CMP (comprehensive metabolic panel)

  screening 1 week pre baseline visit

• CMP (comprehensive metabolic panel)

  4 weeks post baseline

• Plasma hsCRP (high-sensitivity C-reactive protein)

  screening 1 week pre baseline visit

• Plasma hsCRP (high-sensitivity C-reactive protein)

  4 weeks post baseline

• Plasma IL-6 (inflammatory biomarker)

  baseline

• Plasma IL-6 (inflammatory biomarker)

  4 weeks post baseline

• Plasma IL-6R (inflammatory biomarker)

  baseline

• Plasma IL-6R (inflammatory biomarker)

  4 weeks post baseline

• Plasma PASP biomarkers (inflammatory biomarkers)

  baseline

• Plasma PASP biomarkers (inflammatory biomarkers)

  4 weeks post baseline

• p16INK4a biomarker (inflammatory biomarker)

  baseline

• p16INK4a biomarker (inflammatory biomarker)

  4 weeks post baseline

Study Arms (2)

Dasatinib + Quercetin

EXPERIMENTAL

Drug: Dasatinib + Quercetin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Dasatinib + Quercetin DRUG

Dasatinib + Quercetin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men between ages 50 and above, at the time of signing the informed consent.
• Post-menopausal women ages 50 and above, at the time of signing the informed consent. Note: Postmenopausal is defined as 12 months of spontaneous amenorrhea determined by self-report.
• A clinical diagnosis of IPF and characteristic chest HRCT scan (determined by panel of pulmonary radiologists) OR biopsy showing usual interstitial pneumonia (UIP).
• Body Mass Index (BMI) within the range 19 - 39.9 kg/ m2 (inclusive), where BMI = (weight in kg) / (height in meters)2 .
• Subjects participating in an exercise program must be willing to maintain their current activity level for the duration of the study period.
• Patients on stable therapy with nintedanib (Ofev) or pirfenidone (Esbriet) over the past 3 months.ORPatients not taking nintedanib (Ofev) or pirfenidone (Esbriet) may be enrolled if they have previously not tolerated one of those medications or if those medications have not yet been prescribed or used by the patient.
• Giving signed informed consent.
• No plans to travel over the next 6 weeks.

You may not qualify if:

• More than two moderate/severe IPF exacerbations within the past year Exacerbation is defined as worsening of two or more of the following major symptoms: dyspnea, sputum volume, sputum purulence OR worsening of any one major symptom together with at least one of the following additional symptoms: sore throat, colds (nasal discharge and/or nasal congestion), fever \> 37.5 ° C without any explained cause, increased cough, increase wheeze.
• A moderate exacerbation is defined as an event that is associated with a new prescription for antibiotics and/or oral steroids. A severe exacerbation is defined as an event that is associated with hospitalization or emergency room visit.
• Any moderate/severe IPF exacerbation within the past 4 weeks.
• History of a lung transplant.
• Use of anti-arrhythmic medications known to cause QTc prolongation.
• Pulmonary hypertension or cor pulmonale confirmed by echocardiography or heart catheterization.
• Myocardial infarction, angina, hospitalization for cardiac aetiology, stroke or transient ischemic attack in the past 6 months.
• Chronic heart failure.
• Neurologic, musculoskeletal, or other condition that in the opinion of the study physician limits subject's ability to complete study physical assessments.
• Uncontrolled diabetes (HbA1c \> 8% and fasting glucose \>200 mg/dL or the current use of insulin).
• Subjects with values outside the specified ranges for the following Key Clinical Laboratory Tests must be excluded from the study:
• Renal function: Glomerular Filtration Rate (GFR) \<30 (mL/min/1.73 m2) using formulae provided in the Study Reference Manual (SRM). Note: Subjects receiving dialysis are excluded from this study.
• ALT \>2xULN and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QTcB or QTcF \> 450 msec or QTc \> 480 msec in subjects with Bundle Branch Block based on a single ECG.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Mayo Clinic: collaborator
• The University of Texas Health Science Center at San Antonio: collaborator

Study Sites (2)

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78245, United States

Location

Related Publications (1)

• Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, Prata L, Masternak MM, Kritchevsky SB, Musi N, Kirkland JL. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. 2019 Feb;40:554-563. doi: 10.1016/j.ebiom.2018.12.052. Epub 2019 Jan 5.

  PMID: 30616998 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Dasatinib; Quercetin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stephen Kritchevsky, PhD

  Wake Forest Univerisity Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Some patients will be randomized either to placebo or study drug and other patients will go into open label.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2016
• First Posted: August 22, 2016
• Study Start: December 16, 2016
• Primary Completion: June 3, 2019
• Study Completion: June 3, 2019
• Last Updated: May 12, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)