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Detection of Integrin avb6 in IPF, PSC, and COVID19 Using PET/CT

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ClinicalTrials.gov Identifier: NCT03183570
Recruitment Status : Recruiting
First Posted : June 12, 2017
Last Update Posted : November 27, 2020
Sponsor:
Collaborator:
Pliant Therapeutics, Inc.
Information provided by (Responsible Party):
Haiwei Henry Guo, Stanford University

Brief Summary:
Detection of Integrin avb6 in Idiopathic Pulmonary Fibrosis, Primary Sclerosing Cholangitis, and Coronavirus Disease 2019 with [18F]FP-R01-MG-F2 with PET/CT

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Primary Sclerosing Cholangitis Covid19 Pneumonia Drug: [18F]FP-R01-MG-F2 Early Phase 1

Detailed Description:

Stanford University has developed a new PET tracer, [18F]FP-R01-MG-F2, that selectively binds to integrin avb6, a cell surface receptor that is overexpressed in idiopathic pulmonary fibrosis (IPF). Increased avb6 receptors on IPF lung tissue has been well documented, while its expression remains relatively non-existent in the healthy adult lung.

The PET tracer's application will be expanded in primary sclerosing cholangitis (PSC) and COVID-19 pneumonia. The integrin avb6 is also up-regulated in the biliary epithelial cells, which drive the progression of biliary tree strictures and liver fibrosis through activation of TGF-b, as shown in IPF. Similarly, COVID-19 pneumonia is caused by the SARS-CoV-2 and leads to acute lung injury and integrin avb6 up-regulation.

The selected PET tracer [18F]FP-R01-MG-F2 has shown promise in identifying integrin avb6 in both preclinical and clinical studies at Stanford University. The investigators have demonstrated low [18F]FP-R01-MG-F2 radiopharmaceutical uptake in the heart and lung region of healthy volunteers, which was an expected biodistribution (the normal tissue uptake of the radiopharmaceutical within the body) based on immunohistochemical staining of healthy lung tissue, which demonstrated the presence of minimal avb6 receptors in healthy lung tissue.

OBJECTIVE:

  1. Exploring the use of the investigational radiopharmaceutical [18]FFP-R01-MG-F2 as a biomarker for avb6 integrin in fibrotic lung tissue.
  2. Exploring the use of the investigational radiopharmaceutical [18]FFP-R01-MG-F2 to access inflammation and fibrosis in the bile duct and liver.
  3. Exploring the use of the investigational radiopharmaceutical [18]FFP-R01-MG-F2 to assess lung injury in COVID-19 pneumonia.

The performance of [18F]FP-R01-MG-F2 PET/CT will be assessed in a cohort of up to 13-15 IPF patients, 5 PSC patients, 5 COVID19 pneumonia patients, and 5 age-matched healthy controls. Feasibility will be measured by drawing regions of interest (ROI) around the lung/ liver of participants with IPF, COVID19, or PSC, respectively, and the lungs of healthy adult volunteers and comparing the calculated standardized uptake value maximum(s) (SUV max).

The tracer's biodistribution, safety, and tolerability will also be studied.

Recruitment of IPF subjects and healthy volunteers has been completed, although recruitment for other aspects of this clinical trial is ongoing.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Detection of Integrin avb6 in Idiopathic Pulmonary Fibrosis, Primary Sclerosing Cholangitis, and Coronavirus Disease 2019 With [18F]FP-R01-MG-F2 With PET/CT
Actual Study Start Date : November 8, 2017
Estimated Primary Completion Date : April 14, 2022
Estimated Study Completion Date : April 14, 2023


Arm Intervention/treatment
Experimental: [18F]FP-R01-MG-F2 PET/CT in IPF Patients, Recovered COVID19 Patients, and Healthy Volunteers

Arm1: 7mCi (range 6-9 mCi) [18F]FP-R01-MG-F2 will be administered to the study participant. A 60-minute dynamic PET/CT scan to the center of the lungs in the FOV is followed by two vertex-to-thigh PET/CT scans.

NOTE: If the patient cannot tolerate lying down for an extended period of time at the time of imaging, the patient may be switched to scanning protocol Option B, which does not include an initial 60-minute dynamic PET/CT scan.

IPF Patients will have a repeat [18F]FP-R01-MG-F2 PET/CT scan performed within 3-8 weeks post initial scan (within 12-24 months post initial scan for previously scanned IPF patients if they are willing to be re-consented).

Drug: [18F]FP-R01-MG-F2
7mCi (range 6-9mCi) [18F]FP-R01-MG-F2 will be administered

Experimental: [18F]FP-R01-MG-F2 PET/CT in PSC Patients

Arm 2: 7mCi (range 6-9 mCi) [18F]FP-R01-MG-F2 will be administered to the study participant. A 60-minute dynamic PET/CT scan to the center of the liver in the FOV is followed by two vertex-to-thigh PET/CT scans.

A repeat [18F]FP-R01-MG-F2 PET/CT scan will be performed within 3-8 weeks post initial scan if a signal is present in the first scan.

Drug: [18F]FP-R01-MG-F2
7mCi (range 6-9mCi) [18F]FP-R01-MG-F2 will be administered

Experimental: [18F]FP-R01-MG-F2 PET/CT in actively infected COVID19 Patients
Arm 3: 7mCi (range 6-9 mCi) [18F]FP-R01-MG-F2 will be administered to the study participant. One vertex-to-thigh PET/CT scans to the center of the lung in the FOV will follow approximately 60 min post-injection.
Drug: [18F]FP-R01-MG-F2
7mCi (range 6-9mCi) [18F]FP-R01-MG-F2 will be administered




Primary Outcome Measures :
  1. SUV max comparison : IPF versus Healthy Lung, PSC versus Healthy Liver, COVID19 versus Healthy Lung [ Time Frame: an estimated average of 2 hours ]
    The SUVmax in a lung or liver with known IPF, COVID19 pneumonia, or PSC respectively will be compared to the SUVmax in a known healthy lung/liver. It is expected that the SUV max, which is a measurement of the maximum value of radiopharmaceutical uptake within the region of interest (ROI) in IPF, COVID19 pneumonia, and PSC will be higher than the SUV max in the healthy lung/liver.


Secondary Outcome Measures :
  1. Time Activity Measurements [ Time Frame: an estimated average of 1 hours ]
    Blood samples for blood time-activity measurements taken at 1, 3, 5, 10, 30, and 60 minutes after tracer injection for tracer kinetic analysis. Tracer kinetic analysis shows radiopharmaceutical distribution from the blood to the tissues over time.

  2. Incidence of Study Completion (Safety and Tolerability) [ Time Frame: an estimated average of 2 hours ]
    EKG data, vital signs and laboratory data collected before IV injection of [18F]FP-R01-MG-F2 and after completion of the scan will allow the investigators to evaluate the safety and tolerability of the radiopharmaceutical. This will be measured as the number of patients who successfully completed the study.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

1.0 Eligibility Criteria for IPF Patients

1.1 Inclusion Criteria

The following inclusion criteria will be monitored:

  • Patient is >/= 18 years old
  • Patient is capable of making an informed decision regarding his/her treatment
  • Patient diagnosed with IPF by a pulmonologist according to ATS guidelines
  • Patient has high-resolution CT with definite Usual Interstitial Pneumonia (UIP) pattern
  • Patient has PFT's within the last 12 months with:

    • FVC<85% predicted
    • DLCO<65% predicted
  • FEV1/FCV ratio >70%
  • Patient is able to comply with study procedures

    • Scanning Option A (60 +20 +20 mins) OR
    • Scanning Option B (8 +8 mins)

1.2 Exclusion Criteria

The following exclusion criteria will be monitored:

  • Patient with a serious uncontrolled concurrent medical illness that would limit compliance with study requirements
  • Patient has a history of any clinically significant lung disease other than IPF as determined by a pulmonologist
  • Patient has had a lung infection of any kind in the last 3 months
  • Patient is pregnant or lactating

2.0 Eligibility Criteria for PSC Patients

2.1 Inclusion Criteria

The following inclusion criteria will be monitored:

  • Patient is >/= 18 years old
  • Patient is capable of making an informed decision regarding his/her treatment
  • Patient diagnosed with large duct PSC, based on an abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous transhepatic cholangiopancreatography (PTC) in the context of cholestatic liver chemistry
  • Patient is able to comply with study procedures

    • Scanning Option C (60 +20+ 20 mins)

2.2 Exclusion Criteria

The following exclusion criteria will be monitored:

  • Patient with a serious uncontrolled concurrent medical illness that would limit compliance with study requirements
  • Patient has other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically
  • Patient has a history of ascending cholangitis within 60 days of screening, as assessed clinically
  • Patient has history, current clinical or radiological suspicion, or diagnosis of cholangiocarcinoma, other hepatobiliary malignancy, colorectal cancer, or other abdominal malignancy at any time
  • Presence of a percutaneous drain or bile duct stent
  • Patient is pregnant or lactating

3.0 Eligibility Criteria for Healthy Controls

3.1 Inclusion Criteria

The following inclusion criteria will be monitored:

  • Person is >/= 45 years old
  • Person is capable of making an informed decision regarding his/her treatment
  • Person is able to comply with study procedures

    • Scanning Option A (60 + 20 + 20 mins) OR
    • Scanning Option B (8 + 8 mins)

3.2 Exclusion Criteria

The following exclusion criteria will be monitored:

  • Person with a serious uncontrolled concurrent medical illness that would limit compliance with study requirements
  • Person has a history of any clinically significant lung disease other than IPF as determined by a pulmonologist
  • Person had lung infection of any kind in the last 3 months
  • Person is pregnant or lactating

4.0 Eligibility Criteria for COVID-19 patients

4.1 Inclusion Criteria

The following inclusion criteria will be monitored:

  • Patient is >/= 18 years old
  • Patient is capable of making an informed decision regarding his/her treatment
  • Patient with a history of SARS-CoV-2 (active or recovered) infection, based on positive RT-PCR testing
  • Recovered COVID-19 patient must show evidence of being non-infectious (per Stanford guideline):

    • Symptomatic, non-immunocompromised outpatients are considered COVID neg after 10 days or 3 days after symptoms resolve, whichever is longer.
    • Severely symptomatic or is immunocompromised outpatients are considered non-infectious after 20 days.
    • or RT-PCR negative x2, spaced >24 hrs apart
  • Patient shows or has shown evidence of pulmonary opacities as visualized on chest radiograph or CT
  • Patient is able to comply with study procedures and infection control instructions

    • Recovered COVID 19 patients: Scanning Option A (60 + 20 + 20 mins) OR
    • Recovered COVID-19 patients: Scanning Option B (8 + 8 mins)
    • COVID-19 patients with active infection or no evidence of non-active infection: Scanning Option D (8 mins)

4.2 Exclusion Criteria

The following exclusion criteria will be monitored:

  • Person with serious uncontrolled concurrent medical illness, such as severe hypoxia, that would limit compliance with study and infection control requirements
  • Person with pre-existing fibrosing lung disease (such as but not limited to IPF, NSIP, HP, and sarcoidosis prior to COVID-19 infection).
  • Person is pregnant or lactating

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03183570


Contacts
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Contact: Andrea Otte, DPT (650) 736-4183 anotte@stanford.edu

Locations
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United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Andrea Otte, DPT    650-736-4183    anotte@stanford.edu   
Sub-Investigator: Joshua Mooney, MD, MS         
Sub-Investigator: Tushar Desai, MD, MPH         
Principal Investigator: Henry Guo, MD, PhD         
Sub-Investigator: Aparna Goel, MD         
Sub-Investigator: Aruna Subramanian, MD         
Sub-Investigator: Andrei Iagaru, MD         
Sub-Investigator: Guido A Davidzon, MD, MS         
Sub-Investigator: Farshad Moradi, MD, PhD         
Sub-Investigator: Benjamin L Franc, MD, MBA         
Sub-Investigator: Carina Marie-Aparici, MD         
Sub-Investigator: Judy Nguyen, MD         
Sponsors and Collaborators
Stanford University
Pliant Therapeutics, Inc.
Investigators
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Study Director: Henry Guo, MD, PhD Stanford University
Additional Information:
Publications of Results:
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Responsible Party: Haiwei Henry Guo, Clinical Associate Professor, Stanford University
ClinicalTrials.gov Identifier: NCT03183570    
Other Study ID Numbers: IRB Protocol: 40450
First Posted: June 12, 2017    Key Record Dates
Last Update Posted: November 27, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangitis
Cholangitis, Sclerosing
Pneumonia
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases