Collagen-targeted Positron Emission Tomography (PET) Imaging for Assessment of EGCG Effect

Collagen-targeted PET Imaging for Assessment of EGCG Effect

The primary purpose of this substudy is to determine if collagen-targeted PET using the type 1 collagen-targeted PET probe, Gallium-68 (68Ga)-labeled collagen binding probe 8 (CBP8) can inform as to drug effect of EGCG and assist in dose selection.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: EGCG 300 mg; Drug: EGCG 600 mg; Drug: Placebo for EGCG 300 mg; Drug: Placebo for EGCG 600 mg

Detailed Description

This is an optional sub-study of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, pharmacokinetic (PK) interactions with standard of care drugs, and biomarkers of drug effect." Up to twenty-two participants participating in the aforementioned study will be enrolled into this sub-study. This substudy will be conducted at a select number of sites with capabilities for performing [68Ga]CBP8 PET.

Eligible participants who consent to the substudy will undergo [68Ga]CBP8 PET-CT or [68Ga]CBP8 PET-MRI at two time points. Participants will undergo 68Ga-CBP8 PET within 7 days prior to randomization and then again within 7 days prior to day 84 of the phase I study.

The hypothesis is that [68Ga]CBP8 PET will detect decreased collagen deposition in individuals treated with EGCG compared to placebo.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Harold Chapman, MD; Phone Number: 415-514-1210; Email: hal.chapman@ucsf.edu
• Study Contact Backup: Name: Sydney Montesi, MD; Phone Number: 617-724-4030; Email: sbmontesi@mgb.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Caroline Fromson; Phone Number: 617-643-3260; Email: CFROMSON@MGH.HARVARD.EDU
      • Contact: Sydney Montesi, MD; Phone Number: 617-724-4030; Email: SBMONTESI@PARTNERS.ORG
      • Principal Investigator: Sydney Montesi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Enrolled in and eligible (based on screening procedures - Visit 1) for the main EGCG Phase 1 study, "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect
2. Signed informed consent

Exclusion Criteria:

1. Pregnant or breastfeeding (a negative quantitative serum human chorionic gonadotropin (hCG) pregnancy test is required for females having child-bearing potential before the participant can participate)*
2. Research-related radiation exposure exceeds 50 millisievert (mSv) in the prior 12 months
3. Determined by the investigator to be clinically unsuitable for the study

Additional exclusion criteria for participants undergoing PET-MRI:

1. Electrical implants such as cardiac pacemaker, defibrillator, or perfusion pump
2. Metallic or electric implants contraindicated for magnetic resonance-PET (MR-PET) scanning
3. Claustrophobic reactions
4. Estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 within the prior 30 days

5. Known allergy to gadolinium

   • Women of childbearing potential (WCBP) are defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if < 55 years or 12 months if ≥ 55 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EGCG 300 mg; Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided anti-fibrotic for 12 weeks.	Drug: EGCG 300 mg; Participants will be administered EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: EGCG Capsules with EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks.; Drug: EGCG 600 mg; Participants will be administered placebo for EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: EGCG Capsules with EGCG (at least 94% purity). 600 mg EGCG (4 capsules) taken orally daily for 12 weeks.
Placebo Comparator: Placebo for EGCG 300 mg; Patients enrolled in this group will be given oral capsule Placebo daily for 12 weeks with doctor provided anti-fibrotic. The number of placebo capsules will be equal to that of 300 mg EGCG.	Drug: Placebo for EGCG 300 mg; Participants will be administered placebo for EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: Placebo Placebo (2 capsules) taken orally daily for 12 weeks.; Drug: Placebo for EGCG 600 mg; Participants will be administered placebo for EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: Placebo Placebo (4 capsules) taken orally daily for 12 weeks.
Active Comparator: EGCG 600 mg; Patients enrolled in this group will be given oral capsule EGCG 600 mg daily with doctor provided anti-fibrotic for 12 weeks.	Drug: EGCG 300 mg; Participants will be administered EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: EGCG Capsules with EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks.; Drug: EGCG 600 mg; Participants will be administered placebo for EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: EGCG Capsules with EGCG (at least 94% purity). 600 mg EGCG (4 capsules) taken orally daily for 12 weeks.
Placebo Comparator: Placebo for EGCG 600 mg; Patients enrolled in this group will be given oral capsule Placebo daily for 12 weeks with doctor provided anti-fibrotic. The number of placebo capsules will be equal to that of 600 mg EGCG.	Drug: Placebo for EGCG 300 mg; Participants will be administered placebo for EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: Placebo Placebo (2 capsules) taken orally daily for 12 weeks.; Drug: Placebo for EGCG 600 mg; Participants will be administered placebo for EGCG as part of the phase I study: "Dose ranging study of oral epigallocatechin-3-gallate (EGCG) given daily for 12 weeks to patients with Idiopathic Pulmonary Fibrosis (IPF) evaluating safety, PK interactions with standard of care drugs, and biomarkers of drug effect."; Other Names: Dietary Supplement: Placebo Placebo (4 capsules) taken orally daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in collagen probe uptake over the entire lungs	Changes in lung collagen uptake will be measured using the PET probe [68]Ga-CBP8. Measurements will be made over the entire lungs using standardized uptake values.	From baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in peak enhancement over the entire lungs	Changes in peak enhancement will be measured using dynamic-contrast enhanced MRI. This exploratory outcome is only relevant for participants that undergo PET/MRI.	From baseline to 12 weeks
Change in the rate of contrast washin over the entire lungs	Changes in rate of contrast washin will be measured using dynamic-contrast enhanced MRI. This exploratory outcome is only relevant for participants that undergo PET/MRI.	From baseline to 12 weeks
Change in the area under the curve at 60 seconds over the entire lungs	Changes in the area under the curve at 60 seconds will be measured using dynamic-contrast enhanced MRI. This exploratory outcome is only relevant for participants that undergo PET/MRI.	From baseline to 12 weeks
Change in the full width at half maximum over the entire lungs	Changes in the full width at half maximum will be measured using dynamic-contrast enhanced MRI. This exploratory outcome is only relevant for participants that undergo PET/MRI.	From baseline to 12 weeks
Change in the rate of contrast washout over the entire lungs	Changes in the rate of contrast washout will be measured using dynamic-contrast enhanced MRI. This exploratory outcome is only relevant for participants that undergo PET/MRI.	From baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Hal Chapman
• Collaborators: Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI); University of Michigan; Cornell University
• Investigators: Principal Investigator: Fernando Martinez, MD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.
• Izquierdo-Garcia D, Desogere P, Fur ML, Shuvaev S, Zhou IY, Ramsay I, Lanuti M, Catalano OA, Catana C, Caravan P, Montesi SB. Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. J Nucl Med. 2023 May;64(5):775-781. doi: 10.2967/jnumed.122.264530. Epub 2022 Dec 8.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2024
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: Pro00060157; R33HL158540 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No