Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients

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

The primary purpose of this multi-center, double-blind, placebo-controlled, dose-ranging Phase I study is to assess the safety of a purified from green tea, EGCG, in patients with idiopathic pulmonary fibrosis (IPF) as a potential novel treatment for pulmonary fibrosis.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Combination product: EGCG 300 mg + Nintedanib; Combination product: EGCG 300 mg + Pirfenidone; Combination product: Placebo 2 capsules + Nintedanib or Pirfenidone; Combination product: EGCG 600 mg + Nintedanib; Combination product: EGCG 600 mg + Pirfenidone; Combination product: Placebo 4 capsules + Nintedanib or Pirfenidone

Detailed Description

This is a multi-center, double-blind, placebo-controlled, dose-ranging Phase I study of once daily EGCG administered for 12 weeks. The study will assess safety, pharmacokinetics, and biomarker measurements of drug effect in IPF patients already receiving background therapy for IPF with either nintedanib or pirfenidone. Two different doses of EGCG will be studied.

The rationale for this study is 1) extensive pre-clinical data in mice that EGCG is efficacious in attenuating pulmonary fibrosis by blocking collagen cross-linking and the pro-fibrotic pathway mediated by TGFβ1 signaling and 2) recently published data demonstrating that in humans EGCG is safe and capable of blocking lung tissue pro-fibrotic signaling when given two weeks prior to diagnostic surgical biopsy of pulmonary fibrosis patients, many of whom were subsequently diagnosed with IPF.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ying Wei, MD; Phone Number: 415-514-1209; Email: ying.wei@ucsf.edu
• Study Contact Backup: Name: Harold Chapman, MD; Phone Number: 415-514-1210; Email: hal.chapman@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Parnassus
      • Contact: Ying Wei, MD; Phone Number: 415-514-1209; Email: ying.wei@ucsf.edu
      • Contact: Harold Chapman, MD; Phone Number: 415-514-1210; Email: hal.chapman@ucsf.edu
      • Principal Investigator: Harold Chapman, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Sydney Montesi, MD; Phone Number: 617-724-4030; Email: SBMONTESI@PARTNERS.ORG
      • Principal Investigator: Sydney Montesi, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Cornell University
      • Contact: Elizabeth Peters; Email: elp2018@med.cornell.edu
      • Contact: Fernando Martinez; Phone Number: 646-962-2748; Email: fjm2003@med.cornell.edu
      • Principal Investigator: Fernando Martinez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female, aged 40-85 years old.
4. Participant has IPF satisfying the 2022 ATS diagnostic criteria, confirmed by enrolling investigator at Visit 1.
5. Participant must have been on a stable dose of nintedanib twice daily or pirfenidone three times daily dose for at least 12 weeks prior to baseline (Visit 2).
6. Participant has a FVC ≥ 50% predicted using the global lung function initiative (GLI).
7. Participant has a DLCO corrected for hemoglobin ≥ 35% predicted using the GLI.
8. Women of child bearing potential (WCBP), 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, must have a negative serum pregnancy test within 1 week prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception include use of oral contraceptives or Depo-Provera, with an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence.
9. Participant has a life expectancy of at least 9 months at Visit 1.
10. Ability to take oral medication and be willing to adhere to EGCG regimen.
11. Agreement to refrain from drinking green tea in excess of a cup a day or eating green tea extract for 4 weeks before baseline and during the trial.

Exclusion Criteria:

1. AST, ALT, or direct bilirubin above upper limit normal from any cause at the Screening Visit.
2. Any history of HCV or HBV infection, NASH/NAFLD, or cirrhosis.
3. Alcohol consumption greater than 7 drinks per week.
4. Participant has emphysema ≥ 50% or the extent of emphysema is greater than the extent of fibrosis as per interpretation of Site Investigator or radiologist.
5. Participant has received investigational therapy for IPF within 4 weeks before baseline (Visit 2).
6. Participant is receiving systemic corticosteroids equivalent to prednisone > 10 mg/day or equivalent within 2 weeks of baseline visit (Visit 2).
7. Participant has any concurrent condition other than IPF that, in the Investigator's opinion, is unstable and/or would impact the likelihood of survival for the study duration or the participant's ability to complete the study as designed, or may influence any of the safety or efficacy assessments included in the study.
8. Participant has baseline resting oxygen saturation of < 89% on room air or need for continuous oxygen use at baseline visit (Visit 2).
9. Consumption of GTE products in excess of a cup of green tea a day within one month of the baseline visit (Visit 2).
10. Participant is receiving digoxin at the time of screening (Visit 1) and for the duration of the study.
11. Active respiratory infection requiring treatment with antibiotics within 4 weeks of the baseline visit (Visit 2).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EGCG 300 mg with Nintedanib; Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Nintedanib for 12 weeks.	Combination product: EGCG 300 mg + Nintedanib; Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib; Other Names: epigallocatechin-3-gallate + Ofev
Active Comparator: EGCG 300 mg with Pirfenidone; Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks.	Combination product: EGCG 300 mg + Pirfenidone; Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Pirfenidone; Other Names: epigallocatechin-3-gallate + Esbriet
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 Nintedanib or Pirfenidone. The number of placebo capsules will be equal to that of 300 mg EGCG.	Combination product: Placebo 2 capsules + Nintedanib or Pirfenidone; Dietary Supplement: Placebo Placebo (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib Drug: Pirfenidone; Other Names: Placebo + Ofev or Esbriet
Active Comparator: EGCG 600 mg with Nintedanib; Patients enrolled in this group will be given oral capsule EGCG 600 mg daily with doctor provided Nintedanib for 12 weeks.	Combination product: EGCG 600 mg + Nintedanib; Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 600 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib; Other Names: epigallocatechin-3-gallate + Ofev
Active Comparator: EGCG 600 mg with Pirfenidone; Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks.	Combination product: EGCG 600 mg + Pirfenidone; Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 600 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Pirfenidone; Other Names: epigallocatechin-3-gallate + Esbriet
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 Nintedanib or Pirfenidone. The number of placebo capsules will be equal to that of 600 mg EGCG.	Combination product: Placebo 4 capsules + Nintedanib or Pirfenidone; Dietary Supplement: Placebo Placebo (4 capsules) taken orally daily for 12 weeks. Drug: Nintedanib Drug: Pirfenidone; Other Names: Placebo + Ofev or Esbriet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with treatment-emergent adverse event (TEAE)	The number of participants with at least 1 treatment-emergent adverse event	Up to 12 weeks
The number of treatment-emergent adverse events (TEAE)	The number of treatment-emergent adverse events	Up to 12 weeks
Participants with grade 3 or 4 treatment-emergent adverse events (TEAE)	The number of participants with at least 1 grade 3 or 4 treatment-emergent adverse events	Up to 12 weeks
The number of grade 3 or 4 treatment-emergent adverse events (TEAE)	The number of grade 3 or 4 treatment-emergent adverse events	Up to 12 weeks
Participants with serious adverse event (SAE)	The number of participants with at least 1 serious adverse event	Up to 12 weeks
The number of serious adverse event (SAE)	The number of serious adverse events	Up to 12 weeks
Participants with discontinued study treatment due to adverse events (AE)	The number of participants who discontinued study treatment due to adverse events	Up to 12 weeks
Participants with discontinued study treatment due to serious adverse events (SAE)	The number of participants who discontinued study treatment due to serious adverse events	Up to 12 weeks
Participants died due to adverse events (AE) on study treatment	The number of participants who died due to adverse events on study treatment	Up to 12 weeks
Participants with adverse event (AE) by causality	The number of participants with at least 1 adverse event by causality (reasonable possibility/no reasonable possibility)	Up to 12 weeks
Adverse events (AE) by causality	The number of adverse events by causality (reasonable possibility/no reasonable possibility)	Up to 12 weeks
Change in individual laboratory parameters	Absolute and relative change in individual laboratory parameters from baseline at day 84	Up to 12 weeks
Change in forced vital capacity (FVC)	Absolute and relative change in forced vital capacity from baseline at day 84	Up to 12 weeks
Change in forced vital capacity (FVC) % predicted	Absolute and relative change in forced vital capacity % predicted from baseline at day 84	Up to 12 weeks
Change in diffusing capacity for carbon monoxide (DLCO)	Absolute and relative change in diffusing capacity for carbon monoxide uncorrected for hemoglobin from baseline at day 84	Up to 12 weeks
Change in total score for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire	Absolute change in total score for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from baseline at day 84	Up to 12 weeks
Participants with an absolute change in K-BILD of 5 points or more in either direction	The number of participants with an absolute change in K-BILD from baseline to day 84 of 5 points or more in either direction	Up to 12 weeks
Change in total score for the Leicester Cough Questionnaire (LCQ)	Absolute change in total score for the Leicester Cough Questionnaire (LCQ) from baseline at day 84	Up to 12 weeks
Participants with an absolute change of at least 1.5 points for the LCQ	The number of participants with an absolute change from baseline to day 84 of 1.5 points or more in either direction for the LCQ	Up to 12 weeks
Participants with a peak level change for nintedanib or pirfenidone over 50% from baseline to day 14	The number of participants with a change from baseline to day 14 in peak levels for nintedanib or pirfenidone of 50% or more in either direction	Day 14
Participants with peak (cmax) levels for EGCG < 250 nM at day 14	The number of participants with peak (cmax) levels for EGCG < 250 nM at day 14	Day 14
Participants died due to adverse events (AE) within 4 weeks of discontinuation	The number of participants who died due to adverse events within 4 weeks of discontinuation from study treatment	Up to 12 weeks
Participants with a peak level change for nintedanib or pirfenidone over 50% from screening to baseline (day 1)	The number of participants with a change from screening to baseline (day 1) in peak levels for nintedanib or pirfenidone of 50% or more in either direction	Day 1
Participants with a trough level change for nintedanib or pirfenidone over 50% from baseline to day 14	The number of participants with a change from baseline to day 14 in trough levels for nintedanib or pirfenidone of 50% or more in either direction	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of serum biomarker COMP at day 14	Change in level of serum biomarker COMP from baseline at day 14	Day 14
Change of serum biomarker COMP at day 84	Change in level of serum biomarker COMP from baseline at day 84	Day 84
Change of serum biomarker Periostin at day 14	Change in level of serum biomarker Periostin from baseline at day 14	Day 14
Change of serum biomarker Periostin at day 84	Change in level of serum biomarker Periostin from baseline at day 84	Day 84
Change of serum biomarker pro-MMP1 at day 14	Change in level of serum biomarker pro-MMP1 from baseline at day 14	Day 14
Change of serum biomarker pro-MMP1 at day 84	Change in level of serum biomarker pro-MMP1 from baseline at day 84	Day 84

Collaborators and Investigators

• Sponsor: Hal Chapman
• Collaborators: Massachusetts General Hospital; University of Michigan; University of Washington; Temple University; Cornell University
• Investigators: Principal Investigator: Harold Chapman, MD, University of California, San Francisco; Principal Investigator: Fernando J Martinez, MD, Cornell University; Principal Investigator: Sydney Montesi, Massachusetts General Hospital

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 19, 2022

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; EGCG; epigallocatechin-3-gallate
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Protein Kinase Inhibitors; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Pirfenidone; Nintedanib; Epigallocatechin gallate
• Other Study ID Numbers: 22-35979

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