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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05195918
Recruitment Status : Recruiting
First Posted : January 19, 2022
Last Update Posted : February 6, 2024
Sponsor:
Collaborators:
University of Michigan
Cornell University
Massachusetts General Hospital
Temple University
University of Washington
Information provided by (Responsible Party):
Hal Chapman, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE December 2, 2021
First Posted Date  ICMJE January 19, 2022
Last Update Posted Date February 6, 2024
Actual Study Start Date  ICMJE August 24, 2023
Estimated Primary Completion Date March 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2023)
  • Participants with treatment-emergent adverse event (TEAE) [ Time Frame: Up to 12 weeks ]
    The number of participants with at least 1 treatment-emergent adverse event
  • The number of treatment-emergent adverse events (TEAE) [ Time Frame: Up to 12 weeks ]
    The number of treatment-emergent adverse events
  • Participants with grade 3 or 4 treatment-emergent adverse events (TEAE) [ Time Frame: Up to 12 weeks ]
    The number of participants with at least 1 grade 3 or 4 treatment-emergent adverse events
  • The number of grade 3 or 4 treatment-emergent adverse events (TEAE) [ Time Frame: Up to 12 weeks ]
    The number of grade 3 or 4 treatment-emergent adverse events
  • Participants with serious adverse event (SAE) [ Time Frame: Up to 12 weeks ]
    The number of participants with at least 1 serious adverse event
  • The number of serious adverse event (SAE) [ Time Frame: Up to 12 weeks ]
    The number of serious adverse events
  • Participants with discontinued study treatment due to adverse events (AE) [ Time Frame: Up to 12 weeks ]
    The number of participants who discontinued study treatment due to adverse events
  • Participants with discontinued study treatment due to serious adverse events (SAE) [ Time Frame: Up to 12 weeks ]
    The number of participants who discontinued study treatment due to serious adverse events
  • Participants died due to adverse events (AE) on study treatment [ Time Frame: Up to 12 weeks ]
    The number of participants who died due to adverse events on study treatment
  • Participants died due to adverse events (AE) within 4 weeks of discontinuation [ Time Frame: Up to 12 weeks ]
    The number of participants who died due to adverse events within 4 weeks of discontinuation from study treatment
  • Participants with adverse event (AE) by causality [ Time Frame: Up to 12 weeks ]
    The number of participants with at least 1 adverse event by causality (reasonable possibility/no reasonable possibility)
  • Adverse events (AE) by causality [ Time Frame: Up to 12 weeks ]
    The number of adverse events by causality (reasonable possibility/no reasonable possibility)
  • Change in individual laboratory parameters [ Time Frame: Up to 12 weeks ]
    Absolute and relative change in individual laboratory parameters from baseline at day 84
  • Change in forced vital capacity (FVC) [ Time Frame: Up to 12 weeks ]
    Absolute and relative change in forced vital capacity from baseline at day 84
  • Change in forced vital capacity (FVC) % predicted [ Time Frame: Up to 12 weeks ]
    Absolute and relative change in forced vital capacity % predicted from baseline at day 84
  • Change in diffusing capacity for carbon monoxide (DLCO) [ Time Frame: Up to 12 weeks ]
    Absolute and relative change in diffusing capacity for carbon monoxide uncorrected for hemoglobin from baseline at day 84
  • Change in total score for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire [ Time Frame: Up to 12 weeks ]
    Absolute change in total score for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from baseline at day 84
  • Participants with an absolute change in K-BILD of 5 points or more in either direction [ Time Frame: Up to 12 weeks ]
    The number of participants with an absolute change in K-BILD from baseline to day 84 of 5 points or more in either direction
  • Change in total score for the Leicester Cough Questionnaire (LCQ) [ Time Frame: Up to 12 weeks ]
    Absolute change in total score for the Leicester Cough Questionnaire (LCQ) from baseline at day 84
  • Participants with an absolute change of at least 1.5 points for the LCQ [ Time Frame: Up to 12 weeks ]
    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
  • Participants with a peak level change for nintedanib or pirfenidone over 50% from screening to baseline (day 1) [ Time Frame: 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
  • Participants with a peak level change for nintedanib or pirfenidone over 50% from baseline to day 14 [ Time Frame: 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
  • Participants with a trough level change for nintedanib or pirfenidone over 50% from baseline to day 14 [ Time Frame: 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
  • Participants with peak (cmax) levels for EGCG < 250 nM at day 14 [ Time Frame: Day 14 ]
    The number of participants with peak (cmax) levels for EGCG < 250 nM at day 14
Original Primary Outcome Measures  ICMJE
 (submitted: January 13, 2022)
  • Changes in total bilirubin [ Time Frame: Up to 12 weeks ]
    Changes in total bilirubin between the 3 groups.
  • Changes in ALT/AST [ Time Frame: Up to 12 weeks ]
    Changes in alanine aminotransferase / aspartate aminotransferase (ALT/AST) between the 3 groups.
  • Change in peak levels of Nintedanib [ Time Frame: Up to 12 weeks ]
    Change in peak (cmax) levels of Nintedanib between EGCG+Nintedanib and Placebo+Nintedanib groups.
  • Change in peak levels of Pirfenidone [ Time Frame: Up to 12 weeks ]
    Change in peak (cmax) levels of Pirfenidone between EGCG+Pirfenidone and Placebo+Pirfenidone groups.
  • Change in peak levels of EGCG [ Time Frame: Up to 12 weeks ]
    Change in peak (cmax) levels of EGCG between EGCG+Nintedanib and EGCG+Pirfenidone groups.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2022)
  • Change of serum biomarker COMP at day 14 [ Time Frame: Day 14 ]
    Change in level of serum biomarker COMP from baseline at day 14
  • Change of serum biomarker COMP at day 84 [ Time Frame: Day 84 ]
    Change in level of serum biomarker COMP from baseline at day 84
  • Change of serum biomarker Periostin at day 14 [ Time Frame: Day 14 ]
    Change in level of serum biomarker Periostin from baseline at day 14
  • Change of serum biomarker Periostin at day 84 [ Time Frame: Day 84 ]
    Change in level of serum biomarker Periostin from baseline at day 84
  • Change of serum biomarker pro-MMP1 at day 14 [ Time Frame: Day 14 ]
    Change in level of serum biomarker pro-MMP1 from baseline at day 14
  • Change of serum biomarker pro-MMP1 at day 84 [ Time Frame: Day 84 ]
    Change in level of serum biomarker pro-MMP1 from baseline at day 84
Original Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2022)
  • Change in serum biomarker COMP [ Time Frame: Up to 12 weeks ]
    Change in serum pro-fibrotic biomarker Cartilage Oligomeric Matrix Protein (COMP) between the 3 groups.
  • Change in serum biomarker Periostin [ Time Frame: Up to 12 weeks ]
    Change in serum pro-fibrotic biomarker Periostin between the 3 groups.
  • Change in serum biomarker pro-MMP1 [ Time Frame: Up to 12 weeks ]
    Change in serum biomarker pro-MMP1 between the 3 groups.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
There will be two stages in this multi-center, double-blind, placebo-controlled, dose-ranging Phase I study. Participants will first be randomized to one of the four groups to receive 300 mg EGCG or placebo with one of the standard of care drugs (nintedanib or pirfenidone) for 12 weeks and 4 weeks follow-up. Once all 25 subjects at stage one have completed the study, a staged safety analysis will occur prior to opening stage two study with a higher group dose of 600 mg EGCG.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
All participants will be on one of the standard of care drugs (nintedanib or pirfenidone) and blindly given EGCG or placebo.
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Pulmonary Fibrosis
Intervention  ICMJE
  • 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 Name: epigallocatechin-3-gallate + Ofev
  • 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 Name: epigallocatechin-3-gallate + Esbriet
  • 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 Name: Placebo + Ofev or Esbriet
  • 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 Name: epigallocatechin-3-gallate + Ofev
  • 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 Name: epigallocatechin-3-gallate + Esbriet
  • 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 Name: Placebo + Ofev or Esbriet
Study Arms  ICMJE
  • 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.
    Intervention: Combination Product: EGCG 300 mg + Nintedanib
  • 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.
    Intervention: Combination Product: EGCG 300 mg + Pirfenidone
  • 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.
    Intervention: Combination Product: Placebo 2 capsules + Nintedanib or Pirfenidone
  • 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.
    Intervention: Combination Product: EGCG 600 mg + Nintedanib
  • 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.
    Intervention: Combination Product: EGCG 600 mg + Pirfenidone
  • 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.
    Intervention: Combination Product: Placebo 4 capsules + Nintedanib or Pirfenidone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 13, 2022)		 50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2025
Estimated Primary Completion Date March 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ying Wei, MD 415-514-1209 ying.wei@ucsf.edu
Contact: Harold Chapman, MD 415-514-1210 hal.chapman@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05195918
Other Study ID Numbers  ICMJE 22-35979
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Hal Chapman, University of California, San Francisco
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hal Chapman
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • University of Michigan
  • Cornell University
  • Massachusetts General Hospital
  • Temple University
  • University of Washington
Investigators  ICMJE
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
PRS Account University of California, San Francisco
Verification Date February 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP