We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Not yet recruiting
First Posted : January 19, 2022
Last Update Posted : November 15, 2022
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

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.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis 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 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
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
Official Title: 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
Estimated Study Start Date : March 1, 2023
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : March 31, 2025


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Placebo + Ofev or Esbriet




Primary Outcome Measures :
  1. 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

  2. The number of treatment-emergent adverse events (TEAE) [ Time Frame: Up to 12 weeks ]
    The number of treatment-emergent adverse events

  3. 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

  4. 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

  5. Participants with serious adverse event (SAE) [ Time Frame: Up to 12 weeks ]
    The number of participants with at least 1 serious adverse event

  6. The number of serious adverse event (SAE) [ Time Frame: Up to 12 weeks ]
    The number of serious adverse events

  7. 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

  8. 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

  9. 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

  10. Participants died due to adverse events (AE) within 30 days of discontinuation [ Time Frame: Up to 12 weeks ]
    The number of participants who died due to adverse events within 30 days of discontinuation from study treatment

  11. 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)

  12. Adverse events (AE) by causality [ Time Frame: Up to 12 weeks ]
    The number of adverse events by causality (reasonable possibility/no reasonable possibility)

  13. Change in individual laboratory parameters [ Time Frame: Up to 12 weeks ]
    Absolute and relative change in individual laboratory parameters from baseline at day 84

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. Participants with a peak level change for nintedanib or pirfenidone over 50% from baseline to day 1 [ Time Frame: Day 1 ]
    The number of participants with a change from baseline to day 1 in peak levels for nintedanib or pirfenidone of 50% or more in either direction

  22. 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

  23. 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


Secondary Outcome Measures :
  1. Change of serum biomarker COMP at day 14 [ Time Frame: Day 14 ]
    Change in level of serum biomarker COMP from baseline at day 14

  2. Change of serum biomarker COMP at day 84 [ Time Frame: Day 84 ]
    Change in level of serum biomarker COMP from baseline at day 84

  3. Change of serum biomarker Periostin at day 14 [ Time Frame: Day 14 ]
    Change in level of serum biomarker Periostin from baseline at day 14

  4. Change of serum biomarker Periostin at day 84 [ Time Frame: Day 84 ]
    Change in level of serum biomarker Periostin from baseline at day 84

  5. 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

  6. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 or pirfenidone 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 1).

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): NCT05195918


Contacts
Layout table for location contacts
Contact: Ying Wei, MD 415-514-1209 ying.wei@ucsf.edu
Contact: Harold Chapman, MD 415-514-1210 hal.chapman@ucsf.edu

Locations
Layout table for location information
United States, California
UCSF Parnassus
San Francisco, California, United States, 94143
Contact: Ying Wei, MD    415-514-1209    ying.wei@ucsf.edu   
Contact: Harold Chapman, MD    415-514-1210    hal.chapman@ucsf.edu   
Principal Investigator: Harold Chapman, MD         
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Contact: Sydney Montesi, MD    617-724-4030    SBMONTESI@PARTNERS.ORG   
Principal Investigator: Sydney Montesi, MD         
United States, New York
Cornell University
New York, New York, United States, 10065
Contact: Elizabeth Peters       elp2018@med.cornell.edu   
Contact: Fernando Martinez    646-962-2748    fjm2003@med.cornell.edu   
Principal Investigator: Fernando Martinez, MD         
Sponsors and Collaborators
Hal Chapman
University of Michigan
Cornell University
Massachusetts General Hospital
Temple University
University of Washington
Investigators
Layout table for investigator information
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 of Results:
Other Publications:

Layout table for additonal information
Responsible Party: Hal Chapman, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT05195918    
Other Study ID Numbers: 20-30339
First Posted: January 19, 2022    Key Record Dates
Last Update Posted: November 15, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hal Chapman, University of California, San Francisco:
Idiopathic Pulmonary Fibrosis
epigallocatechin-3-gallate
EGCG
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Pirfenidone
Nintedanib
Epigallocatechin gallate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antioxidants
Protective Agents
Antimutagenic Agents
Anticarcinogenic Agents
Neuroprotective Agents