Idiopathic Pulmonary FibrosisPhase 1NCT05195918
Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients
A Phase 1 study testing EGCG 300 mg + Nintedanib, EGCG 300 mg + Pirfenidone and EGCG 600 mg + Nintedanib in people with Idiopathic Pulmonary Fibrosis, run by Hal Chapman at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- EGCG 300 mg + Nintedanib, EGCG 300 mg + Pirfenidone and EGCG 600 mg + Nintedanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 7 sitesUnited States
- Study dates
- 24 Aug 2023to 19 Mar 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged 40-85 years old.
- Participant has IPF satisfying the 2022 ATS diagnostic criteria, confirmed by enrolling investigator at Visit 1.
- 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).
- Participant has a FVC ≥ 50% predicted using the global lung function initiative (GLI).
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- Participant has a DLCO corrected for hemoglobin ≥ 35% predicted using the GLI.
- 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.
- Participant has a life expectancy of at least 9 months at Visit 1.
- Ability to take oral medication and be willing to adhere to EGCG regimen.
- 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.
Who cannot join
- AST, ALT, or direct bilirubin above upper limit normal from any cause at the Screening Visit.
- Any history of HCV or HBV infection, NASH/NAFLD, or cirrhosis.
- Alcohol consumption greater than 7 drinks per week.
- Participant has emphysema ≥ 50% or the extent of emphysema is greater than the extent of fibrosis as per interpretation of Site Investigator or radiologist.
- Participant has received investigational therapy for IPF within 4 weeks before baseline (Visit 2).
- Participant is receiving systemic corticosteroids equivalent to prednisone > 10 mg/day or equivalent within 2 weeks of baseline visit (Visit 2).
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- 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.
- Participant has baseline resting oxygen saturation of < 89% on room air or need for continuous oxygen use at baseline visit (Visit 2).
- Consumption of GTE products in excess of a cup of green tea a day within one month of the baseline visit (Visit 2).
- Participant is receiving digoxin at the time of screening (Visit 1) and for the duration of the study.
- Active respiratory infection requiring treatment with antibiotics within 4 weeks of the baseline visit (Visit 2).
- Likely to be listed for transplant during trial participation.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan
Ann Arbor, Michigan, 48109
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Virginia
Charlottesville, Virginia, 22908
Weill Cornell Medicine
New York, New York, 10065
Temple University
Philadelphia, Pennsylvania, 19140
UCSF Parnassus
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
About this study
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
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.
Read the 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.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- EGCG 300 mg + Nintedanib, EGCG 300 mg + Pirfenidone, Placebo 2 capsules + Nintedanib or Pirfenidone, EGCG 600 mg + Nintedanib, EGCG 600 mg + Pirfenidone
- Keywords
- Idiopathic Pulmonary Fibrosis, epigallocatechin-3-gallate, EGCG
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGCG 300 mg + NintedanibCombination product
Also called epigallocatechin-3-gallate + Ofev
Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks.
Drug: Nintedanib
EGCG 300 mg + PirfenidoneCombination product
Also called epigallocatechin-3-gallate + Esbriet
Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks.
Drug: Pirfenidone
Placebo 2 capsules + Nintedanib or PirfenidoneCombination product
Also called Placebo + Ofev or Esbriet
Dietary Supplement: Placebo Placebo (2 capsules) taken orally daily for 12 weeks.
Drug: Nintedanib
Drug: Pirfenidone
EGCG 600 mg + NintedanibCombination product
Also called epigallocatechin-3-gallate + Ofev
Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 600 mg EGCG (2 capsules) taken orally daily for 12 weeks.
Drug: Nintedanib
EGCG 600 mg + PirfenidoneCombination product
Also called epigallocatechin-3-gallate + Esbriet
Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 600 mg EGCG (2 capsules) taken orally daily for 12 weeks.
Drug: Pirfenidone
Placebo 4 capsules + Nintedanib or PirfenidoneCombination product
Also called Placebo + Ofev or Esbriet
Dietary Supplement: Placebo Placebo (4 capsules) taken orally daily for 12 weeks.
Drug: Nintedanib
Drug: Pirfenidone
| Study group | Role | What they receive |
|---|---|---|
| EGCG 300 mg with Nintedanib | Active comparator | Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Nintedanib for 12 weeks. Receives: Combination Product: EGCG 300 mg + Nintedanib |
| EGCG 300 mg with Pirfenidone | Active comparator | Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks. Receives: Combination Product: EGCG 300 mg + Pirfenidone |
| Placebo for EGCG 300 mg | Placebo comparator | 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. Receives: Combination Product: Placebo 2 capsules + Nintedanib or Pirfenidone |
| EGCG 600 mg with Nintedanib | Active comparator | Patients enrolled in this group will be given oral capsule EGCG 600 mg daily with doctor provided Nintedanib for 12 weeks. Receives: Combination Product: EGCG 600 mg + Nintedanib |
| EGCG 600 mg with Pirfenidone | Active comparator | Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks. Receives: Combination Product: EGCG 600 mg + Pirfenidone |
| Placebo for EGCG 600 mg | Placebo comparator | 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. Receives: Combination Product: Placebo 4 capsules + Nintedanib or Pirfenidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants with treatment-emergent adverse event (TEAE)
The number of participants with at least 1 treatment-emergent adverse event
Measured: Up to 12 weeks
The number of treatment-emergent adverse events (TEAE)
The number of treatment-emergent adverse events
Measured: 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
Measured: 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
Measured: Up to 12 weeks
Participants with serious adverse event (SAE)
The number of participants with at least 1 serious adverse event
Measured: Up to 12 weeks
The number of serious adverse event (SAE)
The number of serious adverse events
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 12 weeks
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
Measured: 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)
Measured: Up to 12 weeks
Adverse events (AE) by causality
The number of adverse events by causality (reasonable possibility/no reasonable possibility)
Measured: Up to 12 weeks
Change in individual laboratory parameters
Absolute and relative change in individual laboratory parameters from baseline at day 84
Measured: Up to 12 weeks
Change in forced vital capacity (FVC)
Absolute and relative change in forced vital capacity from baseline at day 84
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1
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
Measured: Day 14
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
Measured: 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
Measured: Day 14
Secondary outcomes (6)
Change of serum biomarker COMP at day 14
Change in level of serum biomarker COMP from baseline at day 14
Measured: Day 14
Change of serum biomarker COMP at day 84
Change in level of serum biomarker COMP from baseline at day 84
Measured: Day 84
Change of serum biomarker Periostin at day 14
Change in level of serum biomarker Periostin from baseline at day 14
Measured: Day 14
Change of serum biomarker Periostin at day 84
Change in level of serum biomarker Periostin from baseline at day 84
Measured: Day 84
Change of serum biomarker pro-MMP1 at day 14
Change in level of serum biomarker pro-MMP1 from baseline at day 14
Measured: Day 14
Change of serum biomarker pro-MMP1 at day 84
Change in level of serum biomarker pro-MMP1 from baseline at day 84
Measured: Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start24 Aug 2023
- Primary completion19 Mar 2026
- Study completion19 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hal Chapman
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan, Cornell University, Massachusetts General Hospital, Temple University, University of Washington, University of Virginia
- Responsible party
- Sponsor-investigator, Hal Chapman, University of California, San Francisco
- Investigators
- Harold Chapman, MD, Principal investigator, University of California, San FranciscoFernando J Martinez, MD, Principal investigator, Cornell UniversitySydney Montesi, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05195918
- Sponsor's protocol ID
- 22-35979
- Status last verified
- Apr 2026
- First submitted
- 2 Dec 2021
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA. Fibroblast-specific inhibition of TGF-beta1 signaling attenuates lung and tumor fibrosis. J Clin Invest. 2017 Oct 2;127(10):3675-3688. doi: 10.1172/JCI94624. Epub 2017 Sep 5.
PubMed 28872461Raghu G, Brown KK, Collard HR, Cottin V, Gibson KF, Kaner RJ, Lederer DJ, Martinez FJ, Noble PW, Song JW, Wells AU, Whelan TP, Wuyts W, Moreau E, Patterson SD, Smith V, Bayly S, Chien JW, Gong Q, Zhang JJ, O'Riordan TG. Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial. Lancet Respir Med. 2017 Jan;5(1):22-32. doi: 10.1016/S2213-2600(16)30421-0. Epub 2016 Dec 7.
PubMed 27939076Hu J, Webster D, Cao J, Shao A. The safety of green tea and green tea extract consumption in adults - Results of a systematic review. Regul Toxicol Pharmacol. 2018 Jun;95:412-433. doi: 10.1016/j.yrtph.2018.03.019. Epub 2018 Mar 24.
PubMed 29580974Isomura T, Suzuki S, Origasa H, Hosono A, Suzuki M, Sawada T, Terao S, Muto Y, Koga T. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016 Nov;70(11):1221-1229. doi: 10.1038/ejcn.2016.78. Epub 2016 May 18.
PubMed 27188915Lancaster L, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, King TE Jr, Lederer DJ, Lin Z, Nathan SD, Pereira CA, Swigris JJ, Valeyre D, Noble PW. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. BMJ Open Respir Res. 2016 Jan 12;3(1):e000105. doi: 10.1136/bmjresp-2015-000105. eCollection 2016.
PubMed 26835133Corte T, Bonella F, Crestani B, Demedts MG, Richeldi L, Coeck C, Pelling K, Quaresma M, Lasky JA. Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis. Respir Res. 2015 Sep 24;16:116. doi: 10.1186/s12931-015-0276-5.
PubMed 26400368Li H, Chang HM, Shi Z, Leung PCK. ID3 mediates the TGF-beta1-induced suppression of matrix metalloproteinase-1 in human granulosa cells. FEBS J. 2019 Nov;286(21):4310-4327. doi: 10.1111/febs.14964. Epub 2019 Jun 28.
PubMed 31215762Sheppard D. Transforming growth factor beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc Am Thorac Soc. 2006 Jul;3(5):413-7. doi: 10.1513/pats.200601-008AW.
PubMed 16799084Principe DR, DeCant B, Mascarinas E, Wayne EA, Diaz AM, Akagi N, Hwang R, Pasche B, Dawson DW, Fang D, Bentrem DJ, Munshi HG, Jung B, Grippo PJ. TGFbeta Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis. Cancer Res. 2016 May 1;76(9):2525-39. doi: 10.1158/0008-5472.CAN-15-1293. Epub 2016 Mar 15.
PubMed 26980767Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337-45.
PubMed 3456347Akhurst RJ, Hata A. Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov. 2012 Oct;11(10):790-811. doi: 10.1038/nrd3810. Epub 2012 Sep 24.
PubMed 23000686Lacouture ME, Morris JC, Lawrence DP, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Berzofsky JA, Hsu FJ, Guitart J. Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immunother. 2015 Apr;64(4):437-46. doi: 10.1007/s00262-015-1653-0. Epub 2015 Jan 13.
PubMed 25579378Hu GX, Yao ST, Zeng LH, Peng YZ, Zheng J. Effects of hydroxycamptothecin on the expression of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of MMP-1, and type I collagen in rats with pulmonary fibrosis. Genet Mol Res. 2015 May 4;14(2):4625-32. doi: 10.4238/2015.May.4.21.
PubMed 25966236Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1025-32.
PubMed 12376503Li M, Krishnaveni MS, Li C, Zhou B, Xing Y, Banfalvi A, Li A, Lombardi V, Akbari O, Borok Z, Minoo P. Epithelium-specific deletion of TGF-beta receptor type II protects mice from bleomycin-induced pulmonary fibrosis. J Clin Invest. 2011 Jan;121(1):277-87. doi: 10.1172/JCI42090. Epub 2010 Dec 6.
PubMed 21135509
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05195918
- Acronym / sponsor ID
- 22-35979
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- Idiopathic Pulmonary Fibrosis, epigallocatechin-3-gallate, EGCG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Hal ChapmanUniversity, hospital or other
- Collaborators
- University of Michigan, Cornell University, Massachusetts General Hospital, Temple University, University of Washington, University of Virginia
- Study start
- 24 Aug 2023 (actual)
- Primary completion
- 19 Mar 2026 (actual)
- Study completion
- 19 Mar 2026 (actual)
- First posted
- 19 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- 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.
| Arm | Type | Receives |
|---|---|---|
| EGCG 300 mg with Nintedanib | Active comparator | Combination Product: EGCG 300 mg + NintedanibPatients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Nintedanib for 12 weeks. |
| EGCG 300 mg with Pirfenidone | Active comparator | Combination Product: EGCG 300 mg + PirfenidonePatients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks. |
| Placebo for EGCG 300 mg | Placebo comparator | Combination Product: Placebo 2 capsules + Nintedanib or PirfenidonePatients 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. |
| EGCG 600 mg with Nintedanib | Active comparator | Combination Product: EGCG 600 mg + NintedanibPatients enrolled in this group will be given oral capsule EGCG 600 mg daily with doctor provided Nintedanib for 12 weeks. |
| EGCG 600 mg with Pirfenidone | Active comparator | Combination Product: EGCG 600 mg + PirfenidonePatients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks. |
| Placebo for EGCG 600 mg | Placebo comparator | Combination Product: Placebo 4 capsules + Nintedanib or PirfenidonePatients 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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged 40-85 years old.
- Participant has IPF satisfying the 2022 ATS diagnostic criteria, confirmed by enrolling investigator at Visit 1.
- 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).
Key exclusion criteria (12 listed)
- AST, ALT, or direct bilirubin above upper limit normal from any cause at the Screening Visit.
- Any history of HCV or HBV infection, NASH/NAFLD, or cirrhosis.
- Alcohol consumption greater than 7 drinks per week.
- Participant has emphysema ≥ 50% or the extent of emphysema is greater than the extent of fibrosis as per interpretation of Site Investigator or radiologist.
- Participant has received investigational therapy for IPF within 4 weeks before baseline (Visit 2).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EGCG 300 mg + NintedanibAlso: epigallocatechin-3-gallate + OfevDietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib | Combination product | EGCG 300 mg with Nintedanib |
| EGCG 300 mg + PirfenidoneAlso: epigallocatechin-3-gallate + EsbrietDietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Pirfenidone | Combination product | EGCG 300 mg with Pirfenidone |
| Placebo 2 capsules + Nintedanib or PirfenidoneAlso: Placebo + Ofev or EsbrietDietary Supplement: Placebo Placebo (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib Drug: Pirfenidone | Combination product | Placebo for EGCG 300 mg |
| EGCG 600 mg + NintedanibAlso: epigallocatechin-3-gallate + OfevDietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 600 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib | Combination product | EGCG 600 mg with Nintedanib |
| EGCG 600 mg + PirfenidoneAlso: epigallocatechin-3-gallate + EsbrietDietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 600 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Pirfenidone | Combination product | EGCG 600 mg with Pirfenidone |
| Placebo 4 capsules + Nintedanib or PirfenidoneAlso: Placebo + Ofev or EsbrietDietary Supplement: Placebo Placebo (4 capsules) taken orally daily for 12 weeks. Drug: Nintedanib Drug: Pirfenidone | Combination product | Placebo for EGCG 600 mg |
Primary outcome
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
6 secondary outcomes
Change of serum biomarker COMP at day 14
Time frame: Day 14
Change of serum biomarker COMP at day 84
Time frame: Day 84
Change of serum biomarker Periostin at day 14
Time frame: Day 14
Change of serum biomarker Periostin at day 84
Time frame: Day 84
Change of serum biomarker pro-MMP1 at day 14
Time frame: Day 14
Change of serum biomarker pro-MMP1 at day 84
Time frame: Day 84
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
- Background: PubMed 28872461Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA. Fibroblast-specific inhibition of TGF-beta1 signaling attenuates lung and tumor fibrosis. J Clin Invest. 2017 Oct 2;127(10):3675-3688. doi: 10.1172/JCI94624. Epub 2017 Sep 5.
- Background: PubMed 27939076Raghu G, Brown KK, Collard HR, Cottin V, Gibson KF, Kaner RJ, Lederer DJ, Martinez FJ, Noble PW, Song JW, Wells AU, Whelan TP, Wuyts W, Moreau E, Patterson SD, Smith V, Bayly S, Chien JW, Gong Q, Zhang JJ, O'Riordan TG. Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial. Lancet Respir Med. 2017 Jan;5(1):22-32. doi: 10.1016/S2213-2600(16)30421-0. Epub 2016 Dec 7.
- Background: PubMed 29580974Hu J, Webster D, Cao J, Shao A. The safety of green tea and green tea extract consumption in adults - Results of a systematic review. Regul Toxicol Pharmacol. 2018 Jun;95:412-433. doi: 10.1016/j.yrtph.2018.03.019. Epub 2018 Mar 24.
- Background: PubMed 27188915Isomura T, Suzuki S, Origasa H, Hosono A, Suzuki M, Sawada T, Terao S, Muto Y, Koga T. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016 Nov;70(11):1221-1229. doi: 10.1038/ejcn.2016.78. Epub 2016 May 18.
- Background: PubMed 26835133Lancaster L, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, King TE Jr, Lederer DJ, Lin Z, Nathan SD, Pereira CA, Swigris JJ, Valeyre D, Noble PW. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. BMJ Open Respir Res. 2016 Jan 12;3(1):e000105. doi: 10.1136/bmjresp-2015-000105. eCollection 2016.
- Background: PubMed 26400368Corte T, Bonella F, Crestani B, Demedts MG, Richeldi L, Coeck C, Pelling K, Quaresma M, Lasky JA. Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis. Respir Res. 2015 Sep 24;16:116. doi: 10.1186/s12931-015-0276-5.
- Background: PubMed 31215762Li H, Chang HM, Shi Z, Leung PCK. ID3 mediates the TGF-beta1-induced suppression of matrix metalloproteinase-1 in human granulosa cells. FEBS J. 2019 Nov;286(21):4310-4327. doi: 10.1111/febs.14964. Epub 2019 Jun 28.
- Background: PubMed 16799084Sheppard D. Transforming growth factor beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc Am Thorac Soc. 2006 Jul;3(5):413-7. doi: 10.1513/pats.200601-008AW.
- Background: PubMed 26980767Principe DR, DeCant B, Mascarinas E, Wayne EA, Diaz AM, Akagi N, Hwang R, Pasche B, Dawson DW, Fang D, Bentrem DJ, Munshi HG, Jung B, Grippo PJ. TGFbeta Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis. Cancer Res. 2016 May 1;76(9):2525-39. doi: 10.1158/0008-5472.CAN-15-1293. Epub 2016 Mar 15.
- Background: PubMed 3456347Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337-45.
- Background: PubMed 23000686Akhurst RJ, Hata A. Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov. 2012 Oct;11(10):790-811. doi: 10.1038/nrd3810. Epub 2012 Sep 24.
- Background: PubMed 25579378Lacouture ME, Morris JC, Lawrence DP, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Berzofsky JA, Hsu FJ, Guitart J. Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immunother. 2015 Apr;64(4):437-46. doi: 10.1007/s00262-015-1653-0. Epub 2015 Jan 13.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harold Chapman, MD principal investigator
University of California, San Francisco
Fernando J Martinez, MD principal investigator
Cornell University
Sydney Montesi principal investigator
Massachusetts General Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EGCG 300 mg + Nintedanib, EGCG 300 mg + Pirfenidone and EGCG 600 mg + Nintedanib in people with Idiopathic Pulmonary Fibrosis, run by Hal Chapman at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants with treatment-emergent adverse event (TEAE) (time frame: Up to 12 weeks). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05195918, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.