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| Name | Class |
|---|---|
| University of Michigan | OTHER |
| Cornell University | OTHER |
| Massachusetts General Hospital | OTHER |
| Temple University |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EGCG 300 mg + Nintedanib | Combination Product | Dietary Supplement: EGCG Capsules with Teavigo EGCG (at least 94% purity). 300 mg EGCG (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib |
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Harold Chapman, MD | University of California, San Francisco | Principal Investigator |
| Fernando J Martinez, MD | Cornell University | Principal Investigator |
| Sydney Montesi | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Parnassus | San Francisco | California | 94143 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28872461 | Background | 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. | |
| 27939076 | Background |
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| OTHER |
| University of Washington | OTHER |
| University of Virginia | OTHER |
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.
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All participants will be on one of the standard of care drugs (nintedanib or pirfenidone) and blindly given EGCG or placebo.
|
| 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. |
|
|
| EGCG 300 mg + Pirfenidone | Combination Product | 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 Pirfenidone | Combination Product | Dietary Supplement: Placebo Placebo (2 capsules) taken orally daily for 12 weeks. Drug: Nintedanib Drug: Pirfenidone |
|
|
| EGCG 600 mg + Nintedanib | Combination Product | 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 + Pirfenidone | Combination Product | 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 Pirfenidone | Combination Product | Dietary Supplement: Placebo Placebo (4 capsules) taken orally daily for 12 weeks. Drug: Nintedanib Drug: Pirfenidone |
|
|
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 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 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 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 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 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 |
| 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 |
| 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 |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Weill Cornell Medicine | New York | New York | 10065 | United States |
| Temple University | Philadelphia | Pennsylvania | 19140 | United States |
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| University of Washington | Seattle | Washington | 98195 | United States |
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| 25579378 | Background | Lacouture 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. |
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| 12376503 | Background | Lee 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. |
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| 32160670 | Result | Chapman HA, Wei Y, Montas G, Leong D, Golden JA, Trinh BN, Wolters PJ, Le Saux CJ, Jones KD, Hills NK, Foster E, Oldham JM, Linderholm AL, Kotak P, Decaris M, Turner S, Song JW. Reversal of TGFbeta1-Driven Profibrotic State in Patients with Pulmonary Fibrosis. N Engl J Med. 2020 Mar 12;382(11):1068-1070. doi: 10.1056/NEJMc1915189. No abstract available. |
| 33472968 | Result | Wei Y, Dong W, Jackson J, Ho TC, Le Saux CJ, Brumwell A, Li X, Klesney-Tait J, Cohen ML, Wolters PJ, Chapman HA. Blocking LOXL2 and TGFbeta1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis. Thorax. 2021 Jul;76(7):729-732. doi: 10.1136/thoraxjnl-2020-215745. Epub 2021 Jan 20. |
| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D011658 | Pulmonary Fibrosis |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C045651 | epigallocatechin gallate |
| C530716 | nintedanib |
| C093844 | pirfenidone |
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