Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients
- Conditions
- Idiopathic Pulmonary Fibrosis
- Interventions
- Combination Product: EGCG 300 mg + NintedanibCombination Product: EGCG 600 mg + PirfenidoneCombination Product: Placebo 2 capsules + Nintedanib or PirfenidoneCombination Product: EGCG 600 mg + NintedanibCombination Product: EGCG 300 mg + PirfenidoneCombination Product: Placebo 4 capsules + Nintedanib or Pirfenidone
- Registration Number
- NCT05195918
- Lead Sponsor
- Hal Chapman
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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).
- 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.
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description EGCG 300 mg with Nintedanib EGCG 300 mg + Nintedanib Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Nintedanib for 12 weeks. EGCG 600 mg with Pirfenidone EGCG 600 mg + Pirfenidone 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 2 capsules + Nintedanib or Pirfenidone 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 EGCG 600 mg + Nintedanib Patients enrolled in this group will be given oral capsule EGCG 600 mg daily with doctor provided Nintedanib for 12 weeks. EGCG 300 mg with Pirfenidone EGCG 300 mg + Pirfenidone Patients 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 4 capsules + Nintedanib or Pirfenidone 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.
- Primary Outcome Measures
Name Time Method Participants with treatment-emergent adverse event (TEAE) Up to 12 weeks The number of participants with at least 1 treatment-emergent adverse event
The number of grade 3 or 4 treatment-emergent adverse events (TEAE) Up to 12 weeks The number of grade 3 or 4 treatment-emergent adverse events
Participants with serious adverse event (SAE) Up to 12 weeks The number of participants with at least 1 serious adverse event
Participants died due to adverse events (AE) within 4 weeks of discontinuation Up to 12 weeks The number of participants who died due to adverse events within 4 weeks of discontinuation from study treatment
Adverse events (AE) by causality Up to 12 weeks The number of adverse events by causality (reasonable possibility/no reasonable possibility)
Change in total score for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire 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 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
Participants with grade 3 or 4 treatment-emergent adverse events (TEAE) Up to 12 weeks The number of participants with at least 1 grade 3 or 4 treatment-emergent adverse events
Participants with discontinued study treatment due to serious adverse events (SAE) 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 Up to 12 weeks The number of participants who died due to adverse events on study treatment
Change in forced vital capacity (FVC) Up to 12 weeks Absolute and relative change in forced vital capacity from baseline at day 84
Participants with a peak level change for nintedanib or pirfenidone over 50% from screening to baseline (day 1) 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 trough level change for nintedanib or pirfenidone over 50% from baseline to day 14 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 an absolute change of at least 1.5 points for the LCQ 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
The number of treatment-emergent adverse events (TEAE) Up to 12 weeks The number of treatment-emergent adverse events
The number of serious adverse event (SAE) Up to 12 weeks The number of serious adverse events
Participants with discontinued study treatment due to adverse events (AE) Up to 12 weeks The number of participants who discontinued study treatment due to adverse events
Participants with adverse event (AE) by causality Up to 12 weeks The number of participants with at least 1 adverse event by causality (reasonable possibility/no reasonable possibility)
Change in forced vital capacity (FVC) % predicted 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) 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 Leicester Cough Questionnaire (LCQ) Up to 12 weeks Absolute change in total score for the Leicester Cough Questionnaire (LCQ) from baseline at day 84
Participants with peak (cmax) levels for EGCG < 250 nM at day 14 Day 14 The number of participants with peak (cmax) levels for EGCG \< 250 nM at day 14
Change in individual laboratory parameters Up to 12 weeks Absolute and relative change in individual laboratory parameters from baseline at day 84
Participants with a peak level change for nintedanib or pirfenidone over 50% from baseline to day 14 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
- Secondary Outcome Measures
Name Time Method Change of serum biomarker pro-MMP1 at day 84 Day 84 Change in level of serum biomarker pro-MMP1 from baseline at day 84
Change of serum biomarker COMP at day 14 Day 14 Change in level of serum biomarker COMP from baseline at day 14
Change of serum biomarker COMP at day 84 Day 84 Change in level of serum biomarker COMP from baseline at day 84
Change of serum biomarker Periostin at day 14 Day 14 Change in level of serum biomarker Periostin from baseline at day 14
Change of serum biomarker pro-MMP1 at day 14 Day 14 Change in level of serum biomarker pro-MMP1 from baseline at day 14
Change of serum biomarker Periostin at day 84 Day 84 Change in level of serum biomarker Periostin from baseline at day 84
Trial Locations
- Locations (7)
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Temple University
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
University of Washington
🇺🇸Seattle, Washington, United States
UCSF Parnassus
🇺🇸San Francisco, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States