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

Sponsor
Hal Chapman (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05195918
Collaborator
University of Michigan (Other), Cornell University (Other), Massachusetts General Hospital (Other), Temple University (Other), University of Washington (Other)
50
Enrollment
3
Locations
6
Arms
30
Anticipated Duration (Months)
16.7
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated 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.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
Anticipated Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
Mar 31, 2025
Anticipated Study Completion Date :
Mar 31, 2025

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Placebo + Ofev or Esbriet

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Participants with treatment-emergent adverse event (TEAE) [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) [Up to 12 weeks]

      The number of treatment-emergent adverse events

    3. 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

    4. 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

    5. Participants with serious adverse event (SAE) [Up to 12 weeks]

      The number of participants with at least 1 serious adverse event

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

      The number of serious adverse events

    7. 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

    8. 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

    9. 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

    10. Participants died due to adverse events (AE) within 30 days of discontinuation [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 [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 [Up to 12 weeks]

      The number of adverse events by causality (reasonable possibility/no reasonable possibility)

    13. Change in individual laboratory parameters [Up to 12 weeks]

      Absolute and relative change in individual laboratory parameters from baseline at day 84

    14. Change in forced vital capacity (FVC) [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 [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) [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 [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 [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) [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 [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 [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 [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 [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 [Day 14]

      Change in level of serum biomarker COMP from baseline at day 14

    2. Change of serum biomarker COMP at day 84 [Day 84]

      Change in level of serum biomarker COMP from baseline at day 84

    3. Change of serum biomarker Periostin at day 14 [Day 14]

      Change in level of serum biomarker Periostin from baseline at day 14

    4. Change of serum biomarker Periostin at day 84 [Day 84]

      Change in level of serum biomarker Periostin from baseline at day 84

    5. Change of serum biomarker pro-MMP1 at day 14 [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 [Day 84]

      Change in level of serum biomarker pro-MMP1 from baseline at day 84

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSF Parnassus San Francisco California United States 94143
    2 Massachusetts General Hospital Boston Massachusetts United States 02114
    3 Cornell University New York New York United States 10065

    Sponsors and Collaborators

    • Hal Chapman
    • University of Michigan
    • Cornell University
    • Massachusetts General Hospital
    • Temple University
    • University of Washington

    Investigators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Hal Chapman, Professor, University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT05195918
    Other Study ID Numbers:
    • 20-30339
    First Posted:
    Jan 19, 2022
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Hal Chapman, Professor, University of California, San Francisco
    Idiopathic Pulmonary Fibrosis
    epigallocatechin-3-gallate
    EGCG
    Additional relevant MeSH terms:
    Pulmonary Fibrosis
    Idiopathic Pulmonary Fibrosis
    Fibrosis
    Pirfenidone
    Nintedanib
    Epigallocatechin gallate

    Study Results

    No Results Posted as of Aug 19, 2022