Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.

NCT03928847 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 17-23008R01HL142265
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two part study. In the first part, the pharmacokinetic profile of Epigallocatechin-3-gallate (EGCG) in normal human volunteers given a single oral dose will be determined to set the dose for the second part of the study. In the second part of this study, lung biopsy fragments and urine samples from patients with interstitial lung disease treated with EGCG will be evaluated in biochemical assays and compared to samples from untreated control patients.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (6)

• EGCG PK Level in Healthy Volunteers

  EGCG plasma levels in healthy volunteers were measured at 0, 0.5, 2, and 4 hours after a single dose at 450 mg, 600 mg, or 750 mg dosage by liquid chromatography-mass spectrometry (LC-MS).

  0, 0.5, 2, 4 hours after EGCG

• Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients

  Change from baseline to day 14 in serum biomarkers associated with IPF, Cartilage Oligomeric Matrix Protein (COMP) measured by ELISA.

  Day 1 to day 14

• Change of Serum Biomarker Periostin Before and After EGCG Treatment in ILD Patients

  Change from baseline to day 14 in serum biomarkers associated with IPF, Periostin measured by ELISA.

  Day 1 to day 14

• Difference of Biomarker Snail1 Between EGCG-treated and Non-treated Patient Groups

  Levels of biomarker Snail1 in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups.

  14 days

• Difference of Biomarker Collagen I Between EGCG-treated and Non-treated Patient Groups

  Levels of biomarker Collagen I in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups.

  14 days

• Difference of Biomarker p-Smad3 Between EGCG-treated and Non-treated Patient Groups

  Levels of biomarker p-Smad3 in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups.

  14 days

Study Arms (5)

EGCG PK in healthy volunteers 450 mg

OTHER

Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

Drug: Epigallocatechin-3-gallate (EGCG)

EGCG PK in healthy volunteers 600 mg

OTHER

Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

Drug: Epigallocatechin-3-gallate (EGCG)

EGCG PK in healthy volunteers 750 mg

OTHER

Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

Drug: Epigallocatechin-3-gallate (EGCG)

No treatment control in ILD patients

NO INTERVENTION

Patients: not treated with EGCG

EGCG treatment in ILD patients

EXPERIMENTAL

Patients: 600 mg EGCG capsules once daily by mouth for two weeks

Drug: Epigallocatechin-3-gallate (EGCG)

Interventions

Epigallocatechin-3-gallate (EGCG) DRUG

Epigallocatechin-3-gallate (EGCG) capsules

Also known as: Teavigo

EGCG PK in healthy volunteers 450 mg; EGCG PK in healthy volunteers 600 mg; EGCG PK in healthy volunteers 750 mg; EGCG treatment in ILD patients

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1: healthy volunteers
• Part 2:
• study will consist of patients presenting to the UCSF interstitial lung disease (ILD) outpatient clinic with imaging indicative of lung fibrosis but of uncertain classification, and who are willing to take EGCG for a minimum of 2 weeks prior to surgery.

You may not qualify if:

• co-morbidities affect hepatic function, such as HCV infection, cirrhosis, or
• using drugs with significant hepatic toxicities

Sponsors & Collaborators

• Hal Chapman: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UC San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (2)

• 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.

  PMID: 33472968 BACKGROUND

• 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.

  PMID: 32160670 RESULT

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

epigallocatechin gallate

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was a pilot study with a small sample size.

Results Point of Contact

• Title: Harold A. Chapman, M.D.
• Organization: University of California at San Francisco

hal.chapman@ucsf.edu

415-514-1210

Study Officials

• Hal A Chapman, MD

  UC San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 26, 2019
• Study Start: December 1, 2017
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: December 22, 2022
• Results First Posted: December 22, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)