Trial Outcomes & Findings for Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis. (NCT NCT03928847)

Last Updated: 2022-12-22

Results Overview

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).

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

35 participants

Primary outcome timeframe

0, 0.5, 2, 4 hours after EGCG

Results posted on

2022-12-22

Participant Flow

Healthy volunteer recruitment started in 12/1/2017 and ended in 3/30/2018. Subjects were recruited from UCSF community. Advertisements were posted around the campus. Patients recruitment started in 6/1/2018 and ended in 12/20/2018. Subjects were recruited from UCSF and UC Davis ILD clinics.

Participant milestones

Participant milestones
Measure	EGCG PK in Healthy Volunteers 450 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth (3 capsules)	EGCG PK in Healthy Volunteers 600 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth (3 capsules)	EGCG PK in Healthy Volunteers 750 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth (3 capsules)	No Treatment Control in ILD Patients None EGCG treated control ILD patients	EGCG Treatment in ILD Patients Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Patients: 600 mg EGCG capsules once daily by mouth for two weeks (4 capsules once daily)
Overall Study STARTED	5	5	5	10	10
Overall Study COMPLETED	5	5	5	10	10
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EGCG PK in Healthy Volunteers 450 mg n=5 Participants Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Epigallocatechin-3-gallate (EGCG): 3 EGCG capsules	EGCG PK in Healthy Volunteers 600 mg n=5 Participants Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Epigallocatechin-3-gallate (EGCG): 4 EGCG capsules	EGCG PK in Healthy Volunteers 750 mg n=5 Participants Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Epigallocatechin-3-gallate (EGCG): 5 EGCG capsules	No Treatment Control in ILD Patients n=10 Participants ILD patients that were not treated with EGCG are used as controls.	EGCG Treatment in ILD Patients n=10 Participants Patients: 600 mg EGCG capsules once daily by mouth for two weeks Epigallocatechin-3-gallate (EGCG): 4 EGCG capsules	Total n=35 Participants Total of all reporting groups
Age, Customized	64 years n=5 Participants	62 years n=7 Participants	68 years n=5 Participants	64 years n=4 Participants	65 years n=21 Participants	64 years n=8 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	6 Participants n=21 Participants	20 Participants n=8 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	4 Participants n=21 Participants	15 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	1 Participants n=21 Participants	12 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	9 Participants n=21 Participants	23 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Region of Enrollment United States	5 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	6 participants n=4 Participants	10 participants n=21 Participants	31 participants n=8 Participants
Region of Enrollment South Korea	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants	0 participants n=21 Participants	4 participants n=8 Participants
High-resolution computed tomography (HRCT) imaging indicative of lung fibrosis	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants	10 Participants n=21 Participants	20 Participants n=8 Participants

PRIMARY outcome

Timeframe: 0, 0.5, 2, 4 hours after EGCG

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).

Outcome measures

Outcome measures
Measure	EGCG PK in Healthy Volunteers 450 mg n=5 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	ECGC PK in Healthy Volunteers 600 mg n=5 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	EGCG PK in Healthy Volunteers 750 mg n=5 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
EGCG PK Level in Healthy Volunteers 0 hour after EGCG	NA nM Standard Deviation NA below the level of detection	NA nM Standard Deviation NA below the level of detection	NA nM Standard Deviation NA below the level of detection
EGCG PK Level in Healthy Volunteers 0.5 hour after EGCG	861 nM Standard Deviation 761	612 nM Standard Deviation 531	3126 nM Standard Deviation 4159
EGCG PK Level in Healthy Volunteers 2 hours after EGCG	1136 nM Standard Deviation 666	2266 nM Standard Deviation 2174	1582 nM Standard Deviation 536
EGCG PK Level in Healthy Volunteers 4 hours after EGCG	659 nM Standard Deviation 640	741 nM Standard Deviation 226	702 nM Standard Deviation 293

PRIMARY outcome

Timeframe: Day 1 to day 14

Population: Serum biomarker COMP was measured by ELISA and compared before and after EGCG treatment.

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

Outcome measures

Outcome measures
Measure	EGCG PK in Healthy Volunteers 450 mg n=10 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	ECGC PK in Healthy Volunteers 600 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	EGCG PK in Healthy Volunteers 750 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients Before EGCG treatment	137.2 ng/ml Standard Deviation 53.8	—	—
Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients After EGCG treatment	97.9 ng/ml Standard Deviation 26.9	—	—

PRIMARY outcome

Timeframe: Day 1 to day 14

Population: Serum biomarker Periostin was measured by ELISA and compared before and after EGCG treatment.

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

Outcome measures

Outcome measures
Measure	EGCG PK in Healthy Volunteers 450 mg n=10 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	ECGC PK in Healthy Volunteers 600 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	EGCG PK in Healthy Volunteers 750 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Change of Serum Biomarker Periostin Before and After EGCG Treatment in ILD Patients After EGCG treatment	35.2 ng/ml Standard Deviation 11.7	—	—
Change of Serum Biomarker Periostin Before and After EGCG Treatment in ILD Patients Before EGCG treatment	41.9 ng/ml Standard Deviation 15.9	—	—

PRIMARY outcome

Timeframe: 14 days

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.

Outcome measures

Outcome measures
Measure	EGCG PK in Healthy Volunteers 450 mg n=10 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	ECGC PK in Healthy Volunteers 600 mg n=10 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	EGCG PK in Healthy Volunteers 750 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Difference of Biomarker Snail1 Between EGCG-treated and Non-treated Patient Groups	0.825 percentage of reference sample Standard Deviation 0.332	0.132 percentage of reference sample Standard Deviation 0.098	—

PRIMARY outcome

Timeframe: 14 days

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.

Outcome measures

Outcome measures
Measure	EGCG PK in Healthy Volunteers 450 mg n=10 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	ECGC PK in Healthy Volunteers 600 mg n=10 Participants Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth	EGCG PK in Healthy Volunteers 750 mg Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Difference of Biomarker Collagen I Between EGCG-treated and Non-treated Patient Groups	0.894 percentage of reference sample Standard Deviation 0.375	0.136 percentage of reference sample Standard Deviation 0.058	—

PRIMARY outcome

Timeframe: 14 days

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.