Trial Outcomes & Findings for Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC) (NCT NCT02177136)

Last Updated: 2021-07-08

Results Overview

The primary efficacy analysis compared the Week 24 change from Baseline in ALP between OCA treatment group and placebo using an analysis of covariance (ANCOVA) model with fixed effects for treatment group and randomization strata, and Baseline as a covariate. Results are reported in U/L.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2021-07-08

Participant Flow

Recruitment started December 2014 and completed September 2016. All participants were required to undergo thorough screening procedures, to confirm they met the eligibility criteria, during the 30-day period preceding the first dose.

Double-blind (DB) Phase: 77 participants were randomly allocated to treatment with placebo, 1.5 milligrams (mg) obeticholic acid (OCA) titrated to 3 mg OCA, or 5 mg OCA titrated to 10 mg OCA; however, 1 participant did not receive treatment. Long-term Safety Extension (LTSE): Open-label OCA doses up to 10 mg daily were evaluated.

Participant milestones

Participant milestones
Measure	1.5 mg OCA Titrating to 3 mg OCA Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks during the DB phase.	LTSE OCA Total Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.
DB Phase STARTED	26	26	25	0
DB Phase Received At Least 1 Dose Of Study Drug	25	26	25	0
DB Phase COMPLETED	19	21	21	0
DB Phase NOT COMPLETED	7	5	4	0
LTSE Phase STARTED	0	0	0	59
LTSE Phase Received At Least 1 Dose Of Study Drug	0	0	0	59
LTSE Phase COMPLETED	0	0	0	35
LTSE Phase NOT COMPLETED	0	0	0	24

Reasons for withdrawal

Reasons for withdrawal
Measure	1.5 mg OCA Titrating to 3 mg OCA Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks during the DB phase.	LTSE OCA Total Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.
DB Phase Withdrawal by Subject	2	0	0	0
DB Phase Discontinued Due to Pruritus	1	3	0	0
DB Phase Adverse Event	3	2	3	0
DB Phase Protocol Violation	0	0	1	0
DB Phase Withdrew Consent Prior to Dosing	1	0	0	0
LTSE Phase Withdrawal by Subject	0	0	0	6
LTSE Phase Adverse Event	0	0	0	10
LTSE Phase Discontinued Due to Pruritus	0	0	0	4
LTSE Phase Physician Decision	0	0	0	2
LTSE Phase Lost to Follow-up	0	0	0	1
LTSE Phase Participant Moved	0	0	0	1

Baseline Characteristics

Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo for 24 weeks.	Total n=76 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	23 Participants n=7 Participants	24 Participants n=5 Participants	71 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Age, Continuous	41.6 years STANDARD_DEVIATION 12.56 • n=5 Participants	44.9 years STANDARD_DEVIATION 14.28 • n=7 Participants	43.7 years STANDARD_DEVIATION 13.05 • n=5 Participants	43.4 years STANDARD_DEVIATION 13.22 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	14 Participants n=7 Participants	11 Participants n=5 Participants	35 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	41 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	24 Participants n=7 Participants	24 Participants n=5 Participants	71 Participants n=4 Participants
Ethnicity (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
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
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	65 Participants n=4 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
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
Alkaline phosphatase (ALP)	422.5 units/liter (U/L) STANDARD_DEVIATION 123.07 • n=5 Participants	428.5 units/liter (U/L) STANDARD_DEVIATION 178.19 • n=7 Participants	562.8 units/liter (U/L) STANDARD_DEVIATION 300.22 • n=5 Participants	470.7 units/liter (U/L) STANDARD_DEVIATION 220.20 • n=4 Participants
Total Bilirubin	16.3 micromoles (umol)/L STANDARD_DEVIATION 8.17 • n=5 Participants	19.4 micromoles (umol)/L STANDARD_DEVIATION 10.94 • n=7 Participants	20.9 micromoles (umol)/L STANDARD_DEVIATION 11.48 • n=5 Participants	18.9 micromoles (umol)/L STANDARD_DEVIATION 10.35 • n=4 Participants
Weight	74.5 kilograms (kg) STANDARD_DEVIATION 12.51 • n=5 Participants	73.6 kilograms (kg) STANDARD_DEVIATION 12.76 • n=7 Participants	73.0 kilograms (kg) STANDARD_DEVIATION 12.95 • n=5 Participants	73.7 kilograms (kg) STANDARD_DEVIATION 12.59 • n=4 Participants
Height	174.4 centimeter STANDARD_DEVIATION 8.95 • n=5 Participants	170.4 centimeter STANDARD_DEVIATION 11.61 • n=7 Participants	172.6 centimeter STANDARD_DEVIATION 10.70 • n=5 Participants	172.4 centimeter STANDARD_DEVIATION 10.49 • n=4 Participants
Body Mass Index	24.6 kg/meter squared STANDARD_DEVIATION 4.38 • n=5 Participants	25.3 kg/meter squared STANDARD_DEVIATION 3.74 • n=7 Participants	24.5 kg/meter squared STANDARD_DEVIATION 3.71 • n=5 Participants	24.8 kg/meter squared STANDARD_DEVIATION 3.92 • n=4 Participants
International Normalized Ratio (INR)	1.0 ratio STANDARD_DEVIATION 0.06 • n=5 Participants	1.0 ratio STANDARD_DEVIATION 0.10 • n=7 Participants	1.0 ratio STANDARD_DEVIATION 0.07 • n=5 Participants	1.0 ratio STANDARD_DEVIATION 0.08 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Serum Alkaline Phosphatase (ALP)	-105.05 U/L Standard Error 38.02	-110.19 U/L Standard Error 33.77	-26.76 U/L Standard Error 36.65

PRIMARY outcome

Timeframe: LTSE Baseline (DB Week 24) to Month 26

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase.

The primary safety analysis evaluated the effects of OCA treatment on AESIs of pruritus, hepatic disorders, and dyslipidemia. All adverse event (AE) summaries were restricted to treatment emergent AEs (TEAEs), which were defined as any AEs that newly appeared, increased in frequency, or worsened in severity following initiation of investigational product. Treatment-emergent pruritus was defined as any preferred term (PT) including "Prur-". Hepatic disorder AESIs were defined using specific Hepatic Disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) terms. AE lipid profile changes, defined in the Dyslipidemia SMQ, were reported. Verbatim terms were mapped to PTs and system organ classes (SOCs) using MedDRA version 17.1 for all AE summaries except those for hepatic disorder AESIs, which used MedDRA version 18.1. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=59 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs) Dyslipidaemia	1 Participants	—	—
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs) Hepatic Disorder	23 Participants	—	—
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs) Pruritus	34 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

As a marker of hepatic biochemistry and liver function, the median change in ALT from Baseline at Week 24 is reported. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT)	-33.0 U/L Interval -50.5 to 5.0	-5.5 U/L Interval -30.0 to 4.5	-19.5 U/L Interval -49.0 to 4.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

As a marker of hepatic biochemistry and liver function, the median change in AST from Baseline at Week 24 is reported. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST)	-8.0 U/L Interval -20.0 to 19.0	0.5 U/L Interval -17.5 to 32.8	-14.0 U/L Interval -35.5 to 8.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

As a marker of hepatic biochemistry and liver function, the median change in serum total bilirubin from Baseline at Week 24 is reported. Results are reported in umol/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Serum Total Bilirubin	0.8 umol/L Interval -1.7 to 4.3	1.3 umol/L Interval -1.3 to 6.9	0.0 umol/L Interval -5.1 to 4.3

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

As a marker of hepatic biochemistry and liver function, the median change in serum direct bilirubin from Baseline at Week 24 is reported. Results are reported in umol/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Serum Direct Bilirubin	0.8 umol/L Interval -0.9 to 0.9	0.9 umol/L Interval -0.9 to 6.4	0.0 umol/L Interval -1.7 to 4.3

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

As a marker of hepatic biochemistry and liver function, the median change in serum GGT from Baseline at Week 24 is reported. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Serum Gamma-glutamyl Transferase (GGT)	-79.0 U/L Interval -171.0 to -9.7	-78.5 U/L Interval -235.5 to 14.0	-89.0 U/L Interval -167.0 to 20.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

To assess farnesoid X receptor (FXR) activity, the change in FGF-19 from Baseline at Week 24 is reported. Results are reported in picograms/milliliter (pg/mL).

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Plasma Fibroblast Growth Factor-19 (FGF-19)	32.00 pg/mL Interval -16.0 to 110.0	147.00 pg/mL Interval -6.35 to 714.5	-19.50 pg/mL Interval -79.56 to 28.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

To assess FXR activity, the change in plasma C4 from Baseline at Week 24 is reported. Results are reported in nanograms (ng)/mL.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=25 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA n=26 Participants Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo n=25 Participants Participants randomized to placebo took placebo daily for 24 weeks.
DB Phase: Change From Baseline In Plasma 7α-Hydroxy-4-cholesten-3-one (C4)	-2.80 ng/mL Interval -7.5 to 0.55	-2.90 ng/mL Interval -6.94 to -1.12	0.05 ng/mL Interval -2.25 to 10.84

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

The median change in serum ALP from Baseline to the last available visit is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=34 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Serum ALP At Month 12	-91.5 U/L Interval -144.0 to -17.0	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in ALT from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Serum ALT At Month 12	-37.0 U/L Interval -60.5 to -7.5	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in AST from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Serum AST At Month 12	-14.5 U/L Interval -30.5 to 9.5	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in serum total bilirubin from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in umol/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=34 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Serum Total Bilirubin At Month 12	0.5 umol/L Interval -1.7 to 5.2	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in serum direct bilirubin from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in umol/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=34 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Serum Direct Bilirubin At Month 12	0.0 umol/L Interval -1.7 to 1.8	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in serum GGT from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=34 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Serum GGT At Month 12	-120.3 U/L Interval -238.0 to 39.0	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in albumin from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in grams (g)/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Albumin At Month 12	-0.5 g/L Interval -3.5 to 1.0	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic biochemistry and liver function, the median change in INR from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In INR At Month 12	0.0 Ratio Interval 0.0 to 0.1	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic inflammation and fibrosis, the median change in TE, as a measure of hepatic stiffness, from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in kilopascal (kPa).

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=29 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Transient Elastography (TE) At Month 12	1.8 kPa Interval -0.8 to 6.0	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

As a marker of hepatic inflammation and fibrosis, the change in ELF score from Baseline at Month 12 is reported. The ELF score and its components (hyaluronic acid \[HA\]; procollagen-3 N-terminal peptide \[P3NP\]; tissue inhibitor of metalloproteinase 1 \[TIMP-1\]) was calculated as follows: 2.278 + 0.851 x ln(HA (ng/mL)) + 0.751 x ln(P3NP (ng/mL)) + 0.394 x ln(TIMP-1 (ng/mL). The DB value at Week 24 was used as the Baseline. An increase in score indicates an improvement/worsening of symptoms.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=34 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Enhanced Liver Fibrosis (ELF) At Month 12	0.3 Units on a scale Interval 0.0 to 1.0	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

To assess FXR activity, the change in FGF-19 from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in pg/mL.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Plasma FGF-19 At Month 12	77.7 pg/mL Interval -37.0 to 194.0	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

To assess FXR activity, the change in plasma C4 from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in ng/mL.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Plasma C4 At Month 12	-3.8 ng/mL Interval -8.1 to -0.9	—	—

SECONDARY outcome

Timeframe: Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase.

To assess inflammatory bowel disease (IBD) activity, the number of participants experiencing ulcerative colitis remission at Month 12 is reported. Remission was defined as a partial Mayo score of ≤2 with no individual sub-score exceeding 1 point.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=59 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Participants Experiencing Ulcerative Colitis Remission At Month 12 Yes	16 participants	—	—
LTSE Phase: Participants Experiencing Ulcerative Colitis Remission At Month 12 No	0 participants	—	—

SECONDARY outcome

Timeframe: Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase.

To assess IBD activity, the number of participants experiencing Crohn's Disease remission at Month 12 is reported. Remission was defined as a Crohn's Disease Activity Index score of \<150.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=59 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Participants Experiencing Crohn's Disease Remission At Month 12 Yes	5 participants	—	—
LTSE Phase: Participants Experiencing Crohn's Disease Remission At Month 12 No	1 participants	—	—

SECONDARY outcome

Timeframe: Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

To assess the effects on bile acids, the median change in total bile acids from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in umol/L.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=35 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Total Bile Acids At Month 12	-1.59 umol/L Interval -8.12 to 6.49	—	—

SECONDARY outcome

Timeframe: LTSE Baseline (DB Week 24), Month 12

Population: LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

To assess the effects on disease-specific symptoms, the median change in the pruritus VAS score from Baseline at Month 12 is reported. The score is derived from the VAS participant questionnaire, which has the participant draw a line anywhere on a scale that best represents the severity of the itch; the scale ranges from 0 (no itching) to 10 (worst possible itching), in increments of 2. An increase in score represents an increase in severity of symptoms. The DB value at Week 24 was used as the Baseline.

Outcome measures

Outcome measures
Measure	1.5 mg OCA Titrating to 3 mg OCA n=37 Participants Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	5 mg OCA Titrating to 10 mg OCA Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Placebo Participants randomized to placebo took placebo daily for 24 weeks.
LTSE Phase: Change From Baseline In Pruritus Visual Analogue Scale (VAS) At Month 12	1.0 units on a scale Interval 0.0 to 20.0	—	—

Adverse Events

1.5 mg OCA Titrating to 3 mg OCA

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

5 mg OCA Titrating to 10 mg OCA

Serious events: 4 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

LTSE OCA Total

Serious events: 19 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information

Intercept Pharmaceuticals, Inc.

Phone: 844-782-4278

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigators must wait 18 months after the study ends to publish their results and a multi-center publication must come first. The sponsor has a 45-day review period with the option to extend to an additional 90 days.
Publication restrictions are in place

Restriction type: OTHER