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NCT02177136: AESOP

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

Completed Phase 2 Results posted Last updated 8 July 2021
What this trial tests

Phase 2 trial testing Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC) in 77 participants. Completed in 22 March 2018.

Timeline
9 February 2015
Primary endpoint
7 March 2017
22 March 2018

Quick facts

Lead sponsorIntercept Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment77
Start date9 February 2015
Primary completion7 March 2017
Estimated completion22 March 2018
Sites36 locations across Italy, United States

Drugs / interventions tested

Conditions studied

Sponsor

Intercept Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Primary Sclerosing Cholangitis (PSC). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

DB Phase: Change From Baseline In Serum Alkaline Phosphatase (ALP) Primary · Baseline, Week 24

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.

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA-105.05± 38.02
5 mg OCA Titrating to 10 mg OCA-110.19± 33.77
Placebo-26.76± 36.65
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs) Primary · LTSE Baseline (DB Week 24) to Month 26

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. A

Dyslipidaemia
GroupValue95% CI
LTSE OCA Total1
Hepatic Disorder
GroupValue95% CI
LTSE OCA Total23
Pruritus
GroupValue95% CI
LTSE OCA Total34
DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT) Secondary · Baseline, Week 24

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.

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA-33.0-50.5 – 5.0
5 mg OCA Titrating to 10 mg OCA-5.5-30.0 – 4.5
Placebo-19.5-49.0 – 4.0
DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST) Secondary · Baseline, Week 24

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.

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA-8.0-20.0 – 19.0
5 mg OCA Titrating to 10 mg OCA0.5-17.5 – 32.8
Placebo-14.0-35.5 – 8.0
DB Phase: Change From Baseline In Serum Total Bilirubin Secondary · Baseline, Week 24

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.

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA0.8-1.7 – 4.3
5 mg OCA Titrating to 10 mg OCA1.3-1.3 – 6.9
Placebo0.0-5.1 – 4.3
DB Phase: Change From Baseline In Serum Direct Bilirubin Secondary · Baseline, Week 24

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.

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA0.8-0.9 – 0.9
5 mg OCA Titrating to 10 mg OCA0.9-0.9 – 6.4
Placebo0.0-1.7 – 4.3
DB Phase: Change From Baseline In Serum Gamma-glutamyl Transferase (GGT) Secondary · Baseline, Week 24

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.

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA-79.0-171.0 – -9.7
5 mg OCA Titrating to 10 mg OCA-78.5-235.5 – 14.0
Placebo-89.0-167.0 – 20.0
DB Phase: Change From Baseline In Plasma Fibroblast Growth Factor-19 (FGF-19) Secondary · Baseline, Week 24

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).

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA32.00-16.00 – 110.00
5 mg OCA Titrating to 10 mg OCA147.00-6.35 – 714.50
Placebo-19.50-79.56 – 28.00
DB Phase: Change From Baseline In Plasma 7α-Hydroxy-4-cholesten-3-one (C4) Secondary · Baseline, Week 24

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

GroupValue95% CI
1.5 mg OCA Titrating to 3 mg OCA-2.80-7.50 – 0.55
5 mg OCA Titrating to 10 mg OCA-2.90-6.94 – -1.12
Placebo0.05-2.25 – 10.84
LTSE Phase: Change From Baseline In Serum ALP At Month 12 Secondary · LTSE Baseline (DB Week 24), Month 12

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.

GroupValue95% CI
LTSE OCA Total-91.5-144.0 – -17.0
LTSE Phase: Change From Baseline In Serum ALT At Month 12 Secondary · LTSE Baseline (DB Week 24), Month 12

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.

GroupValue95% CI
LTSE OCA Total-37.0-60.5 – -7.5
LTSE Phase: Change From Baseline In Serum AST At Month 12 Secondary · LTSE Baseline (DB Week 24), Month 12

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.

GroupValue95% CI
LTSE OCA Total-14.5-30.5 – 9.5

Adverse events — posted to ClinicalTrials.gov

Time frame: DB Phase: From informed consent to end of double-blind phase study participation, up to 24 weeks. LTSE Phase: Baseline (DB Week 24) to Month 26.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1.5 mg OCA Titrating to 3 mg OCA
Serious: 4/25 (16%)
Deaths: 0/25
5 mg OCA Titrating to 10 mg OCA
Serious: 4/27 (15%)
Deaths: 0/27
Placebo
Serious: 2/24 (8%)
Deaths: 0/24
LTSE OCA Total
Serious: 19/59 (32%)
Deaths: 0/59

Serious adverse events (37 terms)

ReactionSystem1.5 mg OCA Titrating to 3 …5 mg OCA Titrating to 10 m…PlaceboLTSE OCA Total
Abdominal painGastrointestinal disorders
Bile duct stenosisHepatobiliary disorders
CholangitisHepatobiliary disorders
Cholangitis acuteHepatobiliary disorders
HyperbilirubinaemiaHepatobiliary disorders
Cholecystitis acuteHepatobiliary disorders
AscitesGastrointestinal disorders
PancreatitisGastrointestinal disorders
Oesophageal varices haemorrhageGastrointestinal disorders
Cholangitis infectiveInfections and infestations
PharyngitisInfections and infestations
Pneumonia bacterialInfections and infestations
Pseudomonal sepsisInfections and infestations
Oedema peripheralGeneral disorders
Peripheral swellingGeneral disorders
Abdominal pain upperGastrointestinal disorders
Colon dysplasiaGastrointestinal disorders
Crohn's diseaseGastrointestinal disorders
Gastric ulcerGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
PouchitisGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Bile duct obstructionHepatobiliary disorders
PeritonitisInfections and infestations
Abdominal abscessInfections and infestations
Other adverse events (47 terms — click to expand)

ReactionSystem1.5 mg OCA Titrating to 3 …5 mg OCA Titrating to 10 m…PlaceboLTSE OCA Total
PruritusSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
JaundiceHepatobiliary disorders
AscitesGastrointestinal disorders
ConstipationGastrointestinal disorders
Urinary tract infectionInfections and infestations
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders
FatigueGeneral disorders
Blood bilirubin increasedInvestigations
Colitis ulcerativeGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
CholangitisHepatobiliary disorders
BronchitisInfections and infestations
RashSkin and subcutaneous tissue disorders
Crohn's diseaseGastrointestinal disorders
SinusitisInfections and infestations
Oedema peripheralGeneral disorders
HyperbilirubinaemiaHepatobiliary disorders
Bile duct stenosisHepatobiliary disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Abdominal pain lowerGastrointestinal disorders
Varices oesophagealGastrointestinal disorders
Portal hypertensionHepatobiliary disorders
InfluenzaInfections and infestations
Alanine aminotransferase increasedInvestigations
Liver function test abnormalInvestigations
HypokalaemiaMetabolism and nutrition disorders
UrticariaSkin and subcutaneous tissue disorders
Abdominal distensionGastrointestinal disorders
Frequent bowel movementsGastrointestinal disorders
HeadacheNervous system disorders
DizzinessNervous system disorders

Most-reported serious reactions: Abdominal pain, Bile duct stenosis, Cholangitis, Cholangitis acute, Hyperbilirubinaemia, Cholecystitis acute, Ascites, Pancreatitis.

Data from ClinicalTrials.gov NCT02177136 adverse events section.

Sponsor's own description

This was a phase 2, double-blind (DB), placebo-controlled trial in participants with primary sclerosing cholangitis to evaluate the effect of obeticholic acid on liver biochemistry, in particular, serum alkaline phosphatase; and, safety. The long-term safety extension (LTSE) phase was conducted to evaluate the safety, tolerability, and efficacy of long-term, open-label use of OCA in participants with PSC who had completed the DB phase of the study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Primary Sclerosing Cholangitis.
    Lazaridis KN, LaRusso NF. · · 2016 · cited 348× · PMID 27653566 · DOI 10.1056/nejmra1506330
  2. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.
    Fleishman JS, Kumar S. · · 2024 · cited 267× · PMID 38664391 · DOI 10.1038/s41392-024-01811-6
  3. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis.
    Kowdley KV, Vuppalanchi R, Levy C, Floreani A, et al · · 2020 · cited 156× · PMID 32165251 · DOI 10.1016/j.jhep.2020.02.033
  4. Nuclear bile acid signaling through the farnesoid X receptor.
    Mazuy C, Helleboid A, Staels B, Lefebvre P. · · 2015 · cited 85× · PMID 25511198 · DOI 10.1007/s00018-014-1805-y
  5. Gut-liver axis signaling in portal hypertension.
    Simbrunner B, Mandorfer M, Trauner M, Reiberger T. · · 2019 · cited 82× · PMID 31660028 · DOI 10.3748/wjg.v25.i39.5897
  6. Clinical Advancements in the Targeted Therapies against Liver Fibrosis.
    Bansal R, Nagórniewicz B, Prakash J. · · 2016 · cited 72× · PMID 27999454 · DOI 10.1155/2016/7629724
  7. Review article: therapeutic aspects of bile acid signalling in the gut-liver axis.
    Simbrunner B, Trauner M, Reiberger T. · · 2021 · cited 63× · PMID 34555862 · DOI 10.1111/apt.16602
  8. Cholestatic liver diseases: new targets, new therapies.
    Santiago P, Scheinberg AR, Levy C. · · 2018 · cited 58× · PMID 30159035 · DOI 10.1177/1756284818787400

Verify or expand the search:

Other trials of Obeticholic Acid (OCA)

Trials testing the same drug.

Other recruiting trials for Primary Sclerosing Cholangitis (PSC)

Currently open trials in the same condition.

Other Intercept Pharmaceuticals trials

Trials by the same sponsor.

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