Primary Biliary CirrhosisPhase 3POISENCT01473524
Phase 3 Study of Obeticholic Acid in Patients With Primary Biliary Cirrhosis
A Phase 3 study testing Obeticholic Acid (OCA) in people with Primary Biliary Cirrhosis, run by Intercept Pharmaceuticals at 59 sites in 13 countries.
Trial summary
The main objectives of the study were to assess the effects of Obeticholic Acid (OCA) on serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint and on safety in participants with primary biliary cirrhosis (PBC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- Obeticholic Acid (OCA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 217 participants
- Where
- 59 sitesin 13 countries
- Study dates
- Jan 2012to 17 Dec 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:
- History of elevated alkaline phosphatase (ALP) levels for at least 6 months
- Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (pyruvate dehydrogenase complex-E2 [PDC-E2], 2-oxo-glutaric acid dehydrogenase complex)
- Liver biopsy consistent with PBC
- At least 1 of the following qualifying biochemistry values:
- ALP ≥ 1.67x upper limit of normal (ULN)
Show all 16Show fewer
- Total bilirubin > ULN but < 2x ULN
- Age ≥ 18 years
- Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0.
- Contraception: Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and for 30 days after the end of treatment (EOT) visit. Effective methods of contraception are considered to be:
- Hormonal (for example, contraceptive pill, patch, intramuscular implant or injection); or
- Double barrier method, that is, (a) condom (male or female) or (b) diaphragm, with spermicide; or
- Intrauterine device (IUD); or
- Vasectomy (partner); or
- Sexual abstinence
- Must provide written informed consent and agree to comply with the trial protocol.
Who cannot join
- History or presence of other concomitant liver diseases including:
- Hepatitis C virus (HCV) infection; participants with active hepatitis B (HBV) infection will be excluded, however, participants who have seroconverted (hepatitis B surface antigen [Hbs Ag] and hepatitis B e antigen [Hbe Ag] negative) may be included after consultation with the medical monitor.
- Primary sclerosing cholangitis (PSC)
- Alcoholic liver disease
- Definite autoimmune liver disease or overlap hepatitis
- Nonalcoholic steatohepatitis (NASH)
Show all 29Show fewer
- Gilbert's Syndrome (due to interpretability of bilirubin levels)
- Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
- History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15
- Portal hypertension with complications, including: known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds or related therapeutic or prophylactic interventions (for example, beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt [TIPS]), or hepatic encephalopathy
- Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN
- Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/deciliter dL) (178 micromole [µmol])/liter [L])
- Participants with severe pruritus or those requiring systemic treatment for pruritus (for example, with bile acid sequestrants [BAS] or rifampicin) within 2 months of Day 0 will be excluded
- Administration of the following medications is prohibited as specified below:
- Prohibited 6 months prior to Day 0 and throughout the trial (that is, to last dose and/or EOT): azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)
- Prohibited 12 months prior to Day 0 and throughout the trial (that is, to last dose and/or EOT): antibodies or immunotherapy directed against interleukins or other cytokines or chemokines
- Participants who have previously participated in a clinical trial of OCA will not be allowed to participate
- History or presence of clinically concerning cardiac arrhythmias likely to affect survival during the trial, or prolongation of Screening (pretreatment) QT or QTc interval of > 500 milliseconds (msec)
- If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
- Known history of human immunodeficiency virus (HIV) infection
- Presence of any other disease or condition that is interfering with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine. Participants with inflammatory bowel disease or who have undergone gastric bypass procedures will be excluded (gastric lap band is acceptable).
- Medical conditions that may cause nonhepatic increases in ALP (for example, Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers (except carcinomas in situ or other stable, relatively benign conditions such as chronic lymphatic leukemia)
- Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the trial
- Anticipated changes to current concomitant medications during the course of the trial
- History of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (that is, the equivalent of fourteen 4-ounce (125 mL) glasses of wine or fourteen 12 ounce cans/bottles of beer), or other substance abuse within 1 year prior to Day 0
- Participation in another investigational drug, biologic, or medical device trial within 30 days prior to Screening
- History of noncompliance with medical regimens, or participants who are considered to be potentially unreliable
- Blood or plasma donation within 30 days prior to Day 0
- Mental instability or incompetence, such that the validity of informed consent or compliance with the trial is uncertain
Trial locations and contacts
59 sites in 13 countries.
59 sites in 13 countries
United States15 sites
University of Colorado, Denver
Aurora, Colorado, 80045
University of Chicago
Chicago, Illinois, 60637
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Henry Ford Health System
Detroit, Michigan, 48377
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Beth Israel Medical Center
New York, New York, 10003
Liver Institute of Virginia
Newport News, Virginia, 23602
Liver Institute of Virginia
Richmond, Virginia, 23226
Virginia Commonwealth University/McGuire DVAMC
Richmond, Virginia, 23249
UC Davis Medical Center
Sacramento, California, 95817
Scripps Clinic
San Diego, California, 92037
Swedish Medical Center
Seattle, Washington, 98101
St. Louis University
St Louis, Missouri, 63104
Germany10 sites
Universitätsklinikum Aachen
Aachen, D-52074
Friedrich-Alexander-Universität Erlangen
Erlangen, D-91054
Klinikum der Johann-Wolfgang Goethe Universität Frankfurt am Main
Frankfurt am Main, 60590
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, D-30625
Medizinische Universitätsklinik
Heidelberg, D-69120
Gastroenterologische Gemeinschaftspraxis, Dres. Felten / Hartmann / Hüppe
Herne, D-44623
Universitätsklinikum des Saarlandes
Homburg, 66421
Universitätsklinikum Leipzig
Leipzig, 04103
LMU Klinikum der Universität München
München, D-81377
United Kingdom9 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Bristol Royal Infirmary
Bristol, BS2 8HW
Ninewells Hospital Dundee
Dundee, DD1 9SY
Forth Valley Royal Hospital
Larbert, FK5 4WR
The Royal Free Hospital
London, NW3 2QG
Manchester Royal Infirmary
Manchester, M13 9WL
Institute of Cellular Medicine, Newcastle University
Newcastle upon Tyne, NE2 4 HH
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH
Oxford University Hospitals Trust
Oxford, OX3 9DU
Poland5 sites
All-Medicus
Katowice, 40-660
Klinika Gastroenterologii i Hepatologii SP CSK im. prof. K. Gibinskiego SUM
Katowice, 40-752
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, 20-954
Niepubliczny Zakład Opieki Zdrowotnej "SONOMED"
Szczecin, 70-361
Centrum Onkologii - Instytut im. Marii Skłodowskiej - Curie, Klinika Gastroenterologii
Warsaw, 02-781
Italy4 sites
Dip. Medicina Clinica - Università di Bologna
Bologna, 40138
Dip. Medicina Clinica- Università di Bologna
Bologna, 40138
Azienda Ospedaliera di Padova - Gastroenterologia
Padova, 35128
Istituto Clinico Humanitas
Rozzano (MI), 20089
Netherlands4 sites
VUmc Amsterdam
Amsterdam, 1081 HV
AMC Amsterdam
Amsterdam, 1105 AZ
UMC St. Radboud, Nijmegen
Nijmegen, 6525
UMC Utrecht
Utrecht, 3508 GA
Australia3 sites
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Austin Hospital
Heidelberg, Victoria, 3084
The Alfred Hospital
Melbourne, Victoria, 3004
Austria2 sites
Medizinische Universität Innsbruck
Innsbruck, 6020
Medizinische Universität Wien
Vienna, 1090
Canada2 sites
CHUM Hôpital St-Luc
Montreal, Quebec, H2X 3J4
Toronto Western Hospital Liver Centre
Toronto, Ontario, M5T 2S8
Spain2 sites
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
About this study
Official title: A Phase 3, Double-Blind, Placebo-Controlled Trial and Long-Term Safety Extension of Obeticholic Acid in Patients With Primary Biliary Cirrhosis
The main objectives of the study were to assess the effects of Obeticholic Acid (OCA) on serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint and on safety in participants with primary biliary cirrhosis (PBC).
Read the detailed description
The study included 2 phases: a 12-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE) phase up to 5 years. Participants from the 12-month DB phase, including those who received placebo, were eligible to participate in the open-label LTSE phase. The Month 12 visit from the DB phase served as the Day 1 visit of the LTSE phase. After completion of the 12-month DB phase all participants were offered the opportunity to enter an open-label LTSE for up to 5 years beginning at 5 mg OCA.
Data for the LTSE phase is reported by the randomized dose group assigned in the DB phase.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- Obeticholic Acid (OCA), Placebo
- Keywords
- Primary Biliary Cholangitis, Primary Biliary Cirrhosis, PBC, Cirrhosis, Liver
- Medical subject headings
- Liver Cirrhosis, Biliary, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obeticholic Acid (OCA)Drug
Also called 6α-ethyl chenodeoxycholic acid (6-ECDCA), INT-747
OCA was administered orally once daily and provided in tablet form in 2 strengths: 5 mg and 10 mg.
PlaceboDrug
Matching placebo tablets were administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| DB OCA 5-10 mg | Experimental | OCA 5 milligram (mg) for 6 months and then titrating up to 10 mg based on tolerability and response for remaining 6 months of the DB phase. Receives: Drug: Obeticholic Acid (OCA) |
| DB OCA 10 mg | Experimental | OCA 10 mg for 12 months during the DB phase. Receives: Drug: Obeticholic Acid (OCA) |
| DB Placebo | Placebo comparator | Matching placebo for 12 months during the DB phase. Receives: Drug: Placebo |
| LTSE OCA | Experimental | After completion of the 12-month DB phase all participants were offered the opportunity to enter an open-label LTSE for up to 5 years beginning at 5 mg OCA. Initially, participants were allowed to titrate to doses up to 25 mg, however, the maximum dose was then limited to 10 mg. Participants who were previously titrated above 10 mg OCA daily were down-titrated to ≤10 mg OCA daily. Receives: Drug: Obeticholic Acid (OCA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
DB Phase: Composite Endpoint Alkaline Phosphatase (ALP) And Total Bilirubin, 10 mg OCA Versus Placebo
Percentage of participants at Month 12 with ALP < 1.67 x upper limit of normal (ULN) and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline.
Measured: DB Month 12
LTSE Phase: Composite Endpoint ALP And Total Bilirubin
Percentage of participants at Months 24, 36, 48, and 60 with ALP < 1.67x ULN and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline. DB Month 12 is the baseline for the LTSE phase.
Measured: Baseline (DB Month 12), LTSE Months 24, 36, 48, and 60
Secondary outcomes (11)
DB Phase: Composite Endpoint ALP And Total Bilirubin, 10 mg Versus Placebo
Percentage of participants at Month 6 with ALP < 1.67x ULN and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline.
Measured: DB Month 6
DB Phase: Composite Endpoint ALP And Total Bilirubin, 5-10 mg Versus Placebo
Percentage of participants at Month 12 with ALP < 1.67x ULN and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline.
Measured: DB Month 12
DB Phase: Composite Endpoint ALP And Total Bilirubin, 5-10 mg Versus Placebo
Percentage of participants at Month 6 with ALP < 1.67x ULN and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline.
Measured: DB Month 6
DB Phase: ALP Absolute Change From Baseline To Month 12
Blood samples were evaluated for ALP levels. ALP Absolute Change From Baseline (ALP at Month 12 - ALP at Baseline) is presented.
Measured: Baseline, DB Month 12
DB Phase: Total Bilirubin Absolute Change From Baseline To Month 12
Blood samples were evaluated for bilirubin levels. Total bilirubin absolute change from baseline (total bilirubin at Month 12 - total bilirubin at Baseline) is presented.
Measured: Baseline, DB Month 12
DB Phase: Direct Bilirubin Absolute Change From Baseline To Month 12
Blood samples were evaluated for bilirubin levels. Direct bilirubin absolute change from baseline (direct bilirubin at Month 12 - direct bilirubin at Baseline) is presented.
Measured: Baseline, DB Month 12
DB Phase: Alanine Aminotransferase (ALT) Absolute Change From Baseline To Month 12
Blood samples were evaluated for ALT levels. ALT absolute change from baseline (ALT at Month 12 - ALT at Baseline) is presented.
Measured: Baseline, DB Month 12
DB Phase: Aspartate Aminotransferase (AST) Absolute Change From Baseline To Month 12
Blood samples were evaluated for AST levels. AST absolute change from baseline (AST at Month 12 - AST at Baseline) is presented.
Measured: Baseline, DB Month 12
DB Phase: Gamma-glutamyltransferase (GGT) Absolute Change From Baseline To Month 12
Blood samples were evaluated for GGT levels. GGT absolute change from baseline (GGT at Month 12 - GGT at Baseline) is presented.
Measured: Baseline, DB Month 12
LTSE Phase: ALP Levels
Blood samples were evaluated for ALP levels.
Measured: LTSE Day 0 and LTSE Months 12, 24, 36, 48, and 60
LTSE Phase: ALP Change From DB Baseline
Blood samples were evaluated for ALP levels. ALP Change From Baseline (ALP at LTSE Months 12, 24, 36, 48, and 60 - ALP at Baseline) is presented. DB baseline is the mean of all available evaluations prior to DB treatment.
Measured: DB Baseline, LTSE Months 12, 24, 36, 48, and 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2013
- Study completion17 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intercept Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christian Weyer, MD, Study chair, Intercept Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01473524
- Sponsor's protocol ID
- 747-301
- Acronym
- POISE
- Status last verified
- Apr 2021
- First submitted
- 14 Nov 2011
- Last updated
- 6 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
PubMed 19554543Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, Drenth JP, Pockros PJ, Regula J, Beuers U, Trauner M, Jones DE, Floreani A, Hohenester S, Luketic V, Shiffman M, van Erpecum KJ, Vargas V, Vincent C, Hirschfield GM, Shah H, Hansen B, Lindor KD, Marschall HU, Kowdley KV, Hooshmand-Rad R, Marmon T, Sheeron S, Pencek R, MacConell L, Pruzanski M, Shapiro D; POISE Study Group. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med. 2016 Aug 18;375(7):631-43. doi: 10.1056/NEJMoa1509840.
PubMed 27532829Trauner M, Nevens F, Shiffman ML, Drenth JPH, Bowlus CL, Vargas V, Andreone P, Hirschfield GM, Pencek R, Malecha ES, MacConell L, Shapiro D. Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study. Lancet Gastroenterol Hepatol. 2019 Jun;4(6):445-453. doi: 10.1016/S2468-1253(19)30094-9. Epub 2019 Mar 26.
PubMed 30922873Bowlus CL, Nevens F, Kowdley KV, Bonder A, Capozza T, Li J, Nair R, Trauner M, Jones DE. Long-Term Safety and Efficacy of Obeticholic Acid in Patients With Primary Biliary Cholangitis: Final Results of the POISE Long-Term Safety Extension. Aliment Pharmacol Ther. 2026 Jul 14. doi: 10.1111/apt.70832. Online ahead of print.
PubMed 42449190Harms MH, Hirschfield GM, Floreani A, Mayo MJ, Pares A, Liberman A, Malecha ES, Pencek R, MacConell L, Hansen BE. Obeticholic acid is associated with improvements in AST-to-platelet ratio index and GLOBE score in patients with primary biliary cholangitis. JHEP Rep. 2020 Sep 29;3(1):100191. doi: 10.1016/j.jhepr.2020.100191. eCollection 2021 Feb.
PubMed 33319187Bowlus CL, Pockros PJ, Kremer AE, Pares A, Forman LM, Drenth JPH, Ryder SD, Terracciano L, Jin Y, Liberman A, Pencek R, Iloeje U, MacConell L, Bedossa P. Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2020 May;18(5):1170-1178.e6. doi: 10.1016/j.cgh.2019.09.050. Epub 2019 Oct 10.
PubMed 31606455Mousa HS, Lleo A, Invernizzi P, Bowlus CL, Gershwin ME. Advances in pharmacotherapy for primary biliary cirrhosis. Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.
PubMed 25543678
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Placebo-Controlled Trial and Long-Term Safety Extension of Obeticholic Acid in Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT01473524
- Acronym / sponsor ID
- POISE / 747-301
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- Primary Biliary Cholangitis, Primary Biliary Cirrhosis, PBC, Cirrhosis, Liver
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- Intercept PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- 17 Dec 2018 (actual)
- First posted
- 17 Nov 2011 (estimated)
- Results
- Posted 13 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objectives of the study were to assess the effects of Obeticholic Acid (OCA) on serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint and on safety in participants with primary biliary cirrhosis (PBC).
Detailed description
The study included 2 phases: a 12-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE) phase up to 5 years. Participants from the 12-month DB phase, including those who received placebo, were eligible to participate in the open-label LTSE phase. The Month 12 visit from the DB phase served as the Day 1 visit of the LTSE phase. After completion of the 12-month DB phase all participants were offered the opportunity to enter an open-label LTSE for up to 5 years beginning at 5 mg OCA.
Data for the LTSE phase is reported by the randomized dose group assigned in the DB phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| DB OCA 5-10 mg | Experimental | Drug: Obeticholic Acid (OCA)OCA 5 milligram (mg) for 6 months and then titrating up to 10 mg based on tolerability and response for remaining 6 months of the DB phase. |
| DB OCA 10 mg | Experimental | Drug: Obeticholic Acid (OCA)OCA 10 mg for 12 months during the DB phase. |
| DB Placebo | Placebo comparator | Drug: PlaceboMatching placebo for 12 months during the DB phase. |
| LTSE OCA | Experimental | Drug: Obeticholic Acid (OCA)After completion of the 12-month DB phase all participants were offered the opportunity to enter an open-label LTSE for up to 5 years beginning at 5 mg OCA. Initially, participants were allowed to titrate to doses up to 25 mg, however, the maximum dose was then limited to 10 mg. Participants who were previously titrated above 10 mg OCA daily were down-titrated to ≤10 mg OCA daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:
- At least 1 of the following qualifying biochemistry values:
- Age ≥ 18 years
- Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0.
- Contraception: Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and for 30 days after the end of treatment (EOT) visit. Effective methods of contraception are considered to be:
Key exclusion criteria (29 listed)
- History or presence of other concomitant liver diseases including:
- Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
- Participants with severe pruritus or those requiring systemic treatment for pruritus (for example, with bile acid sequestrants [BAS] or rifampicin) within 2 months of Day 0 will be excluded
- Administration of the following medications is prohibited as specified below:
- Participants who have previously participated in a clinical trial of OCA will not be allowed to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Obeticholic Acid (OCA)Also: 6α-ethyl chenodeoxycholic acid (6-ECDCA), INT-747OCA was administered orally once daily and provided in tablet form in 2 strengths: 5 mg and 10 mg. | Drug | DB OCA 10 mg, DB OCA 5-10 mg, LTSE OCA |
| PlaceboMatching placebo tablets were administered orally once daily. | Drug | DB Placebo |
Primary outcome
DB Phase: Composite Endpoint Alkaline Phosphatase (ALP) And Total Bilirubin, 10 mg OCA Versus Placebo
Time frame: DB Month 12
Percentage of participants at Month 12 with ALP < 1.67 x upper limit of normal (ULN) and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline.
LTSE Phase: Composite Endpoint ALP And Total Bilirubin
Time frame: Baseline (DB Month 12), LTSE Months 24, 36, 48, and 60
Percentage of participants at Months 24, 36, 48, and 60 with ALP < 1.67x ULN and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline. DB Month 12 is the baseline for the LTSE phase.
11 secondary outcomes
DB Phase: Composite Endpoint ALP And Total Bilirubin, 10 mg Versus Placebo
Time frame: DB Month 6
DB Phase: Composite Endpoint ALP And Total Bilirubin, 5-10 mg Versus Placebo
Time frame: DB Month 12
DB Phase: Composite Endpoint ALP And Total Bilirubin, 5-10 mg Versus Placebo
Time frame: DB Month 6
DB Phase: ALP Absolute Change From Baseline To Month 12
Time frame: Baseline, DB Month 12
DB Phase: Total Bilirubin Absolute Change From Baseline To Month 12
Time frame: Baseline, DB Month 12
DB Phase: Direct Bilirubin Absolute Change From Baseline To Month 12
Time frame: Baseline, DB Month 12
DB Phase: Alanine Aminotransferase (ALT) Absolute Change From Baseline To Month 12
Time frame: Baseline, DB Month 12
DB Phase: Aspartate Aminotransferase (AST) Absolute Change From Baseline To Month 12
Time frame: Baseline, DB Month 12
DB Phase: Gamma-glutamyltransferase (GGT) Absolute Change From Baseline To Month 12
Time frame: Baseline, DB Month 12
LTSE Phase: ALP Levels
Time frame: LTSE Day 0 and LTSE Months 12, 24, 36, 48, and 60
LTSE Phase: ALP Change From DB Baseline
Time frame: DB Baseline, LTSE Months 12, 24, 36, 48, and 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19554543Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
- Results publication: PubMed 27532829Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, Drenth JP, Pockros PJ, Regula J, Beuers U, Trauner M, Jones DE, Floreani A, Hohenester S, Luketic V, Shiffman M, van Erpecum KJ, Vargas V, Vincent C, Hirschfield GM, Shah H, Hansen B, Lindor KD, Marschall HU, Kowdley KV, Hooshmand-Rad R, Marmon T, Sheeron S, Pencek R, MacConell L, Pruzanski M, Shapiro D; POISE Study Group. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med. 2016 Aug 18;375(7):631-43. doi: 10.1056/NEJMoa1509840.
- Results publication: PubMed 30922873Trauner M, Nevens F, Shiffman ML, Drenth JPH, Bowlus CL, Vargas V, Andreone P, Hirschfield GM, Pencek R, Malecha ES, MacConell L, Shapiro D. Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study. Lancet Gastroenterol Hepatol. 2019 Jun;4(6):445-453. doi: 10.1016/S2468-1253(19)30094-9. Epub 2019 Mar 26.
- Derived from this study: PubMed 42449190Bowlus CL, Nevens F, Kowdley KV, Bonder A, Capozza T, Li J, Nair R, Trauner M, Jones DE. Long-Term Safety and Efficacy of Obeticholic Acid in Patients With Primary Biliary Cholangitis: Final Results of the POISE Long-Term Safety Extension. Aliment Pharmacol Ther. 2026 Jul 14. doi: 10.1111/apt.70832. Online ahead of print.
- Derived from this study: PubMed 33319187Harms MH, Hirschfield GM, Floreani A, Mayo MJ, Pares A, Liberman A, Malecha ES, Pencek R, MacConell L, Hansen BE. Obeticholic acid is associated with improvements in AST-to-platelet ratio index and GLOBE score in patients with primary biliary cholangitis. JHEP Rep. 2020 Sep 29;3(1):100191. doi: 10.1016/j.jhepr.2020.100191. eCollection 2021 Feb.
- Derived from this study: PubMed 31606455Bowlus CL, Pockros PJ, Kremer AE, Pares A, Forman LM, Drenth JPH, Ryder SD, Terracciano L, Jin Y, Liberman A, Pencek R, Iloeje U, MacConell L, Bedossa P. Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2020 May;18(5):1170-1178.e6. doi: 10.1016/j.cgh.2019.09.050. Epub 2019 Oct 10.
- Derived from this study: PubMed 25543678Mousa HS, Lleo A, Invernizzi P, Bowlus CL, Gershwin ME. Advances in pharmacotherapy for primary biliary cirrhosis. Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.
Related trials for Primary Biliary Cirrhosis
Active, not recruitingPhase 3
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cirrhosis
RecruitingPhase 3
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
Primary Biliary Cholangitis
RecruitingPhase 3
FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy
Primary Biliary Cholangitis (PBC)
RecruitingPhase 3
Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid
Primary Biliary Cirrhosis
RecruitingPhase 2/3
Fenofibrate in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Weyer, MD study chair
Intercept Pharmaceuticals, Inc.
59 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Obeticholic Acid (OCA) in people with Primary Biliary Cirrhosis, run by Intercept Pharmaceuticals at 59 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in United States, Germany, United Kingdom, Poland, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DB Phase: Composite Endpoint Alkaline Phosphatase (ALP) And Total Bilirubin, 10 mg OCA Versus Placebo (time frame: DB Month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01473524, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.