Primary Sclerosing Cholangitis (PSC)Phase 2AESOPNCT02177136
Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC)
A Phase 2 study testing Obeticholic Acid (OCA) in people with Primary Sclerosing Cholangitis (PSC), run by Intercept Pharmaceuticals at 36 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Sclerosing Cholangitis (PSC)
- What is being tested?
- Obeticholic Acid (OCA)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 36 sitesin 2 countries
- Study dates
- 9 Feb 2015to 22 Mar 2018
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have had a diagnosis of PSC (based on cholangiography at any point in time).
- Alkaline phosphatase at Screening ≥2x ULN.
- Total bilirubin at Screening <2.5x ULN.
- For participants with concomitant inflammatory bowel disease (IBD):
- Colonoscopy (if participant has a colon) or other appropriate endoscopic procedure within 12 months of Day 0 confirming no dysplasia or colorectal cancer
- Participants with Crohn's Disease (CD) must have been in remission as defined by a Crohn's Disease Activity Index (CDAI) <150
Show all 10Show fewer
- Participants with ulcerative colitis (UC) must either have been in remission or have had mild disease. Remission was defined as a partial Mayo score of ≤2 with no individual sub-score exceeding 1. Mild disease was defined as a partial Mayo score ≤3 with no individual sub-score exceeding 1 point.
- For participants being administered UDCA as part of their standard of care, the dose must have been stable for ≥3 months prior to, and including, Day 0 and must not have exceeded 20 mg/kilograms/day during this time.
- Participants being administered biologic treatments (for example, anti-tumor necrosis factor or anti-integrin monoclonal antibodies), immunosuppressants, systemic corticosteroids, or statins, must have been on a stable dose for ≥3 months prior to, and including, Day 0 and should plan to remain on a stable dose throughout the trial.
- Contraception: female participants of childbearing potential must have used ≥1 effective method (≤1% failure rate) of contraception during the trial and until 4 weeks following the last dose of IP (including LTSE doses).
Who cannot join
- Evidence of a secondary cause of sclerosing cholangitis at Screening.
- Immunoglobulin G4 (IgG4) >4x ULN at Screening or evidence of IgG4 sclerosing cholangitis.
- Small duct cholangitis in the absence of large duct disease.
- Presence of clinical complications of chronic liver disease or clinically significant hepatic decompensation, including:
- Current Child Pugh classification B or C
- History of, or current diagnosis or suspicion of, cholangiocarcinoma or other hepatobiliary malignancy, or biliary tract dysplasia.
Show all 33Show fewer
- History of liver transplantation, or current model of end stage liver disease score ≥12
- History of, or current, cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis hepatocellular carcinoma or hepatic encephalopathy (as assessed by the Investigator)
- Current known 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).
- History of, or current, hepatorenal syndrome (type I or II) or Screening serum creatinine >2 mg/deciliter (178 micromoles/liter [L]).
- Platelet count <50 x 10^9/L.
- Current clinical evidence of dominant strictures that were considered clinically relevant in the opinion of the Investigator or current biliary stent at Screening.
- Current cholecystitis or evidence of current biliary obstruction due to gallstones. Asymptomatic gallstones that were not considered a safety risk in the opinion of the Investigator might have been acceptable, subject to discussion and agreement with the Medical Monitor.
- Colonic dysplasia within ≤5 years prior to Day 0.
- History of small bowel resection.
- History of other chronic liver diseases, including, but not limited to, primary biliary cholangitis (PBC), alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, hepatitis B virus (unless seroconverted and no positive Hepatitis B Virus deoxyribonucleic acid), hepatitis C virus and overlap syndrome.
- Known Gilbert's syndrome or history of elevations in unconjugated (indirect) bilirubin >ULN or unconjugated (indirect) bilirubin >ULN at Screening.
- Known history of human immunodeficiency virus infection.
- Currently experiencing, or experienced within ≤3 months of Screening, pruritus requiring systemic or enteral treatment.
- Known or suspected acute cholangitis in the 3 months prior to, and including, Day 0 including cholangitis treated with antibiotics.
- Administration of antibiotics is prohibited ≤1 month of Day 0 (unless participant was on a stable prophylaxis dose for at least 3 months prior to Day 0).
- Administration of the following medications was prohibited ≤6 months of Day 0 and throughout the trial: fenofibrate or other fibrates and potentially hepatotoxic medications (including alpha-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin).
- IBD flare during Screening (up to and including Day 0), where "flare" was defined as follows:
- UC flare: partial Mayo Score ≥5, and
- CD flare: CDAI ≥250
- Evidence of deleterious effects of alcohol abuse (as assessed by the Investigator) or excessive alcohol consumption (>4 units/day for males, >2 units/day for females).
- Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated) within 3 months of Day 0.
- If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
- Other concomitant disease, malignancy, or condition likely to significantly decrease life expectancy to less than the duration of the trial (for example, moderate to severe congestive heart failure).
- 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 were 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 was uncertain.
Trial locations and contacts
36 sites in 2 countries.
36 sites in 2 countries
United States33 sites
Piedmont Atlanta Georgia Transplant Institute
Atlanta, Georgia, 30309
University of Colorado, Denver
Aurora, Colorado, 80045
Mercy Medical Center
Baltimore, Maryland, 21202
Johns Hopkins University
Baltimore, Maryland, 21287
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203
Baylor University Medical Center
Dallas, Texas, 75246
Henry Ford Health System
Detroit, Michigan, 48202
CHI St. Luke's Health Baylor College of Medicine Medical Center
Houston, Texas, 77030
Liver Associates of Texas, P.A.
Houston, Texas, 77030
Indiana University Health University Hospital
Indianapolis, Indiana, 46202
Southern Therapy and Advanced Research
Jackson, Mississippi, 39216
University of Louisville
Louisville, Kentucky, 40202
Gastrointestinal Specialists of Georgia
Marietta, Georgia, 30060
University of Miami Hospital
Miami, Florida, 33136
Tulane Medical Center
New Orleans, Louisiana, 70112
Weill Cornell Medical College
New York, New York, 10021
Mount Sinai Medical Center
New York, New York, 10029
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
St. Joseph's Hospital & Medical Center
Phoenix, Arizona, 85013
Mayo Clinic
Phoenix, Arizona, 85054
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
McGuire DVAMC
Richmond, Virginia, 23249
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester Medical Center
Rochester, New York, 14642
University of California Davis Medical Center
Sacramento, California, 95817
Swedish Organ Transplant and Liver Center
Seattle, Washington, 98104
Texas Digestive Disease Consultants
Southlake, Texas, 76092
St. Louis University Gastroenterology & Hepatology
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Italy3 sites
Dipartimento di Universitario di Scienze Mediche e Chirurgiche
Bologna, 40138
Azienda Socio Sanitaria Territoriale di Monza
Monza, 20900
Azienda Ospedaliera Universita di Padova - Struttura Operativa Complessa Gastroenterologia
Padova, 35128
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Clinical Trial Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Primary Sclerosing Cholangitis
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.
Read the detailed description
This was a phase 2, randomized, double-blind, placebo-controlled, dose-finding evaluation of the efficacy and safety of OCA in participants with PSC. Approximately 75 participants who provided written informed consent and met all of the inclusion and none of the exclusion criteria were randomized to 1 of 3 treatment groups as follows: 1.5 milligrams (mg) titrating to 3 mg OCA, 5 mg titrating to 10 mg OCA, or placebo, in a 1:1:1 ratio. Participants self-administered investigational product (IP) orally, once daily for 2 consecutive 12-week periods.
For the first 12 weeks, the participant's dose was 1.5 mg OCA, 5 mg OCA, or placebo. After 12 weeks, the participant's dose was titrated as follows, providing there were no limiting safety or tolerability concerns in the opinion of the Investigator, while maintaining the trial blind: the 1.5 mg OCA treatment group titrated to 3 mg, the 5 mg OCA treatment group titrated to 10 mg OCA, and the placebo group remained on placebo. Double-blind treatment continued for a further 12 weeks at that dose.
Any participant whose dose was not titrated, due to safety or tolerability concerns, remained on their starting treatment (1.5 mg OCA, 5 mg OCA, or placebo) for the remainder of the DB phase to Week 24.
Randomization was stratified by the presence or absence of concomitant ursodeoxycholic acid (UDCA) use and total bilirubin level (≤1.5x upper limit of normal [ULN] or >1.5x ULN but <2.5x ULN).
Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the open-label LTSE phase (planned as a further 24 months).
- Conditions
- Primary Sclerosing Cholangitis (PSC)
- Being tested
- Obeticholic Acid (OCA), Placebo
- Keywords
- PSC
- Medical subject headings
- Cholangitis, Sclerosing
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 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 1.5 mg OCA titrating to 3 mg OCA | Experimental | 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. Receives: Drug: Obeticholic Acid (OCA) |
| 5 mg OCA titrating to 10 mg OCA | Experimental | 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. Receives: Drug: Obeticholic Acid (OCA) |
| Placebo | Experimental | Participants randomized to placebo took placebo for 24 weeks during the DB phase. Receives: Drug: Placebo |
| LTSE OCA Total | Experimental | 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. Receives: Drug: Obeticholic Acid (OCA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
DB Phase: Change From Baseline In Serum Alkaline Phosphatase (ALP)
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.
Measured: Baseline, Week 24
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs)
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.
Measured: LTSE Baseline (DB Week 24) to Month 26
Secondary outcomes (23)
DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT)
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.
Measured: Baseline, Week 24
DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST)
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.
Measured: Baseline, Week 24
DB Phase: Change From Baseline In Serum Total Bilirubin
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.
Measured: Baseline, Week 24
DB Phase: Change From Baseline In Serum Direct Bilirubin
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.
Measured: Baseline, Week 24
DB Phase: Change From Baseline In Serum Gamma-glutamyl Transferase (GGT)
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.
Measured: Baseline, Week 24
DB Phase: Change From Baseline In Plasma Fibroblast Growth Factor-19 (FGF-19)
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).
Measured: Baseline, Week 24
DB Phase: Change From Baseline In Plasma 7α-Hydroxy-4-cholesten-3-one (C4)
To assess FXR activity, the change in plasma C4 from Baseline at Week 24 is reported. Results are reported in nanograms (ng)/mL.
Measured: Baseline, Week 24
LTSE Phase: Change From Baseline In Serum ALP At 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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum ALT At 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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum AST At 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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum Total Bilirubin At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum Direct Bilirubin At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum GGT At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Albumin At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In INR At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Transient Elastography (TE) At Month 12
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).
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Enhanced Liver Fibrosis (ELF) At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Plasma FGF-19 At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Plasma C4 At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Participants Experiencing Ulcerative Colitis Remission At Month 12
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.
Measured: Month 12
LTSE Phase: Participants Experiencing Crohn's Disease Remission At Month 12
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.
Measured: Month 12
LTSE Phase: Change From Baseline In Total Bile Acids At Month 12
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.
Measured: Month 12
LTSE Phase: Change From Baseline In Pruritus Visual Analogue Scale (VAS) At Month 12
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.
Measured: LTSE Baseline (DB Week 24), Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2014 (estimated)
- Study start9 Feb 2015
- Primary completion7 Mar 2017
- Study completion22 Mar 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 (1)Papers the sponsor has linked to this study.
- Other trials for Primary Sclerosing Cholangitis (PSC)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intercept Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- George Harb, MD, Study chair, Intercept Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02177136
- Sponsor's protocol ID
- 747-207
- Other IDs
- 2014-002205-38, 2014
- Acronym
- AESOP
- Status last verified
- Jun 2021
- First submitted
- 26 Jun 2014
- Last updated
- 8 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kowdley KV, Vuppalanchi R, Levy C, Floreani A, Andreone P, LaRusso NF, Shrestha R, Trotter J, Goldberg D, Rushbrook S, Hirschfield GM, Schiano T, Jin Y, Pencek R, MacConell L, Shapiro D, Bowlus CL; AESOP Study Investigators. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis. J Hepatol. 2020 Jul;73(1):94-101. doi: 10.1016/j.jhep.2020.02.033. Epub 2020 Mar 10.
PubMed 32165251
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Clinical Trial Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Primary Sclerosing Cholangitis
- ClinicalTrials.gov ID
- NCT02177136
- Acronym / sponsor ID
- AESOP / 747-207
- Conditions
- Primary Sclerosing Cholangitis (PSC)
- Keywords
- PSC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Intercept PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Feb 2015 (actual)
- Primary completion
- 7 Mar 2017 (actual)
- Study completion
- 22 Mar 2018 (actual)
- First posted
- 27 Jun 2014 (estimated)
- Results
- Posted 30 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This was a phase 2, randomized, double-blind, placebo-controlled, dose-finding evaluation of the efficacy and safety of OCA in participants with PSC. Approximately 75 participants who provided written informed consent and met all of the inclusion and none of the exclusion criteria were randomized to 1 of 3 treatment groups as follows: 1.5 milligrams (mg) titrating to 3 mg OCA, 5 mg titrating to 10 mg OCA, or placebo, in a 1:1:1 ratio. Participants self-administered investigational product (IP) orally, once daily for 2 consecutive 12-week periods.
For the first 12 weeks, the participant's dose was 1.5 mg OCA, 5 mg OCA, or placebo. After 12 weeks, the participant's dose was titrated as follows, providing there were no limiting safety or tolerability concerns in the opinion of the Investigator, while maintaining the trial blind: the 1.5 mg OCA treatment group titrated to 3 mg, the 5 mg OCA treatment group titrated to 10 mg OCA, and the placebo group remained on placebo. Double-blind treatment continued for a further 12 weeks at that dose.
Any participant whose dose was not titrated, due to safety or tolerability concerns, remained on their starting treatment (1.5 mg OCA, 5 mg OCA, or placebo) for the remainder of the DB phase to Week 24.
Randomization was stratified by the presence or absence of concomitant ursodeoxycholic acid (UDCA) use and total bilirubin level (≤1.5x upper limit of normal [ULN] or >1.5x ULN but <2.5x ULN).
Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the open-label LTSE phase (planned as a further 24 months).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1.5 mg OCA titrating to 3 mg OCA | Experimental | Drug: Obeticholic Acid (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 | Experimental | Drug: Obeticholic Acid (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 | Experimental | Drug: PlaceboParticipants randomized to placebo took placebo for 24 weeks during the DB phase. |
| LTSE OCA Total | Experimental | Drug: Obeticholic Acid (OCA)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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Must have had a diagnosis of PSC (based on cholangiography at any point in time).
- Alkaline phosphatase at Screening ≥2x ULN.
- Total bilirubin at Screening <2.5x ULN.
- For participants with concomitant inflammatory bowel disease (IBD):
- For participants being administered UDCA as part of their standard of care, the dose must have been stable for ≥3 months prior to, and including, Day 0 and must not have exceeded 20 mg/kilograms/day during this time.
Key exclusion criteria (33 listed)
- Evidence of a secondary cause of sclerosing cholangitis at Screening.
- Immunoglobulin G4 (IgG4) >4x ULN at Screening or evidence of IgG4 sclerosing cholangitis.
- Small duct cholangitis in the absence of large duct disease.
- Presence of clinical complications of chronic liver disease or clinically significant hepatic decompensation, including:
- Current clinical evidence of dominant strictures that were considered clinically relevant in the opinion of the Investigator or current biliary stent at Screening.
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: 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747 | Drug | 1.5 mg OCA titrating to 3 mg OCA, 5 mg OCA titrating to 10 mg OCA, LTSE OCA Total |
| Placebo | Drug | Placebo |
Primary outcome
DB Phase: Change From Baseline In Serum Alkaline Phosphatase (ALP)
Time frame: 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.
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs)
Time frame: 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. 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.
23 secondary outcomes
DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT)
Time frame: Baseline, Week 24
DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST)
Time frame: Baseline, Week 24
DB Phase: Change From Baseline In Serum Total Bilirubin
Time frame: Baseline, Week 24
DB Phase: Change From Baseline In Serum Direct Bilirubin
Time frame: Baseline, Week 24
DB Phase: Change From Baseline In Serum Gamma-glutamyl Transferase (GGT)
Time frame: Baseline, Week 24
DB Phase: Change From Baseline In Plasma Fibroblast Growth Factor-19 (FGF-19)
Time frame: Baseline, Week 24
DB Phase: Change From Baseline In Plasma 7α-Hydroxy-4-cholesten-3-one (C4)
Time frame: Baseline, Week 24
LTSE Phase: Change From Baseline In Serum ALP At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum ALT At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum AST At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum Total Bilirubin At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum Direct Bilirubin At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Serum GGT At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Albumin At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In INR At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Transient Elastography (TE) At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Enhanced Liver Fibrosis (ELF) At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Plasma FGF-19 At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Change From Baseline In Plasma C4 At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
LTSE Phase: Participants Experiencing Ulcerative Colitis Remission At Month 12
Time frame: Month 12
LTSE Phase: Participants Experiencing Crohn's Disease Remission At Month 12
Time frame: Month 12
LTSE Phase: Change From Baseline In Total Bile Acids At Month 12
Time frame: Month 12
LTSE Phase: Change From Baseline In Pruritus Visual Analogue Scale (VAS) At Month 12
Time frame: LTSE Baseline (DB Week 24), Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32165251Kowdley KV, Vuppalanchi R, Levy C, Floreani A, Andreone P, LaRusso NF, Shrestha R, Trotter J, Goldberg D, Rushbrook S, Hirschfield GM, Schiano T, Jin Y, Pencek R, MacConell L, Shapiro D, Bowlus CL; AESOP Study Investigators. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis. J Hepatol. 2020 Jul;73(1):94-101. doi: 10.1016/j.jhep.2020.02.033. Epub 2020 Mar 10.
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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.
George Harb, MD study chair
Intercept Pharmaceuticals, Inc.
36 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Obeticholic Acid (OCA) in people with Primary Sclerosing Cholangitis (PSC), run by Intercept Pharmaceuticals at 36 sites in 2 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 10 inclusion and 33 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 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Italy. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 May 2018). 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: Change From Baseline In Serum Alkaline Phosphatase (ALP) (time frame: Baseline, Week 24). 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 NCT02177136, which also lists 1 linked publication.
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 8 Jul 2021.