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

NCT02177136 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 747-2072014-002205-38
• Study Type: interventional
• Target: 77
• Locations: 2 countries
• Sites: 36

Brief 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. 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.

Conditions

Primary Sclerosing Cholangitis (PSC)

Keywords

PSC

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  LTSE Baseline (DB Week 24) to Month 26

Secondary Outcomes (23)

• DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT)

  Baseline, Week 24

• DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST)

  Baseline, Week 24

• DB Phase: Change From Baseline In Serum Total Bilirubin

  Baseline, Week 24

• DB Phase: Change From Baseline In Serum Direct Bilirubin

  Baseline, Week 24

• DB Phase: Change From Baseline In Serum Gamma-glutamyl Transferase (GGT)

  Baseline, Week 24

Study Arms (4)

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.

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.

Drug: Obeticholic Acid (OCA)

Placebo

EXPERIMENTAL

Participants randomized to placebo took placebo for 24 weeks during the DB phase.

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.

Drug: Obeticholic Acid (OCA)

Interventions

Obeticholic Acid (OCA) DRUG

Also known as: 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747

1.5 mg OCA titrating to 3 mg OCA; 5 mg OCA titrating to 10 mg OCA; LTSE OCA Total

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (36)

St. Joseph's Hospital & Medical Center

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Colorado, Denver

Aurora, Colorado, 80045, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Piedmont Atlanta Georgia Transplant Institute

Atlanta, Georgia, 30309, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Southern Therapy and Advanced Research

Jackson, Mississippi, 39216, United States

Location

St. Louis University Gastroenterology & Hepatology

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

CHI St. Luke's Health Baylor College of Medicine Medical Center

Houston, Texas, 77030, United States

Location

Liver Associates of Texas, P.A.

Houston, Texas, 77030, United States

Location

Texas Digestive Disease Consultants

Southlake, Texas, 76092, United States

Location

McGuire DVAMC

Richmond, Virginia, 23249, United States

Location

Swedish Organ Transplant and Liver Center

Seattle, Washington, 98104, United States

Location

Dipartimento di Universitario di Scienze Mediche e Chirurgiche

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale di Monza

Monza, 20900, Italy

Location

Azienda Ospedaliera Universita di Padova - Struttura Operativa Complessa Gastroenterologia

Padua, 35128, Italy

Location

Related Publications (1)

• 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.

  PMID: 32165251 RESULT

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

obeticholic acid

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Limitations and Caveats

Due to administrative reasons, the study was terminated by the Sponsor prior to most participants completing LTSE Month 24.

Results Point of Contact

• Title: Medical Information
• Organization: Intercept Pharmaceuticals, Inc.

medinfo@interceptpharma.com

844-782-4278

Study Officials

• George Harb, MD

  Intercept Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the open-label LTSE phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2014
• First Posted: June 27, 2014
• Study Start: February 9, 2015
• Primary Completion: March 7, 2017
• Study Completion: March 22, 2018
• Last Updated: July 8, 2021
• Results First Posted: May 30, 2018

Record last verified: 2021-06

Locations

IT (3); US (33)