NCT01265498

Brief Summary

Administration of the farnesoid X receptor (FXR) ligand obeticholic acid (OCA) for 72 weeks to subjects with biopsy evidence of nonalcoholic steatohepatitis (NASH) will result in improvement in their liver disease as measured by changes in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
283

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Mar 2011

Typical duration for phase_2

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 21, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 23, 2010

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2011

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2014

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
12 months until next milestone

Results Posted

Study results publicly available

August 21, 2015

Completed
Last Updated

April 6, 2018

Status Verified

July 1, 2015

Enrollment Period

2.8 years

First QC Date

December 21, 2010

Results QC Date

June 26, 2015

Last Update Submit

March 12, 2018

Conditions

Nonalcoholic Fatty Liver Disease (NAFLD)Nonalcoholic Steatohepatitis (NASH)

Keywords

Farnesoid X ReceptorFXRNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisNAFLDNASHobeticholic acid

Outcome Measures

Primary Outcomes (1)

  • Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

    Centrally scored histological improvement in nonalcoholic fatty liver disease (NAFLD) from baseline to the end of 72 weeks of treatment, where improvement is defined as: 1. No worsening in fibrosis; and 2. A decrease in NAFLD Activity Score (NAS) of at least 2 points

    baseline to 72 weeks

Secondary Outcomes (47)

  • Resolution of NASH Diagnosis

    baseline to 72 weeks

  • Fibrosis: Patient With Improvement

    baseline to 72 weeks

  • Fibrosis: Change in Score

    baseline to 72 weeks

  • Total NAFLD Activity Score: Change in Score

    baseline to 72 weeks

  • Hepatocellular Ballooning: Patients With Improvement

    baseline to 72 weeks

  • +42 more secondary outcomes

Study Arms (2)

Obeticholic acid

ACTIVE COMPARATOR

obeticholic acid

Drug: obeticholic acid

Placebo

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

obeticholic acidDRUG

25 mg daily for 72 weeks

Also known as: farnesoid X receptor (FXR) ligand obeticholic acid (OCA)
Obeticholic acid
placeboDRUG

placebo capsule, 25 mg daily for 72 weeks

Also known as: Placebo for obeticholic acid
Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age or older as of the initial screening interview and provision of consent
  • Histologic evidence of definite or probable nonalcoholic steatohepatitis (NASH) based upon a liver biopsy obtained no more than 90 days prior to randomization and a nonalcoholic fatty liver disease activity score (NAS) of 4 or greater with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).

You may not qualify if:

  • Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males, on average)
  • Inability to reliably quantify alcohol consumption based upon local study physician judgment
  • Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the year prior to randomization
  • Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass)
  • Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher within 60 days prior to enrollment
  • Presence of cirrhosis on liver biopsy
  • A platelet count below 100,000/mm3
  • Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
  • Serum albumin less than 3.2 grams/deciliter (g/dL)
  • International Normalized Ratio(INR)greater than 1.3
  • Direct bilirubin greater than 1.3 milligrams per deciliter (mg/dL)
  • History of esophageal varices, ascites or hepatic encephalopathy
  • Evidence of other forms of chronic liver disease:
  • Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
  • Hepatitis C as defined by presence of hepatitis C virus (HCV) ribonucleic acid (RNA) or positive hepatitis C antibody (anti-HCV)
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

University of California, San Diego

San Diego, California, 92103, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Related Publications (7)

  • Shen W, Middleton MS, Cunha GM, Delgado TI, Wolfson T, Gamst A, Fowler KJ, Alazraki A, Trout AT, Ohliger MA, Shah SN, Bashir MR, Kleiner DE, Loomba R, Neuschwander-Tetri BA, Sanyal AJ, Zhou J, Sirlin CB, Lavine JE. Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis. J Hepatol. 2023 Feb;78(2):238-246. doi: 10.1016/j.jhep.2022.10.027. Epub 2022 Nov 8.

    PMID: 36368598DERIVED

  • Vilar-Gomez E, Gawrieh S, Liang T, McIntyre AD, Hegele RA, Chalasani N. Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD. J Clin Lipidol. 2021 Mar-Apr;15(2):275-291. doi: 10.1016/j.jacl.2020.12.010. Epub 2020 Dec 27.

    PMID: 33454241DERIVED

  • Loomba R, Neuschwander-Tetri BA, Sanyal A, Chalasani N, Diehl AM, Terrault N, Kowdley K, Dasarathy S, Kleiner D, Behling C, Lavine J, Van Natta M, Middleton M, Tonascia J, Sirlin C; NASH Clinical Research Network. Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH. Hepatology. 2020 Oct;72(4):1219-1229. doi: 10.1002/hep.31121. Epub 2020 Oct 9.

    PMID: 31965579DERIVED

  • Siddiqui MS, Van Natta ML, Connelly MA, Vuppalanchi R, Neuschwander-Tetri BA, Tonascia J, Guy C, Loomba R, Dasarathy S, Wattacheril J, Chalasani N, Sanyal AJ; NASH CRN. Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis. J Hepatol. 2020 Jan;72(1):25-33. doi: 10.1016/j.jhep.2019.10.006. Epub 2019 Oct 18.

    PMID: 31634532DERIVED

  • Chalasani N, Abdelmalek MF, Loomba R, Kowdley KV, McCullough AJ, Dasarathy S, Neuschwander-Tetri BA, Terrault N, Ferguson B, Shringarpure R, Shapiro D, Sanyal AJ. Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis. Liver Int. 2019 May;39(5):924-932. doi: 10.1111/liv.13974. Epub 2019 Feb 21.

    PMID: 30253043DERIVED

  • Hameed B, Terrault NA, Gill RM, Loomba R, Chalasani N, Hoofnagle JH, Van Natta ML; NASH CRN. Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2018 Mar;47(5):645-656. doi: 10.1111/apt.14492. Epub 2018 Jan 14.

    PMID: 29333665DERIVED

  • Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015 Mar 14;385(9972):956-65. doi: 10.1016/S0140-6736(14)61933-4. Epub 2014 Nov 7.

    PMID: 25468160DERIVED

Related Links

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

obeticholic acidfarnesoid X-activated receptor

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System Diseases

Results Point of Contact

Title
Mark Van Natta
Organization
Johns Hopkins Data Coordinating Centers
mvannat1@jhu.edu
410-614-1362

Study Officials

  • Edward Doo, MD

    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 21, 2010

First Posted

December 23, 2010

Study Start

March 1, 2011

Primary Completion

January 1, 2014

Study Completion

September 1, 2014

Last Updated

April 6, 2018

Results First Posted

August 21, 2015

Record last verified: 2015-07

Locations

US(9)