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



Status:Completed
Conditions:Gastrointestinal, Gastrointestinal
Therapuetic Areas:Gastroenterology
Healthy:No
Age Range:18 - 75
Updated:6/1/2018
Start Date:February 9, 2015
End Date:March 22, 2018

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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 is a phase 2, double-blind, placebo controlled trial in patients with primary sclerosing
cholangitis to evaluate the effect of obeticholic acid on liver biochemistry, in particular,
serum alkaline phosphatase; and, safety.

This is a Phase 2, randomized, double-blind, placebo-controlled, dose-finding evaluation of
the efficacy and safety of OCA in subjects with PSC. Approximately 75 subjects who provide
written informed consent and meet all of the inclusion and none of the exclusion criteria
will be randomized to 1 of 3 treatment groups as follows: 1.5 mg titrating to 3 mg OCA, 5 mg
titrating to 10 mg OCA, or placebo, in a 1:1:1 ratio. Subjects will administer
investigational product (IP) orally, once daily for 2 consecutive 12-week periods.

For the first 12 weeks, the subject's dose will be 1.5 mg OCA, 5 mg OCA, or placebo. After 12
weeks, the subject's dose will be titrated as follows, providing there are no limiting safety
or tolerability concerns in the opinion of the investigator, while maintaining the trial
blind: the 1.5 mg OCA treatment group will titrate to 3 mg, the 5 mg OCA treatment group will
titrate to 10 mg OCA, and the placebo group will remain on placebo. Double-blind treatment
will continue for a further 12 weeks at that dose.

Any subjects whose dose is not titrated, due to safety or tolerability concerns, will remain
on their starting treatment (1.5 mg OCA, 5 mg OCA, or placebo) for the remainder of the
double-blind phase to Week 24.

Randomization will be 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).

Inclusion Criteria:

- Male or female aged 18 to 75 years

- Must provide written informed consent and agree to comply with the trial protocol

- Must have a diagnosis of PSC (based on cholangiography at any point in time)

- Alkaline phosphatase (ALP) at Screening ≥ 2x ULN

- Total bilirubin at Screening < 2.5x ULN.

- For subjects with concomitant inflammatory bowel disease (IBD):

1. Colonoscopy (if subject has a colon) or other appropriate endoscopic procedure
within 12 months of Day 0 confirming no dysplasia or colorectal cancer

2. Subjects with Crohn's Disease (CD) must be in remission as defined by a Crohn's
Disease Activity Index (CDAI) <150.

3. Subjects with ulcerative colitis (UC) must either be in remission or have mild
disease. Remission is defined as a partial Mayo score of ≤2 with no individual
sub-score exceeding 1. Mild disease is defined as a partial Mayo score ≤3 with no
individual sub-score exceeding 1 point.

- For subjects 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/kg/day during this time.

- Subjects being administered biologic treatments (eg, anti-tumor necrosis factor (TNF)
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 subjects of childbearing potential must use ≥ 1 effective method
(≤1% failure rate) of contraception during the trial and until 4 weeks following the
last dose of IP (including long term safety extension doses).

Exclusion Criteria:

- 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 (e.g., beta
blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt
[TIPS])

- History of, or current, hepatorenal syndrome (type I or II) or Screening serum
creatinine > 2 mg/dL (178 μmol/L)

- Platelet count < 50 x 10⁹/L

- Current clinical evidence of dominant strictures that are 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 are not considered a safety risk in the opinion of the
Investigator might be 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 cirrhosis (PBC), alcoholic liver disease, non-alcoholic fatty liver disease
(NAFLD), autoimmune hepatitis, hepatitis B virus (unless seroconverted and no positive
Hepatitis B Virus DNA), 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 (HIV) 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 subject is on a
stable prophylaxis dose for at least 3 months prior to Day 0).

- Administration of the following medications is prohibited ≤ 6 months of Day 0 and
throughout the trial: fenofibrate or other fibrates and potentially hepatotoxic
medications (including α-methyl-dopa, sodium valproic acid, isoniazide, or
nitrofurantoin).

- IBD flare during Screening (up to and including Day 0), where "flare" is 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 has 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 (e.g., 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 subjects 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.
We found this trial at
34
sites
3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Principal Investigator: David Goldberg, MD
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: Gautham Reddy, MD
Phone: 773-702-4477
University of Chicago One of the world's premier academic and research institutions, the University of...
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1200 Moursund Street
Houston, Texas 77030
(713) 798-4951
Principal Investigator: John Vierling, MD, FACP
Phone: 832-355-7608
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
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4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
(412) 624-4141
Principal Investigator: Michael Dunn, MD
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
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601 Elmwood Avenue
Rochester, New York 14642
(585) 275-2100
Principal Investigator: Benedict Maliakkal, MD
Univ of Rochester Medical Center One of the nation's top academic medical centers, the University...
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Sacramento, California 95814
Principal Investigator: Christopher Bowlus, MD
Phone: 916-734-8985
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Atlanta, Georgia 30309
Principal Investigator: Roshan Shrestha, MD
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13001 E. 17th Pl
Aurora, Colorado 80045
303-724-5000
Principal Investigator: Lisa Forman, MD
Phone: 303-724-1866
University of Colorado Denver The University of Colorado Denver | Anschutz Medical Campus provides a...
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345 St Paul Pl
Baltimore, Maryland 21202
(410) 332-9000
Principal Investigator: Paul Thuluvath, MD
Phone: 410-576-5485
Mercy Medical Center "Mercy Medical Center" is a hospital located in Baltimore, Maryland. The landmark...
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Bethesda, Maryland 21205
Principal Investigator: Zhipling Li, MD
Phone: 410-614-3169
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Bologna,
Principal Investigator: Pietro Andreone
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1653 W. Congress Parkway
Chicago, Illinois 60612
(312) 942-5000
Principal Investigator: Nancy Reau, MD
Phone: 312-942-1372
Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
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Cleveland, Ohio 44194
Principal Investigator: Pierre Gholam, MD
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281 W. Lane Ave
Columbus, Ohio 43210
(614) 292-6446
Principal Investigator: James Hanje, MD
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Dallas, Texas 75203
Principal Investigator: Parvez Mantry, MD
Phone: 214-947-1288
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Dallas, Texas 75246
Principal Investigator: Jacqueline O'Leary, MD
Phone: 214-818-7623
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Detroit, Michigan 48202
Principal Investigator: Stuart Gordon, MD
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Gainesville, Florida 32610
Principal Investigator: Cynthia Levy, MD
Phone: 352-243-4639
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Houston, Texas 77030
Principal Investigator: Victor Ankoma-Sey, MD
Phone: 713-799-2667
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340 W 10th St #6200
Indianapolis, Indiana 46202
(317) 274-3772
Principal Investigator: Raj Vuppalanchi, MD
Phone: 317-278-6266
Indiana University School of Medicine With more than 2,000 students in 2013, the Indiana University...
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Jackson, Mississippi 39216
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500 S Preston St
Louisville, Kentucky
(502) 852-5555
Principal Investigator: Matthew Cave, MD
Phone: 502-852-3383
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Marietta, Georgia 30060
Principal Investigator: Aasim M Sheikh, MD
Phone: 678-819-4217
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New Orleans, Louisiana 70112
Principal Investigator: Fredric Regenstein, MD
Phone: 504-988-6902
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New York, New York 10065
Principal Investigator: Sonal Kumar, MD
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1428 Madison Ave
New York, New York 10029
(212) 241-6500
Principal Investigator: Thomas Schiano, MD
Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai is...
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Phoenix, Arizona 85013
Principal Investigator: Anita Kohli, MD
Phone: 602-406-3614
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5777 East Mayo Boulevard
Phoenix, Arizona 85054
(480) 515-6296
Principal Investigator: Elizabeth Carey, MD
Phone: 480-342-2536
Mayo Clinic Mayo Clinic's campus in Arizona provides medical care for thousands of people from...
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Richmond, Virginia 23249
Principal Investigator: Velimir Luketic, MD
Phone: 804-675-6924
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Rochester, Minnesota 55905
Principal Investigator: Nicholas LaRusso, MD
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Saint Louis, Missouri 63104
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
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Seattle, Washington 98104
Principal Investigator: Kris Kowdley, MD
Phone: 206-386-2427
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Southlake, Texas 76092
Principal Investigator: Jacqueline O'Leary, MD
Phone: 817-310-4480
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