A Study of Obeticholic Acid (OCA) in Patients with Primary Sclerosing Cholangitis

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2014-002205-38-IT
• Date of registration: 12/02/2018
• Prospective Registration: No
• Primary sponsor: INTERCEPT PHARMACEUTICALS INC.
• Public title: A Study of Obeticholic Acid (OCA) in Patients with Primary Sclerosing Cholangitis
• Scientific 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 - AESOP (Assessment of Efficacy and Safety of OCA in PSC)
• Date of first enrolment: 02/12/2015
• Target sample size: 75
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002205-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: OCA dose titration If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy, United States

Contacts

• Name: Regulatory Affairs
• Affiliation: Wainwright Associates Limited

• Name: Regulatory Affairs
• Affiliation: Wainwright Associates Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following to be eligible to participate:
1. Male or female aged 18 to 75 years
2. Must provide written informed consent and agree to comply with the trial protocol
3. Must have a diagnosis of PSC (based on cholangiography at any point
in time) and must have had a cholangiography within the past 12 months
4. ALP at Screening =2x ULN
5. Total bilirubin at Screening <2.5x ULN.
Note 1: Subjects will be stratified according to total bilirubin level and no
more than 25% of subjects recruited will have a total bilirubin >1.5x
ULN and <2.5x ULN at Screening.
6. For subjects with concomitant IBD:
a. Colonoscopy (if the subject has a colon) or other appropriate
endoscopic procedure within 12 months of Day 0 confirming
no
dysplasia or colorectal cancer
b. Subjects with Crohn's Disease (CD) must be in remission as defined
by a Crohn's Disease Activity Index (CDAI) <150.
c. 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.
7. 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.
Note 2: Subjects not taking UDCA at Day 0 must not have taken UDCA
for =3 months prior to, and including, Day 0 and must not take UDCA
during the DB period. Subjects will be stratified according to UDCA use and no more than 50% of subjects administering UDCA at Day 0 will be
enrolled.
8. Subjects being administered biologic treatments (eg, Anti-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.
9. 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 investigational
product
(including LTSE doses). Effective methods of contraception are considered to be those listed below:
• Double barrier method, ie, (a) condom (male or female) or (b) diaphragm, with spermicide; or
• Intrauterine device; or
• Vasectomy (partner), or
• Hormonal (e.g., contraceptive pill, patch,
• intramuscular implant or injection); or
• Abstinence, if in line with the preferred and usual lifestyle of the subject [where abstinence is defined as refraining from heterosexual
intercourse during the trial duration (from first
administration of investigational product until 4 weeks after the last dose of investigational product)]
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
1. Evidence of a secondary cause of sclerosing cholangitis at Screening
2. Immunoglobulin G4 (IgG4) >4x ULN at Screening or evidence of IgG4
sclerosing cholangitis
3. Small duct cholangitis in the absence of large duct disease
4. 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 (MELD) 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 (eg, 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 x10E9/L
5. Clinical evidence of dominant stricture (as evidenced by
cholangiography or other appropriate imaging modality within the 12
months prior to Day 0) or current biliary stent
6. Current cholecystitis or gallstones (identified by hepatic imaging)
7. Colonic dysplasia within =5 years prior to Day 0
8. History of small bowel resection
9. 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
10. Known Gilbert’s syndrome or elevations in unconjugated (indirect)
bilirubin >ULN
11. Known history of human immunodeficiency virus (HIV) infection
12. Currently experiencing, or experienced within =3 months of Screening,
pruritus requiring systemic or enteral treatment,
13. Known or suspected acute cholangitis in the 3 months prior to, and
including, Day 0 including cholangitis treated with antibiotics.
14. 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).
15. 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 a-methyl-dopa,
sodium valproic acid, isoniazide, or nitrofurantoin).
16. 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
17. 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)
18. Known or suspected use o

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary Sclerosing Cholangitis
MedDRA version: 20.0 Level: SOC Classification code 10019805 Term: Hepatobiliary disorders System Organ Class: 10019805 - Hepatobiliary disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: OCA 1,5 mg
Product Code: INT-747, OCA
Pharmaceutical Form: Tablet
INN or Proposed INN: ACIDO OBETICOLICO
CAS Number: 459789-99-2
Current Sponsor code: OCA
Other descriptive name: ACIDO OBETICOLICO
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: OCA 5 mg
Product Code: INT-747, OCA
Pharmaceutical Form: Tablet
INN or Proposed INN: ACIDO OBETICOLICO
CAS Number: 459789-99-2
Current Sponsor code: OCA
Other descriptive name: ACIDO OBETICOLICO
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objects are to evaluate the effects of OCA on the following in subjects with PSC:
• Hepatic biochemistry and indices of function
• Markers of:
- Hepatic fibrosis and GI inflammation and disease
- Farnesoid X receptor (FXR) activity
- Inflammatory bowel disease (IBD)
• Pharmacokinetics of OCA and other bile acids
• Exposure response of total OCA (OCA and its conjugates) to biomarkers (eg, ALP and bile acids)
• Long-term efficacy and safety of OCA
• Disease-specific symptoms.

Timepoint(s) of evaluation of this end point: 24 weeks of double-blind treatment

Main Objective: To evaluate the effects of OCA on the following in subjects with PSC:
- serum alkaline phosphatase (ALP)
- Safety

Primary end point(s): The primary efficacy endpoint is the change in ALP (from baseline to week 24)

Secondary Outcome(s)

Secondary end point(s): To evaluate the effects of OCA on the following in subjects with PSC:
• Hepatic biochemistry and indices of function
• Markers of:
- Hepatic fibrosis and GI inflammation and disease
- Farnesoid X receptor (FXR) activity
- Inflammatory bowel disease (IBD)
• Pharmacokinetics (PK) of OCA and other bile acids
• Exposure response of total OCA (OCA and its conjugates) to
biomarkers (eg, ALP and bile acids)
• Long-term efficacy and safety of OCA
• Disease-specific symptoms.

Timepoint(s) of evaluation of this end point: Baseline, week 12 & Week 24 of the double-blind phase.

Month 12 and month 24 in the extension open label phase.

Secondary ID(s)

747-207

NCT02177136

Source(s) of Monetary Support

Intercept Pharmaceuticals, Inc

Ethics review

Status: Approved
Approval date: 01/12/2015
Contact:

Results

• Results available: Yes
• Date Posted: 23/03/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002205-38/results