A study of Obeticholic Acid versus Placebo in Patients with Primary Biliary Cirrhosis plus long term extension study only with Obeticholic Acid

• Register: EUCTR
• Last refreshed on: 11 May 2020
• Main ID: EUCTR2011-004728-36-SE
• Date of registration: 16/02/2012
• Prospective Registration: Yes
• Primary sponsor: Intercept Pharmaceuticals, Inc.
• Public title: A study of Obeticholic Acid versus Placebo in Patients with Primary Biliary Cirrhosis plus long term extension study only with Obeticholic Acid
• Scientific title: A Phase 3, Double Blind, Placebo Controlled Trial and Long Term Safety Extension of Obeticholic Acid in Patients with Primary Biliary Cirrhosis
• Date of first enrolment: 16/04/2012
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004728-36
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services

Key inclusion & exclusion criteria

Inclusion criteria:
1. Definite or probable PBC diagnosis (consistent with AASLD and EASL Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of = 2 of the following 3 diagnostic factors:
-History of elevated ALP levels for at least 6 months
-Positive AMA titer or PBC specific antibodies
-Liver biopsy consistent with PBC
2. At least 1 of the following qualifying biochemistry values:
- ALP=1.67x ULN
-Total bilirubin > ULN but < 2x ULN
3. Age =18 years
4. Taking UDCA for at least 12 months (stable dose for = 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for = 3 months) prior to Day 0
5. Contraception: Female patients of childbearing potential must use = 1
effective (= 1% failure rate) method of contraception during the trial and for 30 days after the End of Treatment (EOT) visit.
6. Must provide written informed consent and agree to comply with the trial protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
Patients will be excluded from the trial if they meet any of the following:
1. History or presence of other concomitant liver diseases including:
-Hepatitis C virus (HCV) infection; patients with active hepatitis B (HBV)
infection will be excluded, however, patients who have seroconverted
(HbsAg and Hbe Ag negative) may be included after consultation with the medical monitor.
-Primary sclerosing cholangitis (PSC)
-Alcoholic liver disease
-Definite autoimmune liver disease or overlap hepatitis
-Nonalcoholic steatohepatitis (NASH)
-Gilbert’s Syndrome (exclusion due to interpretability of bilirubin levels)
2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
-History of liver transplantation, current placement on a liver transplant list or current MELD score = 15
-Portal hypertention 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]), or hepatic
encephalopathy
-Cirrhosis with complications, including history or presence of: spontaneous
-Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 µmol/L) bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN
3. Patients with severe pruritus or those requiring systemic treatment
for pruritus (e.g., with bile acid sequestrants [BAS] or rifampicin) within
2 months of Day 0 will be excluded.
4. Administration of the following medications is prohibited as specified below:
-Prohibited 6 months prior to Day 0 and throughout the trial (i.e., to last dose and/or EOT): azathioprine, colchicine, cyclosporine, methotrexate,
mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates;
budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including a-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)
-Prohibited 12 months prior to Day 0 and throughout the trial (i.e., to last dose and/or EOT): antibodies or immunotherapy directed against interleukins or other cytokines or chemokines
5. Patients who have previously participated in a clinical trial of OCA will not be allowed to participate.
6. History or presence of clinically concerning cardiac arrhythmias likely
to affect survival during the trial, or prolongation of Screening
(pretreatment) QT or QTc interval of > 500 milliseconds (msec).
7. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating


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

Health Condition(s) or Problem(s) studied

Primary biliary cirrhosis
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)

Trade Name: Ocaliva
Product Name: OCA (INT-747)
Product Code: OCA (INT-747)
Pharmaceutical Form: Tablet
INN or Proposed INN: Obeticholic acid
CAS Number: 459789-99-2
Current Sponsor code: OCA, 6-ECDCA or INT-747
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

Trade Name: Ocaliva
Product Name: OCA (INT-747)
Product Code: OCA (INT-747)
Pharmaceutical Form: Tablet
INN or Proposed INN: Obeticholic acid
CAS Number: 459789-99-2
Current Sponsor code: OCA, 6-ECDCA or INT-747
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the effects of OCA in patients with PBC on:
-Serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint
-Safety

Secondary Objective: To assess the effects of OCA in patients with PBC on:
-Hepatocellular injury and liver function, including histology (inflammatory,
structural [portal, parenchymal] and fibrotic assessments)
-Disease specific symptoms
-Biomarkers and noninvasive assessments of liver fibrosis
-Bile acids (BA)
-Other exploratory evaluations

Timepoint(s) of evaluation of this end point: Time expected for all patients to be enrolled: Approximately 12 months

Duration of individual patient participation: 12 months during the DB
phase; Up to 5 years (60 months) in the LTSE

Total duration of trial (excluding data collection and analysis):
DB phase: 24 months (2 years) with open label LTSE phase: 84 months
(7 years)

Primary end point(s): Primary Endpoint (evaluated as a responder analysis):
ALP < 1.67x ULN and total bilirubin within normal limits (WNL), and
ALP decrease of = 15% (to exclude clinically insignificant ALP changes)

Secondary Outcome(s)

Secondary end point(s): Analyses regarding secondary endpoints will be specified in the SAP and conducted for the following parameters. It is anticipated that additional disease prognostic algorithms will be published during the course of the trial. Where appropriate, secondary analyses will be conducted using such algorithms. At the blinded data review a determination will be made as to which algorithms will be evaluated statistically, as it is likely that there will be small numbers of patients for some algorithms and formal statistical analysis will not therefore be appropriate.

• ALP response rates of 10%, 20% and 40% change
• Disease Prognostic Risk (criteria in relevant patients):
-ALP = 3x ULN and AST = 2x ULN and normal bilirubin
- ALP = 1.5x ULN and AST = 1.5x ULN and bilirubin within normal limits
- ALP = 1.67x ULN and normal bilirubin
- Normal bilirubin and normal albumin
• Clinical laboratory values:
- GGT, ALT, AST, total and conjugated bilirubin
- Albumin, prothrombin time and INR
• Liver biopsy/histology: Inflammatory, structural (portal, parenchymal) and fibrotic assessments
• Disease Specific Symptoms:
- PBC-40
- 5-D Pruritus Questionnaire
- Pruritus VAS
• Biomarkers and non-invasive assessments of liver fibrosis
- Fibrosis biomarkers (ELF)
- TE (at selected trial sites)
- Other analytes: TNF-a, TGF-ß, IL-6, CK-18 and lysophosphatidic acid
• Bile acids
- Plasma OCA, other bile acids and conjugate concentrations
- Bile and feces concentrations (at selected trial sites)

Secondary ID(s)

747-301

2011-004728-36-BE

NCT01473524

Source(s) of Monetary Support

Intercept Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 16/04/2012
Contact: