A clinical trial where neither the doctor, patient or sponsor know whether a placebo or active medicine is being given to the patient with cirrhosis to see if the medicine is safe in the treatment of that disease and to see how study drug is absorbed, distributed through the body and excreted out of the body.

• Register: EUCTR
• Last refreshed on: 26 July 2021
• Main ID: EUCTR2017-001762-13-BE
• Date of registration: 14/08/2018
• Prospective Registration: Yes
• Primary sponsor: Intercept Pharmaceuticals, Inc.
• Public title: A clinical trial where neither the doctor, patient or sponsor know whether a placebo or active medicine is being given to the patient with cirrhosis to see if the medicine is safe in the treatment of that disease and to see how study drug is absorbed, distributed through the body and excreted out of the body.
• Scientific title: A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients with Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment
• Date of first enrolment: 24/10/2018
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001762-13
• 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): yes

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Estonia, Germany, Hungary, Italy, Lithuania, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Giovana Blanco Almanza
• Affiliation: Syneos Health

• Name: Giovana Blanco Almanza
• Affiliation: Syneos Health

Key inclusion & exclusion criteria

Inclusion criteria:
1. A definite or probable diagnosis of PBC (consistent with American Association for the Study of Liver Diseases [AASLD] and European Association for the Study of the Liver [EASL] Practice Guidelines, defined as having =2 of the following 3 diagnostic factors:
• History of elevated ALP levels for at least 6 months
• Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer (=1:80), PBC specific antibodies (anti-GP210 and/or anti-SP100) and/or antibodies against the major M2 components (PDC E2, 2-oxo-glutaric acid dehydrogenase complex)
• Liver biopsy consistent with PBC (collected at any time prior to Screening)
2. Evidence of cirrhosis including at least one of the following:
• Biopsy results consistent with PBC Stage 4
• Liver stiffness as assessed by TE Value =16.9kPa
• Clinical evidence in the absence of acute liver failure consistent with cirrhosis including: gastroesophageal varices, ascites, radiological evidence of cirrhosis (nodular liver or enlargement of portal vein and splenomegaly)
• Combined low platelet count (<140 000/mm3) with
- persistent decrease in serum albumin, or
- elevation in prothrombin time/INR (not due to antithrombotic agent use), or
- elevated bilirubin (2× ULN)
3. Satisfy the criteria of the modified CP classification for hepatic impairment during Screening:
• Moderate: CP-B (Scores 7 to 9) or
• Severe: CP-C (Scores 10 to12)
4. MELD score of 6 to 24 at Screening
5. Taking UDCA for at least 12 months (stable dose for =3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for =3 months)

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 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19

Exclusion criteria:
1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)
2. History of liver transplant or organ transplant
3. History of alcohol or drug abuse within 12 months prior to Screening
4. Current hepatic encephalopathy (as defined by a West Haven score of =2)
5. History or presence of other concomitant liver diseases including:
• Hepatitis C virus infection and RNA positive
• Active hepatitis B infection; however, patients who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the Medical Monitor
• Primary sclerosing cholangitis
• Alcoholic liver disease
• Definite autoimmune liver disease or overlap hepatitis
• Gilbert’s Syndrome
6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization


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

Health Condition(s) or Problem(s) studied

Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment

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

Intervention(s)

Trade Name: Ocaliva
Product Name: Obeticholic Acid
Product Code: INT-747, OCA
Pharmaceutical Form: Tablet
INN or Proposed INN: obeticholic acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA
Other descriptive name: 6 alpha-ethylchenodeoxycholic acid (6-EDCA), OCA, 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

Trade Name: Ocaliva
Product Name: Obeticholic Acid
Product Code: INT-747, OCA
Pharmaceutical Form: Tablet
INN or Proposed INN: obeticholic acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA
Other descriptive name: 6 alpha-ethylchenodeoxycholic acid (6-EDCA), oCA, 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

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 48

Main Objective: To evaluate the PK of OCA and its conjugates, glyco-OCA and tauro-OCA, and OCA metabolite glucuronide compared with placebo. To evaluate the safety and tolerability of OCA treatment compared with placebo

Primary end point(s): Primary Objective:
• To evaluate the pharmacokinetics (PK) of OCA and its conjugates, glyco-OCA and tauro-OCA, and metabolite OCA glucuronide compared with placebo
• To evaluate the safety and tolerability of OCA treatment compared with placebo

Secondary Objective: To evaluate the effect of OCA treatment compared to placebo on:
- The MELD score and its components
- CP score and its components
- Liver biochemistry including total and direct bilirubin, alkaline phosphatase (ALP), and aminotransferases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transaminase [GGT]), international normalized ratio (INR), creatinine, albumin, platelets
- Biomarkers of bile acid synthesis and homeostasis including fibroblast growth factor 19 (FGF-19), 7a-hydroxy-4-cholesten-3-one (C4), and plasma bile acids

Secondary Outcome(s)

Secondary end point(s): Secondary Objectives:
• To evaluate the effect of OCA treatment compared to placebo on:
- The model of end stage liver disease (MELD) score and its components
- Child-Pugh (CP) score and its components
- Liver biochemistry including total and direct bilirubin, alkaline phosphatase (ALP), and aminotransferases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transaminase [GGT]), international normalized ratio (INR), creatinine, albumin, platelets
- Biomarkers of bile acid synthesis and homeostasis including fibroblast growth factor 19 (FGF-19), 7a-hydroxy-4-cholesten-3-one (C4), and plasma bile acids

Timepoint(s) of evaluation of this end point: week 48

Secondary ID(s)

NCT03633227

2017-001762-13-ES

747-401

Source(s) of Monetary Support

Intercept Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 24/10/2018
Contact: