Study to determine if the investigational drug obeticholic acid (also known as OCA) in combination with the investigational drug bezafibrate (BZF), has an effect on Primary Biliary Cholangitis (also known as Primary Biliary Cirrhosis or PBC).

• Register: EUCTR
• Last refreshed on: 28 September 2020
• Main ID: EUCTR2018-002575-17-ES
• Date of registration: 26/07/2019
• Prospective Registration: Yes
• Primary sponsor: Intercept Pharmaceuticals, Inc.
• Public title: Study to determine if the investigational drug obeticholic acid (also known as OCA) in combination with the investigational drug bezafibrate (BZF), has an effect on Primary Biliary Cholangitis (also known as Primary Biliary Cirrhosis or PBC).
• Scientific title: A Phase 2, Double-Blind, Randomized, Parallel-Group Study Evaluating the Efficacy, Safety, and Tolerability of Obeticholic Acid, Administered Alone or in Combination with Bezafibrate, in Subjects with Primary Biliary Cholangitis who had an Inadequate Response or who were Unable to Tolerate Ursodeoxycholic Acid
• Date of first enrolment: 15/10/2019
• Target sample size: 54
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002575-17
• 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: yes; 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

Australia, Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Korea, Republic of, Latvia, Lithuania, Netherlands, Norway, Poland, Slovakia, Slovenia, Spain, Sweden, United Kingdom

Contacts

• Name: Pawel Waszka
• Affiliation: Syneos Health

• Name: Pawel Waszka
• Affiliation: Syneos Health

Key inclusion & exclusion criteria

Inclusion criteria:
- A definite or probable diagnosis of PBC (consistent with the European Association for the Study of the Liver [EASL] Practice Guidelines and the American Association for the Study of Liver Diseases; [Lindor 2009a, EASL 2017])
- Qualifying ALP and bilirubin liver biochemistry values
- Age =18 years
- Taking UDCA for at least 12 months (stable dose for =3 months) before Day 1 or unable to tolerate or unresponsive to UDCA (no UDCA for =3 months) before Day 1
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
- History or presence of other concomitant liver diseases
- Presence of clinical complications of PBC or clinically significant (CS) hepatic decompensation
- Current or history of gallbladder disease with or without cholelithiasis
- Severe renal failure (serum creatinine >1.5 mg/100 mL (>135 µmol/L); creatinine clearance <60 mL/min) or undergoing dialysis
- Severe pruritus, or required systemic treatment for pruritus (eg, with bile acid sequestrants or rifampicin) within 2 months of Day 1
- History of known or suspected CS hypersensitivity to OCA, BZF, or other fibrates or any of their components
- Was treated with commercially available OCA or participated in a previous study involving OCA within 1 year before Screening or plans to use commercially available OCA during the study
- Is unable to tolerate BZF or other fibrates, was treated with commercially available fibrates or participated in a previous study involving fibrates within 3 months before Screening, or plans to use commercially available fibrates during the study

Note: Other protocol defined Inclusion/Exclusion criteria may apply


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

Health Condition(s) or Problem(s) studied

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

Primary Biliary Cholangitis (PBC) in patients with Inadequate Response or who were Unable to Tolerate Ursodeoxycholic Acid
MedDRA version: 21.0 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871

Intervention(s)

Trade Name: Ocaliva 10mg
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-

Trade Name: Ocaliva 5mg
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-

Trade Name: Bezalip
Product Name: Bezafibrate IR
Pharmaceutical Form: Tablet
INN or Proposed INN: BEZAFIBRATE
CAS Number: 41859-67-0
Other descriptive name: Bezafibrate, Beza, BZF, Bezalip
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Bezalip mono
Product Name: Bezafibrate SR
Pharmaceutical Form: Tablet
INN or Proposed INN: BEZAFIBRATE
CAS Number: 41859-67-0
Other descriptive name: Bezafibrate, Beza, BZF, Bezalip mono
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective is to assess the effects of the combination of OCA and BZF on alkaline phosphatase (ALP) in comparison to OCA alone in subjects with PBC who had an inadequate response or who were unable to tolerate ursodeoxycholic acid (UDCA).

Timepoint(s) of evaluation of this end point: week 12

Primary end point(s): Absolute change in ALP from baseline to Week 12 in the DB Treatment Period

Secondary Objective: The secondary objectives are to assess the effects of the combination of OCA and BZF in comparison to OCA alone in subjects with PBC who had an inadequate response or who were unable to tolerate UDCA on the following:
- Safety and tolerability
- Response and normalization rates of biochemical disease markers
- Disease-specific symptoms as assessed by health-related quality of life questionnaires
- Biomarkers of bile acid synthesis and homeostasis

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to End of study

Secondary end point(s): - Safety and tolerability
- Response and normalization rates of biochemical disease markers
- Disease-specific symptoms as assessed by health-related quality of life questionnaires
- Biomarkers of bile acid synthesis and homeostasis

Secondary ID(s)

2018-002575-17-HU

747-213

Source(s) of Monetary Support

Intercept Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 19/09/2019
Contact: