A Study of Efficacy and Safety of Ustekinumab in Patients with Primary Biliary Cirrhosis (PBC) Who had an Inadequate Response to Ursodeoxycholic Acid

• Register: EUCTR
• Last refreshed on: 24 February 2014
• Main ID: EUCTR2011-000554-31-SE
• Date of registration: 16/08/2011
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study of Efficacy and Safety of Ustekinumab in Patients with Primary Biliary Cirrhosis (PBC) Who had an Inadequate Response to Ursodeoxycholic Acid
• Scientific title: A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy and Safety of Ustekinumab in Subjects with Primary Biliary Cirrhosis Who had an Inadequate Response to Ursodeoxycholic Acid (UDCA) - PURIFI
• Date of first enrolment: 26/10/2011
• Target sample size: 128
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000554-31
• 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: 3

Countries of recruitment

Canada, France, Germany, Italy, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
Have proven or are likely to have PBC; Be on a stable dose of ursodeoxycholic acid for at least 6 months prior to Week 0;Have screening ALP level > 1.67 ULN; Have screening laboratory test results within protocol-specified limits; Have no history of latent or active TB prior to screening and no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
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 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion criteria:
Has history of gastrointestinal bleeding, secondary to portal hypertension, hepatic encephalopathy, or ascites requiring treatment with diuretics; Has a screening direct bilirubin > 1.0 mg/dL; Has a previous liver histology with a diagnosis of steatohepatitis or has a high risk of nonalcoholic steatohepatitis; Has a previous liver histology with a diagnosis of chronic autoimmune hepatitis or has a high risk of autoimmune hepatitis overlap syndrome; Testing positive for surface antigen (HBsAg+), regardless of the results of other hepatitis B tests; Have used colchicine, methotrexate (MTX), azathioprine (AZA), or systemic corticosteroids within 3 months prior to the first administration of study drug.


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Primary Biliary Cirrhosis
MedDRA version: 14.1 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871

Intervention(s)

Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: N/A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: This is a Phase 2 study that is divided into 2 parts. Part 1 is an open-label, proof-of-concept study. Part 2 is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study evaluating the efficacy and safety of ustekinumab in subjects with PBC who had an inadequate response to UDCA.

PART 1: Open Label
Primary Objectives:
• To evaluate the efficacy of ustekinumab in reducing alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin in subjects with PBC.
• To determine the ustekinumab regimen(s), based on safety and efficacy, for development in Part 2.

PART 2: Double-blind
Primary Objectives:
• To evaluate the efficacy of ustekinumab in achieving ALP response (a decrease from baseline of > 40% in ALP) in subjects with PBC who had an inadequate response to UCDA.
• To evaluate the safety of ustekinumab in subjects with PBC.

Secondary Objective: PART 2: Double-blind
Secondary Objectives:
• To evaluate the efficacy of ustekinumab in reducing ALP, ALT, AST, and total bilirubin.
• To evaluate improvement in liver fibrosis as measured by the Enhanced Liver Fibrosis (ELF) test.
• To evaluate improvement in liver histology as measured by the modified Hepatic Activity Index (HAI).
• To evaluate the efficacy of ustekinumab in reducing cholestasis as measured by serum bile acid concentrations.
• To evaluate pharmacokinetics, immune response (IR), and pharmacodynamics of ustekinumab.
• To evaluate ustekinumab in improving fatigue, pruritus, and quality of life.
• To evaluate the effect ustekinumab has on long-term disease progression (death, transplant, cirrhosis, doubling of bilirubin).

Timepoint(s) of evaluation of this end point: Week 28

Primary end point(s): The primary endpoint is ALP response at Week 28 as defined by a decrease from baseline of > 40% in ALP.

Secondary Outcome(s)

Secondary end point(s): The major secondary endpoints by order of importance are:

1. Modified Corpechot Response at Week 28 as defined by ALP = 3 x ULN, AST = 2 x ULN, total bilirubin = 1 mg/dL for subjects with a total bilirubin = 1 mg/dL at baseline, and > 40% decrease from baseline in ALP. Subjects with total bilirubin >1 mg/dL at baseline will only be considered responders provided that the direct bilirubin value does not increase;

2. Change from baseline in ELF score at Week 28;

3. Change from baseline in the modified HAI at Week 28, in subjects with biopsies;

4. Change from baseline in the total serum bile acid concentrations at Week 28.

Timepoint(s) of evaluation of this end point: Week 28

Secondary ID(s)

2011-000554-31-GB

CNTO1275PBC2001

Source(s) of Monetary Support

Janssen Research & Development, a division of JJPRD, LLC