A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients

Novartis Pharmaceuticals61 enrolled

Overview

A multi-part study to assess safety, tolerability and efficacy of tropifexor (LJN452) in patients with primary biliary cholangitis

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Primary Biliary Cholangitis

Interventions

Part 1: LJN452DRUG

LJN452 capsules administered once daily for 28 days

Part 1: PlaceboDRUG

Matching placebo capsules administered once daily for 28 days

Part 2: LJN452 Dose level 1DRUG

LJN452 capsules administered once a day for 12 weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Diagnosis of PBC as demonstrated by the presence of at least 2 of the following 3 diagnostic criteria: * History of alkaline phosphatase (ALP) elevated above upper limit of normal (ULN) for at least 6 months * Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in 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)) * Previous liver biopsy findings consistent with PBC * At least 1 of the following markers of disease severity: * ALP ≥ 1.67 × ULN * Total bilirubin \> ULN but \< 1.5 × ULN * In addition, patients must meet the following biochemical criteria at enrollment: * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 × ULN * Total bilirubin ≤ 1.5 × ULN * INR ≤ ULN * Taking UDCA for at least 12 months, or for at least 6 months and has reached maximal response to UDCA with a plateau in alkaline phosphatase, with no changes in dose for ≥ 3 months prior to Day 1. * Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 40 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2 Exclusion Criteria: * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception for 30 days before randomization, during dosing and for 30 days following the end of treatment. * Presence of other concomitant liver diseases. * Cirrhosis with complications, including history or presence of: * Variceal bleed * Uncontrolled ascites * Encephalopathy * Spontaneous bacterial peritonitis * Significant hepatic impairment as defined by Child-Pugh classification of B or C, history of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15. * History of conditions that may cause increases in ALP (e.g., Paget's disease). * Use of investigational drugs, or immunosuppressive drugs at the time of enrollment, or within 5 half-lives, or 30 days of randomization, whichever is longer; or longer if required by local regulations. Use of high dose oral steroids to treat co-morbid conditions (e.g., airways disease) will be allowed but must be properly documented as such in concomitant medications. * Currently taking obeticholic acid or have taken obeticholic acid within 30 days of randomization * Previous participation in CLJN452X2201 and received study medication within three months of randomization (or longer if required by local regulations).

Locations (28)

Novartis Investigative Site

Outcomes

Primary Outcomes

Fold Change in Serum Gamma-glutamyl Transferase (GGT)

Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28

Time frame: Baseline to Day 28

Blood Pressure

Vital signs - Systolic Blood pressure

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Pulse Rate

Vital signs

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Body Temperature

Vital signs

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

ECG - Heart Rate

Electrocardiogram (ECG)

Time frame: Screening, Baseline, day 1, day 28

ECG Intervals - PR Interval

Electrocardiogram (ECG)

Time frame: Screening, Baseline, day 1, day 28

Haemoglobin

Hematology panel for safety laboratory assessments.

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Secondary Outcomes

Plasma PK Parameter - AUC 0-8h

Tropifexor levels were determined in plasma using a validated LC-MS/MS method. AUC0-t=The area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration \[mass x time / volume\]

Data from ClinicalTrials.gov

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