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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02516605
• Date of registration: 04/08/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients
• Scientific title: A Multi-part, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Primary Biliary Cholangitis
• Date of first enrolment: September 9, 2015
• Target sample size: 61
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02516605
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Canada, Germany, Poland, Russian Federation, United Kingdom, United States

Key inclusion & exclusion criteria

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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Primary Biliary Cholangitis

Intervention(s)

Drug: Part 2: LJN452 Dose level 2

Drug: Part 2: LJN452 Dose level 1

Drug: Part 2: Placebo

Drug: Part 1: LJN452

Drug: Part 1: Placebo

Primary Outcome(s)

ECG - Heart Rate [Time Frame: Screening, Baseline, day 1, day 28]

Body Temperature [Time Frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84]

Blood Pressure [Time Frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84]

Haemoglobin [Time Frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84]

ECG Intervals - PR Interval [Time Frame: Screening, Baseline, day 1, day 28]

Fold Change in Serum Gamma-glutamyl Transferase (GGT) [Time Frame: Baseline to Day 28]

Pulse Rate [Time Frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84]

Secondary Outcome(s)

Changes From Baseline in Total PBC-40 Score [Time Frame: Baseline, Day 28, Day 56, Day 84]

Plasma PK Parameter - Tmax [Time Frame: Day 1, Day 28]

Change From Baseline in Global Itch Visual Analogue Scale (VAS) [Time Frame: Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84]

Plasma PK Parameter - AUC 0-8h [Time Frame: Day 1, Day 28]

Change From Baseline in Itch Subdomain of PBC-40 Score [Time Frame: Baseline, Day 28, Day 56, Day 84]

Plasma PK Parameter - Cmax [Time Frame: Day 1, Day 28]

Secondary ID(s)

CLJN452X2201

2015-001590-41

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/11/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02516605