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

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ClinicalTrials.gov Identifier: NCT02516605
Recruitment Status : Recruiting
First Posted : August 6, 2015
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Primary Biliary Cholangitis Drug: Part 1: LJN452 Drug: Part 1: Placebo Drug: Part 2: LJN452 Dose level 1 Drug: Part 2: Placebo Drug: Part 2: LJN452 Dose level 2 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 163 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : September 9, 2015
Estimated Primary Completion Date : February 18, 2020
Estimated Study Completion Date : February 18, 2020


Arm Intervention/treatment
Experimental: LJN452 Drug: Part 1: LJN452
LJN452 capsules administered once daily for 28 days
Other Name: tropifexor
Drug: Part 2: LJN452 Dose level 1
LJN452 capsules administered once a day for 12 weeks
Other Name: tropifexor
Drug: Part 2: LJN452 Dose level 2
LJN452
Other Name: tropifexor
Placebo Comparator: Placebo Drug: Part 1: Placebo
Matching placebo capsules administered once daily for 28 days
Drug: Part 2: Placebo
Matching placebo to LJN452 administered once a day for 12 weeks



Primary Outcome Measures :
  1. Change in cholestatic markers from baseline [ Time Frame: Baseline, Part 1 at 28 Days ]
    Evaluate the change in cholestatic markers following administration of LJN452

  2. Number of patients with adverse events, serious adverse events and death [ Time Frame: end of study 12 weeks ]
    Determine safety and tolerability of LJN452

  3. Change in cholestatic markers from baseline [ Time Frame: Baseline, Part 2 at 12 weeks ]
    Evaluate the change in cholestatic markers following administration of LJN452


Secondary Outcome Measures :
  1. Change from baseline in disease specific quality of life [ Time Frame: Baseline, Part 1: 28 days, Part 2: 12 weeks ]
    Evaluate change in quality of life using PBC-40 PRO

  2. Change from baseline in itch as determined by the itch domain in the PBC-40 [ Time Frame: Baseline, Part 1: 28 days, Part 2: 12 weeks ]
    Evaluate the change in itch using the itch domain in the PBC-40

  3. Change from baseline in itch as determined by 10mm VAS [ Time Frame: Baseline, Part 1: 28 days, Part 2: 12 weeks ]
    Evaluate the change in itch from baseline with a 10 mm VAS

  4. Part 1: Area under the plasma concentration-time profile (AUCtau) [ Time Frame: Day 1, Day 28 ]
    Evalaute AUCtau

  5. Part 1: Maximum plasma concentration of LJN452 (Cmax) [ Time Frame: Baseline, 28 days ]
    Evaluate Cmax

  6. Minimum plasma concentration of LJN452 (Cmin) [ Time Frame: Baseline, Part 1: 28 days, Part 2: 12 weeks ]
    Evaluate Cmin

  7. Average steady state plasma concentration following multiple doses of LJN452 (Cav,ss) [ Time Frame: Baseline, Part 1: 28 days, Part 2: 12 weeks ]
    Evaluate Cav,ss

  8. Part 1: Time to reach maximum concentration after durg administration (Tmax) [ Time Frame: Day 1, Day 28 ]
    Evalute Tmax


Other Outcome Measures:
  1. Part 2: determine the dose response relationship of LJN452 on ALP [ Time Frame: 12 weeks ]
    To determine the dose response relationship of LJN452 on ALP in patients with PBC following 12 weeks of treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of PBC as demonstrated by the presence of ≥ 2 of the following 3 diagnostic criteria:
  • History of Alkaline Phosphatase elevated above upper limit of normal for at least 6 months
  • Positive anti-mitochondrial 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 consistent with PBC
  • At least 1 of the following markers of disease severity:
  • ALP ≥ 1.67× upper limit of normal (ULN)
  • Total bilirubin > ULN but < 1.5× ULN In addition, patients must meet the following biochemical criteria at enrollment

    • ALT or AST ≤ 5 × ULN
    • Total bilirubin ≤ 1.5 × ULN
    • INR ≤ ULN
  • Subjects 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/m^2. BMI = Body weight (kg) / [Height (m)]^2.
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study.

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 during dosing and for 30 days following end of treatment.
  • History or 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 other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment
  • Elevated liver function tests at screening defined as follows:

    • potential Hy's Law case (defined as ALT or AST > 3 × ULN and TBL > 2 × ULN without notable increase in ALP to > 2 × ULN) or
    • ALT or AST > 3 × ULN combined with INR > 1.5.
    • Total bilirubin > ULN combined with albumin outside of the normal range.
  • Currently taking obeticholic acid or have taken obeticholic acid within 30 days of Randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02516605


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

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Sponsors and Collaborators
Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02516605     History of Changes
Other Study ID Numbers: CLJN452X2201
2015-001590-41 ( EudraCT Number )
First Posted: August 6, 2015    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Primary Biliary Cirrhosis, PBC
Primary Biliary Cholangitis

Additional relevant MeSH terms:
Cholangitis
Liver Cirrhosis, Biliary
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Liver Diseases
Liver Cirrhosis