CTRI Number	CTRI/2018/06/014509 [Registered on: 12/06/2018] Trial Registered Prospectively
Last Modified On:	22/08/2020
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study Modification(s)	Drug
Study Design	Randomized, Parallel Group, Placebo Controlled Trial
Public Title of Study Modification(s)	A randomized, double blind, placebo controlled , multicenter, 12 weeks study to assess safety ,tolerability and efficacy of LJN452 in patients with non-alcoholic steatohepatitis
Scientific Title of Study Modification(s)	A randomized, double-blind, placebo controlled, 3- part, adaptive design, multicenter study to assess safety, tolerability and efficacy of tropifexor (LJN452) in patients with non-alcoholic steatohepatitis (NASH)
Secondary IDs if Any	Secondary ID  Registry  CLJN452A2202-NASH  Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Murugananthan K   Address  Novartis Healthcare Private Limited, Medical Department, Sandoz House, Shiv Sagar Estate, Dr. Annie Besant Road, Worli, Mumbai – 400 018 Mumbai MAHARASHTRA Mumbai MAHARASHTRA Mumbai MAHARASHTRA 400018 India  Phone  02224958545   Fax     Email  murugananthan.k@novartis.com
Details Contact Person Scientific Query Modification(s)	Name  Murugananthan K   Address  Novartis Healthcare Private Limited, Medical Department, Sandoz House, Shiv Sagar Estate, Dr. Annie Besant Road, Worli, Mumbai – 400 018 Mumbai MAHARASHTRA Mumbai MAHARASHTRA Mumbai MAHARASHTRA 400018 India  Phone  02224958545   Fax     Email  murugananthan.k@novartis.com
Details Contact Person Public Query Modification(s)	Name  Murugananthan K   Address  Novartis Healthcare Private Limited, Medical Department, Sandoz House, Shiv Sagar Estate, Dr. Annie Besant Road, Worli, Mumbai – 400 018 Mumbai MAHARASHTRA Mumbai MAHARASHTRA Mumbai MAHARASHTRA 400018 India  Phone  02224958545   Fax     Email  murugananthan.k@novartis.com
Source of Monetary or Material Support	Novartis Pharma AG, CH-4002 Basel, Switzerland.
Primary Sponsor	Name  Novartis Healthcare Pvt Ltd  Address  Medical Dept, Sandoz House, Shiv Sagar Estate, Dr. Annie Besant Road, Worli, Mumbai- 400018  Type of Sponsor  Pharmaceutical industry-Global
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	Australia Austria Belgium Canada France Germany India Italy Netherlands Slovakia Spain Switzerland Taiwan United States of America
Sites of Study Modification(s)	No of Sites = 5   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Manav Wadhawan  Fortis Escorts Heart Institute  Fortis Escorts Liver and Digestive Diseases Institute Fortis Escorts Heart Institute Okhla Road New Delhi-110025 India New Delhi   91244713500 91244713500 manavwadhawan@gmail.com  Dr Shah Samir Ramnik  Global Hospitals-Super Speciality & Transplant Centre  Dr E.Borges Road Hospital Avenue Opp Shirodkar High School Parel Mumbai400012 Maharashtra India Mumbai   912267670101 912267670101 drshahsamir@gmail.com  Dr Shiv Kumar Sarin  Institute of Liver and Biliary Sciences,   Institute of Liver and Biliary Sciences, Hepatology,D1, Vasant Kunj, Delhi 110070 New Delhi   9873173140 shivsarin@gmail.com  Dr Gaurav Mehta  Kokilaben Dhirubhai Ambani Hospital & Medical research Institute  Rao Saheb Achutrao Patwardhan Marg Four bunglows AndheriWest Mumbai 400 053 Maharshtra India Mumbai   0223099999 02230972030 gaurav.mehta@relianceada.com  Dr Arvinder Singh Soin  Medanta Institute of Liver Transplantation and Regenerative Medicine  Medanta The Medicity Sector 38 Gurugram 122001 Haryana Gurgaon   911244411441 91244834111 Arvinder.Soin@Medanta.org
Details of Ethics Committee Modification(s)	No of Ethics Committees= 5   Name of Committee  Approval Status  Ethics Committee Global Hospital Mumbai  Submittted/Under Review  Institution Scientific and Ethics Board Kokilaben Dhirubhai Ambani Hospital & Medical research Institute Rao Saheb Achutrao Patwardhan Marg Four bunglows Andheri West Mumbai 400 053  Approved  Institutional Ethics Committee Dr Wadhwan  Approved  Institutional Ethics Committee_Dr Sarin  Approved  Medanta Institutional Ethics Committee  Approved
Regulatory Clearance Status from DCGI Modification(s)	Status  Approved/Obtained
Health Condition / Problems Studied	Health Type  Condition  Patients  Non-alcoholic Steatohepatitis NASH
Intervention / Comparator Agent	Type  Name  Details  Intervention  Arm A LJN452 dose 1   Once daily (morning fasting) treatment with 10 μg LJN452 for 12 weeks  Intervention  Arm B  Once daily (morning fasting) treatment with 10 μg LJN452 for 12 weeks  Intervention  Arm C  Once daily (morning fasting) treatment with 10 μg LJN452 for 12 weeks  Intervention  Arm D  Once daily (morning fasting) treatment with 10 μg LJN452 for 12 weeks  Intervention  Arm E  Once daily (morning fasting) treatment with 10 μg LJN452 for 12 weeks  Comparator Agent  Arm F  Once daily (morning fasting) treatment with LJN452 dose A as determined after DMC review of first Part A interim analysis data for 12 weeks  Comparator Agent  Arm G  Once daily (morning fasting) treatment with LJN452 dose B as determined after DMC review of first Part A interim analysis data for 12 weeks  Comparator Agent  Arm H  Once daily (morning fasting) treatment with matching placebo for 12 weeks
Inclusion Criteria	Age From  18.00 Year(s) Age To  99.00 Year(s) Gender  Both  Details  1 male/female patients, 18 years or older 2 written informed consent 3 presence of NASH by histological evidence (liver biopsy) and elevated alanine aminotransferase (ALT) OR phenotypic diagnosis based on elevated ALT, BMI and diagnosis of Type 2 diabetes mellitus (DM) 4 Liver fat equal to or higher than 10% by MRI
ExclusionCriteria	Details  1 previous exposure to OCA 2 patients taking prohibited medications 3 pregnant or nursing (lactating) women 4 current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening 5 uncontrolled diabetes mellitus 6 presence of cirrhosis 7 hepatic decompensation or severe liver impairment 8 previous diagnosis of other forms of chronic liver disease 9 patients with contraindications to MRI imaging
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Centralized
Blinding/Masking	Participant and Investigator Blinded
Primary Outcome	Outcome  TimePoints  1 Adverse event profile of different doses of LJN452 in patients with NASH 2 Change in Transaminase levels   12 weeks
Secondary Outcome	Outcome  TimePoints  1 Change from baseline in percentage of fat in the liver assessed using MRI  12 weeks  2 Change from baseline in weight   12 weeks  Change from baseline in biomarker C4   12 weeks  Change from baseline in biomarker FGF19   12 weeks  Change from baseline in BMI   12 weeks  Change from baseline in waist-to-hip (WTH) ratio   12 weeks  Change from baseline on fasting lipid profile   12 weeks  Change from baseline on gamma-glutamyl transferase (GGT)  12 weeks  Change from baseline on on markers of liver fibrosis   12 weeks  Determine C2h of LJN452   12 weeks  Determine Ctrough of LJN452   12 weeks  Itch based on a visual analog scale (VAS) rating scale   12 weeks
Target Sample Size	Total Sample Size="250" Sample Size from India="50"
Phase of Trial	Phase 2
Date of First Enrollment (India) Modification(s)	14/06/2018
Date of First Enrollment (Global)	11/01/2018
Estimated Duration of Trial	Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Closed to Recruitment of Participants
Recruitment Status of Trial (India)	Closed to Recruitment of Participants
Publication Details	No publication provided
Brief Summary	1 Purpose of the trial The purpose of this study is to assess the safety and tolerability profile of LJN452 and to determine the early hepatic response to different doses of LJN452 in patien ts with phenotypic non-alcoholic steatohepatitis (NASH). Data from this study will be used to support further development of LJN452 in the treatment of patients with NASH. 2 FPFV for India : 4 Oct 2017 3 Target sample size for India  50