Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis (TANDEM)

April 27, 2022 updated by: Novartis Pharmaceuticals

A Randomized, Double-blind, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis

The purpose of this study was to assess the safety, tolerability, and efficacy of a combination treatment of tropifexor (LJN452) and cenicriviroc (CVC) in adult patients with nonalcoholic steatohepatitis (NASH) and liver fibrosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

193

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1280AEB
        • Novartis Investigative Site
      • Caba, Buenos Aires, Argentina, C1181ACH
        • Novartis Investigative Site
      • Florencio Varela, Buenos Aires, Argentina, C1073ABA
        • Novartis Investigative Site
  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Novartis Investigative Site
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, v6z 2k5
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M6H 3MI
        • Novartis Investigative Site
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H4A 3J1
        • Novartis Investigative Site
  • Czechia
      • Prague, Czechia, 128 08
        • Novartis Investigative Site
  • Egypt
      • Shebeen El-Kom, Egypt
        • Novartis Investigative Site
  • France
      • Paris Cedex 13, France, 75651
        • Novartis Investigative Site
      • Pessac Cedex, France, 33604
        • Novartis Investigative Site
      • Strasbourg, France, 67098
        • Novartis Investigative Site
  • Germany
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Wuerzburg, Germany, 97080
        • Novartis Investigative Site
  • India
    • Delhi
      • New Delhi, Delhi, India, 110070
        • Novartis Investigative Site
  • Israel
      • Tel Aviv, Israel, 6423906
        • Novartis Investigative Site
  • Italy
      • Milan, Italy, 20112
        • Novartis Investigative Site
    • Itlay
      • Modena, Itlay, Italy, 41126
        • Novartis Investigative Site
    • PA
      • Palermo, PA, Italy, 90127
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00168
        • Novartis Investigative Site
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
  • Latvia
      • Riga, Latvia, LV-1006
        • Novartis Investigative Site
  • Russian Federation
      • Moscow, Russian Federation, 101990
        • Novartis Investigative Site
      • Moscow, Russian Federation, 109544
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 169608
        • Novartis Investigative Site
      • Singapore, Singapore, 117549
        • Novartis Investigative Site
  • Spain
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46026
        • Novartis Investigative Site
  • Turkey
      • Izmir, Turkey, 35100
        • Novartis Investigative Site
      • Pendik / Istanbul, Turkey, 34899
        • Novartis Investigative Site
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZN
        • Novartis Investigative Site
      • Torquay, United Kingdom, TQ2 7AA
        • Novartis Investigative Site
    • Newcastle Upon Tyne
      • High Heaton, Newcastle Upon Tyne, United Kingdom, NE7 7DN
        • Novartis Investigative Site
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Novartis Investigative Site
    • Arkansas
      • North Little Rock, Arkansas, United States, 72117
        • Novartis Investigative Site
    • California
      • Coronado, California, United States, 92118
        • Novartis Investigative Site
      • Los Angeles, California, United States, 90048
        • Novartis Investigative Site
      • Los Angeles, California, United States, 90057
        • Novartis Investigative Site
      • Pasadena, California, United States, 91105
        • Novartis Investigative Site
      • Rialto, California, United States, 92377
        • Novartis Investigative Site
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Novartis Investigative Site
      • Atlanta, Georgia, United States, 30312
        • Novartis Investigative Site
      • Marietta, Georgia, United States, 30060
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • Novartis Investigative Site
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Novartis Investigative Site
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • Novartis Investigative Site
      • Shreveport, Louisiana, United States, 71103
        • Novartis Investigative Site
    • North Carolina
      • Concord, North Carolina, United States, 28027
        • Novartis Investigative Site
      • Durham, North Carolina, United States, 27710
        • Novartis Investigative Site
      • Morehead City, North Carolina, United States, 28557
        • Novartis Investigative Site
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Novartis Investigative Site
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Novartis Investigative Site
      • Germantown, Tennessee, United States, 38138
        • Novartis Investigative Site
      • Hermitage, Tennessee, United States, 37076
        • Novartis Investigative Site
    • Texas
      • Dallas, Texas, United States, 75208-2312
        • Novartis Investigative Site
      • San Antonio, Texas, United States, 78215
        • Novartis Investigative Site
    • Utah
      • Murray, Utah, United States, 84107
        • Novartis Investigative Site
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Novartis Investigative Site
      • Richmond, Virginia, United States, 23249
        • Novartis Investigative Site
    • Washington
      • Seattle, Washington, United States, 98104
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Written informed consent Male and female patients 18 years or older (at the time of the screening visit). Patients must weigh at least 50 kg (110 lb) and no more than 200 kg (440 lb) to participate in the study.

Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Adequate liver biopsy sample for evaluation by Central Reader. Presence of NASH as demonstrated by histologic evidence based on liver biopsy - NASH with fibrosis stage F2/F3, demonstrated on liver biopsy during the screening period. Alternatively, a historical biopsy can be used if performed within 6 months prior to screening.

Exclusion Criteria:

Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer.

History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.

Previous exposure to elafibranor, CVC, tropifexor, obeticholic acid (OCA), LMB763 or other FXR agonist.

Participated in a clinical trial and treated with any investigational product being evaluated for the treatment of liver fibrosis or NASH in the 6 months before screening.

Patients taking medications prohibited by the protocol. History of treated or untreated malignancy of any organ system, other than localized basal cell carcinoma of the skin or treated cervical intraepithelial neoplasia, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases .

Pregnant or nursing (lactating) women. Women of child-bearing potential. Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 g/day in females and more than 30 g/day in males, on average) and/or a score on the modified AUDIT questionnaire ≥ 8.

Inability to reliably quantify alcohol consumption. History or evidence of ongoing drug abuse, within the last 6 months prior to randomization.

Prior or planned (during the study) bariatric surgery. Uncontrolled diabetes defined as HbA1c ≥ 9% at screening Clinical evidence of hepatic decompensation or severe liver impairment. Previous diagnosis of other forms of chronic liver disease. Calculated eGFR less than 60 mL/min (using the MDRD formula). History of biliary diversion History of liver transplantation or planned liver transplant. Known positivity for HIV. History or current diagnosis of ECG abnormalities indicating significant risk of safety for the patient to participate.

History of inflammatory bowel disease. Patients who are not candidates for liver biopsy. Presence of cirrhosis on liver biopsy (F4 by NASH CRN System) or medical history Patients with an abnormal platelet count (referring to reference ranges from the central lab).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Tropifexor (LJN452) - Dose 1
tropifexor 140 mcg, once daily; given orally
Drug: Tropifexor (LJN452)
Comparison with monotherapy and different combination doses
Other Names:
  • LJN452
Experimental: Arm B: Cenicriviroc (CVC)
CVC 150 mg, once daily; given orally
Drug: Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses
Other Names:
  • CVC
Experimental: Arm C: Tropifexor (LJN452) Dose 1 + CVC
tropifexor 140 mcg + CVC 150 mg, once daily; given orally
Drug: Tropifexor (LJN452)
Comparison with monotherapy and different combination doses
Other Names:
  • LJN452
Drug: Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses
Other Names:
  • CVC
Experimental: Arm D: Tropifexor Dose 2 + CVC
tropifexor 90 mcg + CVC 150 mg, once daily; given orally
Drug: Tropifexor (LJN452)
Comparison with monotherapy and different combination doses
Other Names:
  • LJN452
Drug: Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses
Other Names:
  • CVC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: AEs were collected from first dose of study treatment until end of study treatment at week 48 and then up to maximum duration of 66 weeks

Occurrence of adverse events and serious adverse events

Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment and then up to 66 weeks
AEs were collected from first dose of study treatment until end of study treatment at week 48 and then up to maximum duration of 66 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Who Have at Least a One Point Improvement in Fibrosis
Time Frame: baseline to 48 Weeks
Efficacy of tropifexor + CVC in patients with Nonalcoholic steatohepatitis (NASH) with fibrosis stage F2/F3 as assessed by histological improvement after 48 weeks of treatment compared to monotherapies (tropifexor and CVC) compared to baseline biopsy
baseline to 48 Weeks
Proportion of Participants With Resolution of Steatohepatitis
Time Frame: baseline to 48 weeks
Efficacy of tropifexor + CVC in patients with Nonalcoholic steatohepatitis (NASH) with fibrosis stage F2/F3 as assessed by histological improvement after 48 weeks of treatment compared to monotherapies (tropifexor and CVC) compared to baseline biopsy
baseline to 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Collaborators

Allergan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2018

Primary Completion (Actual)

September 15, 2020

Study Completion (Actual)

October 15, 2020

Study Registration Dates

First Submitted

April 9, 2018

First Submitted That Met QC Criteria

April 24, 2018

First Posted (Actual)

May 7, 2018

Study Record Updates

Last Update Posted (Actual)

April 29, 2022

Last Update Submitted That Met QC Criteria

April 27, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLJC242A2201J
  • 2017-004208-24 (EudraCT Number)
  • LJC242A2201J (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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