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

NCT ID: NCT03517540

Last Updated: 2022-04-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

193 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-11

Study Completion Date

2020-10-15

Brief Summary

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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.

Detailed Description

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Conditions

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Non-alcoholic Steatohepatitis (NASH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Arm A: Tropifexor (LJN452) - Dose 1

tropifexor 140 mcg, once daily; given orally

Group Type EXPERIMENTAL

Tropifexor (LJN452)

Intervention Type DRUG

Comparison with monotherapy and different combination doses

Arm B: Cenicriviroc (CVC)

CVC 150 mg, once daily; given orally

Group Type EXPERIMENTAL

Cenicriviroc (CVC)

Intervention Type DRUG

Comparison with monotherapy and different combination doses

Arm C: Tropifexor (LJN452) Dose 1 + CVC

tropifexor 140 mcg + CVC 150 mg, once daily; given orally

Group Type EXPERIMENTAL

Tropifexor (LJN452)

Intervention Type DRUG

Comparison with monotherapy and different combination doses

Cenicriviroc (CVC)

Intervention Type DRUG

Comparison with monotherapy and different combination doses

Arm D: Tropifexor Dose 2 + CVC

tropifexor 90 mcg + CVC 150 mg, once daily; given orally

Group Type EXPERIMENTAL

Tropifexor (LJN452)

Intervention Type DRUG

Comparison with monotherapy and different combination doses

Cenicriviroc (CVC)

Intervention Type DRUG

Comparison with monotherapy and different combination doses

Interventions

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Tropifexor (LJN452)

Comparison with monotherapy and different combination doses

Intervention Type DRUG

Cenicriviroc (CVC)

Comparison with monotherapy and different combination doses

Intervention Type DRUG

Other Intervention Names

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LJN452 CVC

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Allergan

INDUSTRY

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Chandler, Arizona, United States

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Novartis Investigative Site

North Little Rock, Arkansas, United States

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Coronado, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Pasadena, California, United States

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Rialto, California, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Metairie, Louisiana, United States

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Shreveport, Louisiana, United States

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Concord, North Carolina, United States

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Durham, North Carolina, United States

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Morehead City, North Carolina, United States

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Providence, Rhode Island, United States

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Chattanooga, Tennessee, United States

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Germantown, Tennessee, United States

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Hermitage, Tennessee, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Murray, Utah, United States

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Richmond, Virginia, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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CABA, Buenos Aires, Argentina

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Caba, Buenos Aires, Argentina

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San Juan Bautista, Buenos Aires, Argentina

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Edegem, Antwerpen, Belgium

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Leuven, , Belgium

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Montreal, Quebec, Canada

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Prague, , Czechia

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Shebeen El-Kom, , Egypt

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Paris, , France

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Pessac, , France

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Strasbourg, , France

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Mainz, , Germany

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Würzburg, , Germany

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New Delhi, National Capital Territory of Delhi, India

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Tel Aviv, , Israel

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Modena, Itlay, Italy

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Palermo, PA, Italy

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Roma, RM, Italy

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Verona, VR, Italy

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Milan, , Italy

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Riga, , Latvia

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Moscow, , Russia

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Moscow, , Russia

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Singapore, , Singapore

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Singapore, , Singapore

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Santander, Cantabria, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Valencia, Valencia, Spain

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Pendik / Istanbul, Turkey, Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Novartis Investigative Site

High Heaton, Newcastle Upon Tyne, United Kingdom

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Novartis Investigative Site

Aberdeen, , United Kingdom

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Novartis Investigative Site

Torquay, , United Kingdom

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Countries

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United States Argentina Belgium Canada Czechia Egypt France Germany India Israel Italy Latvia Russia Singapore Spain Turkey (Türkiye) United Kingdom

References

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Pedrosa M, Seyedkazemi S, Francque S, Sanyal A, Rinella M, Charlton M, Loomba R, Ratziu V, Kochuparampil J, Fischer L, Vaidyanathan S, Anstee QM. A randomized, double-blind, multicenter, phase 2b study to evaluate the safety and efficacy of a combination of tropifexor and cenicriviroc in patients with nonalcoholic steatohepatitis and liver fibrosis: Study design of the TANDEM trial. Contemp Clin Trials. 2020 Jan;88:105889. doi: 10.1016/j.cct.2019.105889. Epub 2019 Nov 13.

Reference Type RESULT
PMID: 31731005 (View on PubMed)

Parthasarathy G, Malhi H. Macrophage Heterogeneity in NASH: More Than Just Nomenclature. Hepatology. 2021 Jul;74(1):515-518. doi: 10.1002/hep.31790. Epub 2021 May 22. No abstract available.

Reference Type DERIVED
PMID: 33666272 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=984

A Plain Language Trial Summary is available on novctrd.com

Other Identifiers

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2017-004208-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LJC242A2201J

Identifier Type: OTHER

Identifier Source: secondary_id

CLJC242A2201J

Identifier Type: -

Identifier Source: org_study_id

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