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

NCT03517540 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CLJC242A2201J2017-004208-24LJC242A2201J
• Study Type: interventional
• Target: 193
• Locations: 17 countries
• Sites: 65

Brief Summary

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.

Conditions

Non-alcoholic Steatohepatitis (NASH)

Keywords

Steatohepatitis; NASH; NAFLD; Fatty Liver Disease; Liver; Liver fibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  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 Outcomes (2)

• Proportion of Participants Who Have at Least a One Point Improvement in Fibrosis

  baseline to 48 Weeks

• Proportion of Participants With Resolution of Steatohepatitis

  baseline to 48 weeks

Study Arms (4)

Arm A: Tropifexor (LJN452) - Dose 1

EXPERIMENTAL

tropifexor 140 mcg, once daily; given orally

Drug: Tropifexor (LJN452)

Arm B: Cenicriviroc (CVC)

EXPERIMENTAL

CVC 150 mg, once daily; given orally

Drug: Cenicriviroc (CVC)

Arm C: Tropifexor (LJN452) Dose 1 + CVC

EXPERIMENTAL

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

Drug: Tropifexor (LJN452); Drug: Cenicriviroc (CVC)

Arm D: Tropifexor Dose 2 + CVC

EXPERIMENTAL

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

Drug: Tropifexor (LJN452); Drug: Cenicriviroc (CVC)

Interventions

Tropifexor (LJN452) DRUG

Comparison with monotherapy and different combination doses

Also known as: LJN452

Arm A: Tropifexor (LJN452) - Dose 1; Arm C: Tropifexor (LJN452) Dose 1 + CVC; Arm D: Tropifexor Dose 2 + CVC

Cenicriviroc (CVC) DRUG

Comparison with monotherapy and different combination doses

Also known as: CVC

Arm B: Cenicriviroc (CVC); Arm C: Tropifexor (LJN452) Dose 1 + CVC; Arm D: Tropifexor Dose 2 + CVC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Allergan: collaborator

Study Sites (65)

Novartis Investigative Site

Chandler, Arizona, 85224, United States

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Novartis Investigative Site

North Little Rock, Arkansas, 72117, United States

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Coronado, California, 92118, United States

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Los Angeles, California, 90048, United States

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Los Angeles, California, 90057, United States

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Pasadena, California, 91105, United States

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Rialto, California, 92377, United States

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Atlanta, Georgia, 30309, United States

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Atlanta, Georgia, 30312, United States

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Marietta, Georgia, 30060, United States

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Chicago, Illinois, 60637-1470, United States

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Indianapolis, Indiana, 46237, United States

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Metairie, Louisiana, 70006, United States

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Shreveport, Louisiana, 71103, United States

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Concord, North Carolina, 28027, United States

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Durham, North Carolina, 27710, United States

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Morehead City, North Carolina, 28557, United States

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Providence, Rhode Island, 02905, United States

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Chattanooga, Tennessee, 37404, United States

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Germantown, Tennessee, 38138, United States

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Hermitage, Tennessee, 37076, United States

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Dallas, Texas, 75208-2312, United States

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San Antonio, Texas, 78215, United States

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Murray, Utah, 84107, United States

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Richmond, Virginia, 23249, United States

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Novartis Investigative Site

Richmond, Virginia, 23298, United States

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Seattle, Washington, 98104, United States

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CABA, Buenos Aires, C1181ACH, Argentina

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Caba, Buenos Aires, C1280AEB, Argentina

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San Juan Bautista, Buenos Aires, C1073ABA, Argentina

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Edegem, Antwerpen, 2650, Belgium

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Leuven, 3000, Belgium

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Vancouver, British Columbia, V6Z 2K5, Canada

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Toronto, Ontario, M5G 2C4, Canada

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Toronto, Ontario, M6H 3MI, Canada

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Chicoutimi, Quebec, G7H 7K9, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Prague, 128 08, Czechia

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Shebeen El-Kom, Egypt

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Paris, 75651, France

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Pessac, 33604, France

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Strasbourg, 67098, France

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Mainz, 55131, Germany

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Würzburg, 97080, Germany

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New Delhi, National Capital Territory of Delhi, 110070, India

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Tel Aviv, 6423906, Israel

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Modena, Itlay, 41126, Italy

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Palermo, PA, 90127, Italy

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Roma, RM, 00168, Italy

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Verona, VR, 37126, Italy

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Milan, 20112, Italy

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Riga, LV-1006, Latvia

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Moscow, 101990, Russia

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Novartis Investigative Site

Moscow, 109544, Russia

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Singapore, 117549, Singapore

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Singapore, 169608, Singapore

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Santander, Cantabria, 39008, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Barcelona, Catalonia, 08036, Spain

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Valencia, Valencia, 46026, Spain

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Novartis Investigative Site

Pendik / Istanbul, Turkey, 34899, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35100, Turkey (Türkiye)

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Novartis Investigative Site

High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom

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Novartis Investigative Site

Aberdeen, AB25 2ZN, United Kingdom

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Novartis Investigative Site

Torquay, TQ2 7AA, United Kingdom

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Related Publications (2)

• 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.

  PMID: 31731005 RESULT

• 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.

  PMID: 33666272 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver; Liver Cirrhosis

Interventions

tropifexor; cenicriviroc

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 (862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: May 7, 2018
• Study Start: September 11, 2018
• Primary Completion: September 15, 2020
• Study Completion: October 15, 2020
• Last Updated: April 29, 2022
• Results First Posted: November 12, 2021

Record last verified: 2022-04

Locations

GB (3); IN (1); TU (2); RU (2); AR (3); US (27); DE (2); EG (1); FR (3); BE (2); SG (2); IL (1); LA (1); IT (5); CA (5); CZ (1); ES (4)