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

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

— TANDEM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03517540
• Other study ID #: CLJC242A2201J
• Secondary ID: 2017-004208-24LJ
• Status: Completed
• Phase: Phase 2
• Start date: September 11, 2018
• Est. completion date: October 15, 2020

Study information

• Verified date: April 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 193
• Est. completion date: October 15, 2020
• Est. primary completion date: September 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• Tropifexor (LJN452)
Comparison with monotherapy and different combination doses
• Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Florencio Varela	Buenos Aires
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Chicoutimi	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Czechia	Novartis Investigative Site	Prague
Egypt	Novartis Investigative Site	Shebeen El-Kom
France	Novartis Investigative Site	Paris Cedex 13
France	Novartis Investigative Site	Pessac Cedex
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Wuerzburg
India	Novartis Investigative Site	New Delhi	Delhi
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Milan
Italy	Novartis Investigative Site	Modena	Itlay
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Verona	VR
Latvia	Novartis Investigative Site	Riga
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Pendik / Istanbul
United Kingdom	Novartis Investigative Site	Aberdeen
United Kingdom	Novartis Investigative Site	High Heaton	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Torquay
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Chandler	Arizona
United States	Novartis Investigative Site	Chattanooga	Tennessee
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Concord	North Carolina
United States	Novartis Investigative Site	Coronado	California
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Germantown	Tennessee
United States	Novartis Investigative Site	Hermitage	Tennessee
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	Metairie	Louisiana
United States	Novartis Investigative Site	Morehead City	North Carolina
United States	Novartis Investigative Site	Murray	Utah
United States	Novartis Investigative Site	North Little Rock	Arkansas
United States	Novartis Investigative Site	Pasadena	California
United States	Novartis Investigative Site	Providence	Rhode Island
United States	Novartis Investigative Site	Rialto	California
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Shreveport	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Allergan

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Czechia,  Egypt,  France,  Germany,  India,  Israel,  Italy,  Latvia,  Russian Federation,  Singapore,  Spain,  Turkey,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of Participants Who Have at Least a One Point Improvement in Fibrosis	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
Secondary	Proportion of Participants With Resolution of Steatohepatitis	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

External Links

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