Clinical trial NCT03517540: Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-alcoholic Steatohepatitis (NASH)
Keywords: Steatohepatitis
NASH
NAFLD
Fatty Liver Disease
Liver
Liver fibrosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Allergan
First posted: 2018-05-07
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 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:
measure: Proportion of Participants Who Have at Least a One Point Improvement in Fibrosis
timeFrame: baseline to 48 Weeks
measure: Proportion of Participants With Resolution of Steatohepatitis
timeFrame: baseline to 48 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Novartis Investigative Site
state: Arizona
city: North Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Coronado
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Pasadena
country: United States
facility: Novartis Investigative Site
state: California
city: Rialto
country: United States
facility: Novartis Investigative Site
state: California
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Metairie
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Shreveport
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Concord
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Durham
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Morehead City
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Providence
country: United States
facility: Novartis Investigative Site
state: Rhode Island
city: Chattanooga
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Germantown
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Hermitage
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Murray
country: United States
facility: Novartis Investigative Site
state: Utah
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Florencio Varela
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Prague
country: Czechia
facility: Novartis Investigative Site
city: Shebeen El-Kom
country: Egypt
facility: Novartis Investigative Site
city: Paris Cedex 13
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Modena
country: Italy
facility: Novartis Investigative Site
state: Itlay
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Milan
country: Italy
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Pendik / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: High Heaton
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle Upon Tyne
city: Aberdeen
country: United Kingdom
facility: Novartis Investigative Site
city: Torquay
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.