Clinical trial NCT04065841: Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis.
Official title: A Randomized, Double-blind, Parallel-group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Oral Tropifexor (LJN452) & Licogliflozin (LIK066) Combination Therapy and Each Monotherapy, Compared With Placebo for Treatment of Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis.(ELIVATE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non Alcoholic Steatohepatitis (NASH)
Keywords: NASH
Non alcoholic steatohepatitis
Tropifexor
LJN452
Licogliflozin
LIK066
Placebo
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-08-22
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Randomized, double-blind, parallel-group, multicenter study to assess efficacy, safety, and tolerability of oral tropifexor \& licogliflozin combination therapy and each monotherapy, compared with placebo for treatment of adult patients with nonalcoholic steatohepatitis (NASH) and liver fibrosis.

Detailed description: The study consisted of 1) a screening period, 2) a treatment period starting from randomization on Day 0 and running to Week 48, and 3) a follow-up period of 4 weeks after the last dose of study treatment. The study duration from first dose of study medication was 52 weeks.

Eligibility criteria: Inclusion Criteria:

Presence of NASH with fibrosis confirmed by central reader's evaluation of liver biopsy obtained no more than 6 months before randomization as demonstrated by the following:

1. NASH using NAFLD Activity Score (NAS) ≥ 4 with at least 1 point each in inflammation and ballooning and
2. Fibrosis stage 2 or 3 using NASH CRN fibrosis criteria

Exclusion Criteria:

* Type 1 diabetes mellitus
* Uncontrolled type 2 diabetes defined as glycated hemoglobin (HbA1c) ≥ 9.0% at screening
* HbA1c \< 6.5% at screening in Type 2 diabetics currently treated with insulin or sulfonylureas
* Clinical evidence of liver impairment as defined by the presence of any of the following abnormalities:

  * Platelet count \< LLN (see Central laboratory manual).
  * Serum albumin \< LLN (see Central laboratory manual).
  * International Normalized Ratio (INR) \> ULN (see Central laboratory manual).
  * ALT or AST \> 5× ULN (confirmed by 2 values during screening).
  * Total bilirubin \> ULN (see Central laboratory manual) (confirmed by 2 values during screening), including Gilbert's syndrome.
  * Alkaline phosphatase \> 300 IU/L (confirmed by 2 values during screening).
  * History of esophageal varices, ascites or hepatic encephalopathy
  * Splenomegaly
  * MELD score \>12

Primary outcomes:
measure: Histological Improvement: Number and Percentage of Participants Who Responded at Week 48 Compared With Baseline
timeFrame: Baseline, Week 48
measure: Number and Percentage of Participants With Resolution of NASH and no Worsening of Fibrosis
timeFrame: 48 weeks
Secondary outcomes:
measure: Number and Percentage of Participants Who Achieved Resolution of NASH and no Worsening of Fibrosis OR Improvement in Fibrosis by at Least One Stage Without Worsening of NASH
timeFrame: 48 weeks
measure: Number and Percentage of Participants With at Least One Stage Improvement in Fibrosis
timeFrame: 48 weeks
measure: Number and Percentage of Participants With at Least Two Stage Improvement in Fibrosis Without Worsening of NASH
timeFrame: 48 weeks
measure: Number and Percentage of Participants Achieving 5% or More Reduction in Body Weight at Week 48 Compared With Baseline
timeFrame: Baseline, Week 48
measure: Change From Baseline to Week 48 in Percent Liver Fat Content Based on Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI - PDFF)
timeFrame: Baseline, Week 48
measure: Change From Baseline in Alanine Transaminase (ALT) Over Time
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
measure: Change From Baseline in Aspartate Aminotransferase (AST) Over Time
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
measure: Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Gut PC Digestive Health Specialist
state: Alabama
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Los Angeles
country: United States
facility: Velocity Clinical Trials
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: Van Nuys
country: United States
facility: San fernando Valley Health Institute
state: California
city: Ventura
country: United States
facility: Island View Gastroenterology Associates
state: California
city: Doral
country: United States
facility: Integrity Clinical Rsh LLC
state: Florida
city: Lehigh Acres
country: United States
facility: Galenus Group
state: Florida
city: Miami
country: United States
facility: Genoma Research Group Inc
state: Florida
city: South Bend
country: United States
facility: Digestive Res Alliance of Michiana
state: Indiana
city: Jackson
country: United States
facility: Southern Therapy and Adv Res LLC
state: Mississippi
city: Chesterfield
country: United States
facility: Clinical Research Professionals Inc
state: Missouri
city: Albuquerque
country: United States
facility: Southwest Gastroenterology Associates
state: New Mexico
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Lenoir
country: United States
facility: Clinical Trials Of America LLC
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes And Endocrinology Conslt
state: North Carolina
city: Tulsa
country: United States
facility: Options Health Research
state: Oklahoma
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Greenwood
country: United States
facility: Digestive Disease Research
state: South Carolina
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Hermitage
country: United States
facility: Summit Medical Care
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes and Endocrine Center
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Florencio Varela
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mechelen
country: Belgium
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Valdivia
country: Chile
facility: Novartis Investigative Site
state: Los Rios
city: Vina del Mar
country: Chile
facility: Novartis Investigative Site
state: Valparaiso
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Rionegro
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Aarhus N
country: Denmark
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Takamatsu city
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Saga-city
country: Japan
facility: Novartis Investigative Site
state: Saga
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Dongjak Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Cuauhtemoc
country: Mexico
facility: Novartis Investigative Site
state: Ciudad De Mexico
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Mexico
country: Mexico
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
city: Novosibirsk
country: Russian Federation
facility: Novartis Investigative Site
city: Samara
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Port Elizabeth
country: South Africa
facility: Novartis Investigative Site
state: Eastern Cape
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: Topkapi
city: Aberdeen
country: United Kingdom
facility: Novartis Investigative Site
state: Grampian Region
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: