- ICH GCP
- US Clinical Trials Registry
- 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. (ELIVATE)
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Buenos Aires
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Florencio Varela, Buenos Aires, Argentina, C1073ABA
- Novartis Investigative Site
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Mechelen, Belgium, 2800
- Novartis Investigative Site
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BA
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Salvador, BA, Brazil, 40110-160
- Novartis Investigative Site
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RS
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Porto Alegre, RS, Brazil, 90035-003
- Novartis Investigative Site
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SP
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Sao Paulo, SP, Brazil, 04037-002
- Novartis Investigative Site
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São Paulo, SP, Brazil, 05403-000
- Novartis Investigative Site
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Sofia, Bulgaria, 1413
- Novartis Investigative Site
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Sofia, Bulgaria, 1784
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada, H4A 3J1
- Novartis Investigative Site
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Los Rios
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Valdivia, Los Rios, Chile, 5110683
- Novartis Investigative Site
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Valparaiso
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Vina del Mar, Valparaiso, Chile, 2540364
- Novartis Investigative Site
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Bogota, Colombia, 110131
- Novartis Investigative Site
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Antioquia
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Medellin, Antioquia, Colombia, 050001
- Novartis Investigative Site
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Rionegro, Antioquia, Colombia, 054047
- Novartis Investigative Site
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Aarhus, Denmark, 8000 C
- Novartis Investigative Site
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Tallinn, Estonia, 10617
- Novartis Investigative Site
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Berlin, Germany, 10825
- Novartis Investigative Site
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Dresden, Germany, 01307
- Novartis Investigative Site
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Essen, Germany, 45147
- Novartis Investigative Site
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Mainz, Germany, 55131
- Novartis Investigative Site
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Delhi
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New Delhi, Delhi, India, 110070
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20112
- Novartis Investigative Site
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Rozzano, MI, Italy, 20089
- Novartis Investigative Site
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PA
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Palermo, PA, Italy, 90127
- Novartis Investigative Site
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PD
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Padova, PD, Italy, 35128
- Novartis Investigative Site
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Kagawa
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Takamatsu city, Kagawa, Japan, 760 8557
- Novartis Investigative Site
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Kanagawa
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Yokohama-city, Kanagawa, Japan, 236-0004
- Novartis Investigative Site
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Saga
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Saga-city, Saga, Japan, 849-8501
- Novartis Investigative Site
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Shimane
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Izumo-city, Shimane, Japan, 693 8501
- Novartis Investigative Site
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Seoul, Korea, Republic of, 03080
- Novartis Investigative Site
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Seoul
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Dongjak Gu, Seoul, Korea, Republic of, 07061
- Novartis Investigative Site
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Mexico, Mexico, 22381
- Novartis Investigative Site
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Ciudad De Mexico
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Cuauhtemoc, Ciudad De Mexico, Mexico, 06700
- Novartis Investigative Site
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Jalisco
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Guadalajara, Jalisco, Mexico, 44130
- Novartis Investigative Site
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Nuevo Leon
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Monterrey, Nuevo Leon, Mexico, 64460
- Novartis Investigative Site
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San Juan, Puerto Rico, 00927
- Novartis Investigative Site
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Novosibirsk, Russian Federation, 630090
- Novartis Investigative Site
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Samara, Russian Federation, 443063
- Novartis Investigative Site
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St Petersburg, Russian Federation, 199226
- Novartis Investigative Site
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St Petersburg, Russian Federation, 199034
- Novartis Investigative Site
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Singapore, Singapore, 119074
- Novartis Investigative Site
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Singapore, Singapore, 169608
- Novartis Investigative Site
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Cape Town, South Africa, 7531
- Novartis Investigative Site
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Eastern Cape
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Port Elizabeth, Eastern Cape, South Africa, 6001
- Novartis Investigative Site
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Madrid, Spain, 28046
- Novartis Investigative Site
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Madrid, Spain, 28009
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Kaohsiung, Taiwan, 80756
- Novartis Investigative Site
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Tainan, Taiwan, 70403
- Novartis Investigative Site
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Topkapı
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Istanbul, Topkapı, Turkey, 34010
- Novartis Investigative Site
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Aberdeen, United Kingdom, AB25 2ZN
- Novartis Investigative Site
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London, United Kingdom, SE5 9RS
- Novartis Investigative Site
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Alabama
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Dothan, Alabama, United States, 36305
- Novartis Investigative Site
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California
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Coronado, California, United States, 92118
- Novartis Investigative Site
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Los Angeles, California, United States, 90057
- Novartis Investigative Site
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Pasadena, California, United States, 91105
- Novartis Investigative Site
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San Diego, California, United States, 92123
- Novartis Investigative Site
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Van Nuys, California, United States, 91405
- Novartis Investigative Site
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Ventura, California, United States, 93003
- Novartis Investigative Site
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Florida
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Doral, Florida, United States, 33166
- Novartis Investigative Site
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Lehigh Acres, Florida, United States, 33936
- Novartis Investigative Site
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Miami, Florida, United States, 33165-7574
- Novartis Investigative Site
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Indiana
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South Bend, Indiana, United States, 46635
- Novartis Investigative Site
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Mississippi
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Jackson, Mississippi, United States, 39216
- Novartis Investigative Site
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Missouri
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Chesterfield, Missouri, United States, 63005
- Novartis Investigative Site
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New Mexico
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Albuquerque, New Mexico, United States, 87109
- Novartis Investigative Site
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New York
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Manhasset, New York, United States, 11030
- Novartis Investigative Site
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North Carolina
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Lenoir, North Carolina, United States, 28645
- Novartis Investigative Site
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Morehead City, North Carolina, United States, 28557
- Novartis Investigative Site
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Oklahoma
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Tulsa, Oklahoma, United States, 74104
- Novartis Investigative Site
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South Carolina
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Greenville, South Carolina, United States, 29605
- Novartis Investigative Site
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Greenwood, South Carolina, United States, 29646
- Novartis Investigative Site
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Summerville, South Carolina, United States, 29485
- Novartis Investigative Site
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Tennessee
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Hermitage, Tennessee, United States, 37076
- Novartis Investigative Site
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Texas
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Arlington, Texas, United States, 76012
- Novartis Investigative Site
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Dallas, Texas, United States, 75230
- Novartis Investigative Site
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San Antonio, Texas, United States, 78229
- Novartis Investigative Site
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San Antonio, Texas, United States, 78240
- Novartis Investigative Site
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San Antonio, Texas, United States, 78215
- Novartis Investigative Site
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Sugar Land, Texas, United States, 77479
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
- NASH using NAFLD Activity Score (NAS) ≥ 4 with at least 1 point each in inflammation and ballooning and
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm A: combination therapy
Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally
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100mcg+30mcg+10mcg capsules of tropifexor taken orally every day until the 140 mcg capsule of tropifexor taken orally every day is produced, then patients will switch to the single 140mcg capsule taken orally every day
Other Names:
30mg tablet of licoglifozin taken orally every day
Other Names:
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Experimental: Arm B: tropifexor monotherapy
Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally
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100mcg+30mcg+10mcg capsules of tropifexor taken orally every day until the 140 mcg capsule of tropifexor taken orally every day is produced, then patients will switch to the single 140mcg capsule taken orally every day
Other Names:
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Experimental: Arm C: licogliflozin monotherapy
Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally
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30mg tablet of licoglifozin taken orally every day
Other Names:
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Placebo Comparator: Arm D: Placebo
Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
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licogliflozin placebo + tropifexor placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Histological Improvement: Number and Percentage of Participants Who Responded at Week 48 Compared With Baseline
Time Frame: Baseline, Week 48
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Response was defined as at least a one-stage improvement in fibrosis without worsening of nonalcoholic steatohepatitis (NASH) Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis. |
Baseline, Week 48
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Number and Percentage of Participants With Resolution of NASH and no Worsening of Fibrosis
Time Frame: 48 weeks
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Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader.
NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
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48 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
Time Frame: 48 weeks
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Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader.
NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
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48 weeks
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Number and Percentage of Participants With at Least One Stage Improvement in Fibrosis
Time Frame: 48 weeks
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Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader.
NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
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48 weeks
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Number and Percentage of Participants With at Least Two Stage Improvement in Fibrosis Without Worsening of NASH
Time Frame: 48 weeks
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Fibrosis staging and Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader.
NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
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48 weeks
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Number and Percentage of Participants Achieving 5% or More Reduction in Body Weight at Week 48 Compared With Baseline
Time Frame: Baseline, Week 48
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Whether the participants had 5% or more reduction in body weight.
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Baseline, Week 48
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Change From Baseline to Week 48 in Percent Liver Fat Content Based on Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI - PDFF)
Time Frame: Baseline, Week 48
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Change in liver fat content based on MRI-PDFF.
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Baseline, Week 48
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Change From Baseline in Alanine Transaminase (ALT) Over Time
Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.
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Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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Change From Baseline in Aspartate Aminotransferase (AST) Over Time
Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.
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Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time
Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.
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Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLJN452D12201C
- 2019-002324-32 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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