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Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin Compared to Each Monotherapy, in Adult Patients With NASH and Liver Fibrosis. (ELIVATE)

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ClinicalTrials.gov Identifier: NCT04065841
Recruitment Status : Not yet recruiting
First Posted : August 22, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Non Alcoholic Steatohepatitis (NASH) Drug: Tropifexor Drug: Licogliflozin Phase 2

Detailed Description:
Study to compare tropifexor and licogliflozin in combination to each monotherapy for efficacy, safety, and tolerability in patients with NASH and fibrosis (stage 2 or 3) as per NASH CRN histological score.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Oral Tropifexor (LJN452) & Licogliflozin (LIK066) Combination Therapy, Compared to Each Monotherapy, for Treatment of Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis.
Estimated Study Start Date : December 10, 2019
Estimated Primary Completion Date : May 12, 2020
Estimated Study Completion Date : April 12, 2022


Arm Intervention/treatment
Experimental: Arm A: combination therapy
tropifexor + licogliflozin
Drug: Tropifexor
Tropifexor is a highly potent, specific and orally available non-bile acid agonist of the bile acid receptor FXR.
Other Name: LJN452

Drug: Licogliflozin
Licogliflozin is a selective and potent inhibitor of the sodium glucose co-transporters (SGLTs) 1 and 2
Other Name: LIK066

Experimental: Arm B: tropifexor monotherapy
tropifexor (+ licogliflozin placebo)
Drug: Tropifexor
Tropifexor is a highly potent, specific and orally available non-bile acid agonist of the bile acid receptor FXR.
Other Name: LJN452

Experimental: Arm C: licogliflozin monotherapy
licogliflozin (+ tropifexor placebo)
Drug: Licogliflozin
Licogliflozin is a selective and potent inhibitor of the sodium glucose co-transporters (SGLTs) 1 and 2
Other Name: LIK066




Primary Outcome Measures :
  1. Proportion of patients with resolution of NASH and no worsening of fibrosis OR improvement in fibrosis by at least one stage without worsening of NASH at Week 48 compared with baseline. [ Time Frame: 48 weeks ]
    To demonstrate the efficacy of tropifexor + licogliflozin as assessed by histologic improvement after 48 weeks of combination treatment compared to each monotherapy treatment in patients with NASH and stage 2 or 3 fibrosis.


Secondary Outcome Measures :
  1. Proportion of patients who have at least one stage improvement in fibrosis without worsening of NASH at Week 48 compared with baseline [ Time Frame: 48 weeks ]
    Improvement in fibrosis by at least one stage with no worsening of NASH

  2. Proportion of patients with resolution of NASH and no worsening of fibrosis at Week 48 compared with baseline [ Time Frame: 48 weeks ]
    Resolution of NASH with no worsening of fibrosis after 48 weeks of treatment

  3. Proportion of patients who have at least one stage improvement in fibrosis at Week 48 compared with baseline [ Time Frame: 48 weeks ]
    Improvement in fibrosis by at least one stage

  4. Proportion of patients who have at least two stage improvement in fibrosis without worsening of NASH at Week 48 compared with baseline [ Time Frame: 48 weeks ]
    Improvement in fibrosis by at least two stages with no worsening of NASH

  5. Proportion of patients with 5% or more reduction in body weight at Week 48 compared to baseline [ Time Frame: 48 weeks ]
    Reduction in body weight from baseline

  6. Change in liver fat content based on MRI - PDFF (in 60% of patients) over time up to Week 48 compared with baseline [ Time Frame: 48 weeks ]
    Change in liver fat content

  7. Change in ALT and AST over time up to Week 48 compared with baseline [ Time Frame: 48 weeks ]
    To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH (ALT and AST)

  8. Change in GGT over time up to Week 48 compared with baseline [ Time Frame: 48 weeks ]
    To determine the relationship of investigational treatment and GGT, a marker of cholestasis and oxidative stress

  9. Number of participants with adverse events [ Time Frame: 48 weeks ]
    To evaluate the safety and tolerability of tropifexor (LJN452) in combination with licogliflozin (LIK066), compared to monotherapy of each compound from baseline



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

• Presence of NASH as demonstrated by the following: NASH with fibrosis stage 2 or 3 confirmed by central reader's evaluation using NAFLD Activity Score (NAS) and NASH CRN criteria, of liver biopsy obtained no more than 6 months before randomization.

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Uncontrolled type 2 diabetes defined as glycated hemoglobin (HbA1c) ≥ 9.5% 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:

    • Abnormal platelet count
    • Serum albumin < 3.2g/dL
    • International Normalized Radio (INR) > 1.3
    • ALT or AST > 5xULN
    • Total bilirubin >1.3 mg/dL (22 µmol/L) (including Gilbert's syndrome)
    • Alkaline phosphatase > 300 IU/L
    • History of esophageal varices, ascites or hepatic encephalopathy
    • Splenomegaly

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04065841


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04065841     History of Changes
Other Study ID Numbers: CLJN452D12201C
First Posted: August 22, 2019    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
NASH
Non alcoholic steatohepatitis
Tropifexor (LJN452)
Licogliflozin (LIK066)
Additional relevant MeSH terms:
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Fatty Liver
Liver Cirrhosis
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases