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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)

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ClinicalTrials.gov Identifier: NCT04065841
Recruitment Status : Recruiting
First Posted : August 22, 2019
Last Update Posted : October 20, 2020
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 and each monotherapy, compared with placebo 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 Other: Placebo Phase 2

Detailed Description:
Study to compare tropifexor and licogliflozin in combination and each monotherapy with placebo 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 : 380 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 and Each Monotherapy, Compared With Placebo for Treatment of Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis.(ELIVATE)
Actual Study Start Date : December 30, 2019
Estimated Primary Completion Date : March 15, 2022
Estimated Study Completion Date : April 12, 2022

Resource links provided by the National Library of Medicine


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

Placebo Comparator: Arm D: Placebo
licogliflozin placebo + tropifexor placebo
Other: Placebo
licogliflozin placebo + tropifexor placebo




Primary Outcome Measures :
  1. Whether the participant achieves at least one stage of improvement in fibrosis without worsening of NASH (no worsening of hepatocellular ballooning or lobular inflammation) (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate the efficacy of tropifexor + licogliflozin in combination therapy and each monotherapy treatment, as assessed by histologic improvement compared to placebo in participants with NASH and stage 2 or 3 fibrosis.

  2. Whether the participant has resolution of NASH without worsening of fibrosis (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate improvement in fibrosis by at least one stage


Secondary Outcome Measures :
  1. Whether the participant achieves resolution of NASH and no worsening of fibrosis OR improvement in fibrosis by at least one stage without worsening of NASH (no worsening of hepatocellular ballooning or lobular inflammation) (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate the efficacy of combination therapy and two monotherapies in NASH or fibrosis with a composite endpoint.

  2. Whether the participant has at least one stage improvement in fibrosis (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate the efficacy of combination therapy and two monotherapies in NASH or fibrosis with a composite endpoint.

  3. Whether the participant has at least two stage improvement in fibrosis without worsening of NASH (no worsening of hepatocellular ballooning or lobular inflammation) (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate improvement in fibrosis by at least two stages with no worsening of NASH

  4. Whether the participant has 5% or more reduction in body weight (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate reduction in body weight

  5. Change in liver fat content based on MRI - PDFF (in 40% of participants) [ Time Frame: 48 weeks ]
    To evaluate change in liver fat content

  6. Change in ALT and AST over time [ Time Frame: 48 weeks ]
    To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH (ALT and AST)

  7. Change in GGT over time [ Time Frame: 48 weeks ]
    To evaluate the relationship of investigational treatment and GGT, a marker of cholestasis and oxidative stress

  8. Occurrence of adverse events, serious adverse events, adverse events resulting in discontinuation of study treatment, adverse events of special interest and changes in vital signs and laboratory parameters [ Time Frame: 48 weeks ]
    To evaluate the safety and tolerability of tropifexor (LJN452) in combination with licogliflozin (LIK066), and each monotherapy treatment, compared to placebo



Information from the National Library of Medicine

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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 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

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

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04065841    
Other Study ID Numbers: CLJN452D12201C
First Posted: August 22, 2019    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: October 2020
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)
Placebo
Additional relevant MeSH terms:
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Fatty Liver
Liver Cirrhosis
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases