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Trial record 1 of 1 for:    CLjN452D12201C
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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 )

Tracking Information
First Submitted Date  ICMJE August 19, 2019
First Posted Date  ICMJE August 22, 2019
Last Update Posted Date October 20, 2020
Actual Study Start Date  ICMJE December 30, 2019
Estimated Primary Completion Date March 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • 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.
  • 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.
  • 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
  • Whether the participant has 5% or more reduction in body weight (YES/NO) [ Time Frame: 48 weeks ]
    To evaluate reduction in body weight
  • Change in liver fat content based on MRI - PDFF (in 40% of participants) [ Time Frame: 48 weeks ]
    To evaluate change in liver fat content
  • 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)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non Alcoholic Steatohepatitis (NASH)
Intervention  ICMJE
  • 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
  • Other: Placebo
    licogliflozin placebo + tropifexor placebo
Study Arms  ICMJE
  • Experimental: Arm A: combination therapy
    tropifexor + licogliflozin
    Interventions:
    • Drug: Tropifexor
    • Drug: Licogliflozin
  • Experimental: Arm B: tropifexor monotherapy
    tropifexor (+ licogliflozin placebo)
    Intervention: Drug: Tropifexor
  • Experimental: Arm C: licogliflozin monotherapy
    licogliflozin (+ tropifexor placebo)
    Intervention: Drug: Licogliflozin
  • Placebo Comparator: Arm D: Placebo
    licogliflozin placebo + tropifexor placebo
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 16, 2020)
380
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2019)
210
Estimated Study Completion Date  ICMJE April 12, 2022
Estimated Primary Completion Date March 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Belgium,   Bulgaria,   Canada,   Chile,   Colombia,   Estonia,   Germany,   India,   Italy,   Japan,   Korea, Republic of,   Russian Federation,   Singapore,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04065841
Other Study ID Numbers  ICMJE CLJN452D12201C
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP