Study to assess efficacy, safety, and tolerability of oral tropifexor (LJN452) & licogliflozin (LIK066) combination therapy, and each monotherapy, compared with placebo (ELIVATE)
- Conditions
- nonalcoholic steatohepatitis
- Registration Number
- JPRN-jRCT2080225078
- Lead Sponsor
- ovartis Pharma. K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- terminated
- Sex
- All
- Target Recruitment
- 380
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
- Type 1 diabetes mellitus
- Uncontrolled type 2 diavetes defined as blycated 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 > 5xULN(confirmed by 2 values during screening).
- Total billirubin > 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 & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>- Whether the participant achieves at least one stage of improvement in fibrosis without worsening of NASH (YES/NO) [ Time Frame: 48 weeks ] <br>- Whether the participant has resolution of NASH without worsening of fibrosis (YES/NO) [ Time Frame: 48 weeks ]
- Secondary Outcome Measures
Name Time Method efficacy<br>- 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 (YES/NO) [ Time Frame: 48 weeks ]<br>- Whether the participant has at least one stage improvement in fibrosis (YES/NO) [ Time Frame: 48 weeks ]<br>- Whether the participant has at least two stage improvement in fibrosis without worsening of NASH (YES/NO) [ Time Frame: 48 weeks ]<br>- Whether the participant has 5% or more reduction in body weight (YES/NO) [ Time Frame: 48 weeks ]<br>- Change in liver fat content based on MRI - PDFF (in 40% of participants) [ Time Frame: 48 weeks ]<br>- Change in ALT and AST over time [ Time Frame: 48 weeks ]<br>- Change in GGT over time [ Time Frame: 48 weeks ]<br>- 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 ]