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)

Novartis

Status and phase: Terminated; Phase 2

Conditions: Non Alcoholic Steatohepatitis (NASH)

Treatments: Drug: Tropifexor; Other: Placebo; Drug: Licogliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04065841

CLJN452D12201C

2019-002324-32 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

The study consisted of 1) a screening period, 2) a treatment period starting from randomization on Day 0 and running to Week 48, and 3) a follow-up period of 4 weeks after the last dose of study treatment. The study duration from first dose of study medication was 52 weeks.

Enrollment: 234 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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234 participants in 4 patient groups, including a placebo group

Arm A: combination therapy

Experimental group

Description:

Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally

Treatment:

Drug: Licogliflozin

Drug: Tropifexor

Arm B: tropifexor monotherapy

Experimental group

Description:

Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally

Treatment:

Drug: Tropifexor

Arm C: licogliflozin monotherapy

Experimental group

Description:

Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally

Treatment:

Drug: Licogliflozin

Arm D: Placebo

Placebo Comparator group

Description:

Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily

Treatment:

Other: Placebo