Volixibat in the treatment of adults with Nonalcoholic Steatohepatitis (NASH)

Phase 1

• Conditions: Nonalcoholic steatohepatitis (NASH), is a clinical condition occurring in individuals who do not drink excessive alcohol (>20 grams/day), yet have hepatic histology which is indistinguishable from that seen with alcoholic excess. NASH has a 20% likelihood of progression to advanced disease including fibrosis, cirrhosis and its complications including liver failure and the need for a liver transplant (Angulo et al., 2002).; MedDRA version: 20.0 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2016-000203-82-GB
• Lead Sponsor: Shire Human Genetic Therapies, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-05-27
• Study Completion: 2018-07-27
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 197

Inclusion Criteria

1. Age 18-80 years inclusive.
2. Males and females
3. Presence of = 5% steatosis on screening MRI from a centrally read radiologist performed either during the Screening period or within 6 months prior to the first visit.
4. Histologic confirmation of NASH without cirrhosis (F0-F3) from a centrally read liver biopsy performed either during the Screening period or within 6 months prior to the first visit with a NAS of = 4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Presence of or history of cirrhosis or evidence of decompensated liver disease (ie, ascites, variceal bleeding, etc.) or hepatocellular carcinoma.
2. History or presence of other concomitant liver disease as assessed by the investigator or determined by laboratory findings
3. Weight change = 5% after qualifying liver biopsy performed.
4. Treatment with Vitamin E, thiazolidinediones, or glucagon-like peptide-1 receptors agonists (GLP1 RA) unless subject on a stable dose for 6 months prior to qualifying liver biopsy and not initiated after qualifying liver biopsy and will continue the same dosing regimen throughout study participation
5. Uncontrolled diabetes defined as HbA1c of = 9.5% within 60 days prior to enrollment.
6. Serum AST > 7 times upper limit of normal (ULN) at Screening.
7. Serum ALT > 7 times ULN at Screening.
8. Elevated serum creatinine = 2.0 mg/dL.
9. International normalized ratio (INR) >1.3
10. TB = 2.0 x ULN at Screening (Except for documented Gilbert’s syndrome]
11. Platelet count < 130 × 10E9/L
12. Uncontrolled thyroid disease.
13. Type 1 diabetes mellitus.
14. Known history of alcohol or other substance abuse within the last year or at any time during the study based on investigator’s discretion

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified