A Study to Assess ARI-3037MO on Hepatic Fat Metabolism in Patients With Dysglycemia and Evidence of Hepatic Steatosis

Nonalcoholic Steatohepatitis Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02574325
• Other study ID #: ARI-3037MO-006
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 8, 2015
• Last updated: August 5, 2016
• Start date: October 2015
• Est. completion date: December 2016

Study information

• Verified date: October 2015
• Source: Arisaph Pharmaceuticals Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary objective To investigate the effect of a 24-week, twice daily dosing regimen of ARI-3037MO compared to placebo on plasma triglyceride (TG) levels, liver enzymes and hepatic fat content in patients with dysglycemia and hepatic steatosis due to nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Secondary Objective To investigate the safety and tolerability of a 24-week, twice daily dosing regimen of ARI-3037MO compared to placebo in patients with dysglycemia and evidence of NAFLD or NASH.

Description:

This randomized,double-blind, placebo-controlled study will enroll 36 men and women with a diagnosis of NAFLD orNASH. The study will be conducted over a period of approximately 28 wks and will include:a Screening Phase (Days -14to -1); a 24-week long Treatment Phase, during which patients will be randomly assigned to receive ARI-3037MO or placebo; an End-of-study Visit (ESV) scheduled 2 wks after the end of the Treatment Phase The Screening Phase will include 2 visits. Visit 1:There will be an initial assessment of a patient's eligibility for participation in the study. A complete medical history will be obtained and prospective study patients will undergo physical examinations and laboratory evaluations. For patients who have had a liver biopsy in the 6months prior to Visit 1, the histology findings, i.e., NAS, steatosis score and fibrosis score will be recorded. Visit 2:Approximately 1 week after Visit 1, and after the results of clinical laboratory screening test results have been reviewed by the Principal Investigator (PI), patients will be contacted to advise them of their eligibility to continue in the study. Eligible patients will undergo liver magnetic resonance imaging (MRI) to assess intrahepatic fat content. Treatment Phase Patients with MRI results showing intrahepatic fat content of ≥10% will be entered into the Treatment Phase of the study. The Treatment Phase will include 4 outpatient visits over a period of 24 weeks. Visit 3:Patients will be randomly assigned to receive ARI-3037MO or placebo on Day 1 of a 24-week long outpatient treatment period. Baseline assessments, including FibroTest®, FibroScan® and clinical laboratory tests, will be performed, and patients will take study drug twice daily. Visits 4, 5 and 6: During the Treatment Phase, patients will visit the study clinic at 4, 12 and 24 weeks (± 4 days) after Day 1 for evaluations and examinations and to collect study drug. Twenty-four weeks after the start of dosing, at the end of the Treatment Phase, patients will undergo a follow-up MRI and FibroScan† to assess change from baseline in intrahepatic fat content and liver fibrosis, respectively.

†If FibroScan equipment is available at the study site End-of-Study Visit Visit 7:An ESV will occur 2 weeks (± 4 days) after the end of the Treatment Phase.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: December 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male and female patients = 18 years of age at study entry

2. Female patients must be of nonchildbearing potential

3. Have a stable diet and agree to maintain this diet throughout the study

4. Have not gained or lost = 10 lbs (4.5 kg) of body weight within 6months prior to Screening Visit 1

5. Have a body mass index (BMI) between 28 and 45 kg.m-2, inclusive

6. Have elevated alanine aminotransferase (ALT) levels. For men: 50 IU/L to 250 IU/L, inclusive. For women: 40 IU/L to 240 IU/L, inclusive.

7. Have HbA1c of < 9.5

8. Have a intrahepatic fat content of = 10% confirmed by liver MRI

9. If taking antidiabetic therapies (excluding thiazolidines as per exclusion Criterion No. 13), i.e., metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, insulin; must be on a stable dose for at least 3months prior to Screening Visit 1. Similarly, if taking lipid lowering therapies; must be on a stable dose for at least 3 months prior to Screening Visit 1.

10. Understands the study requirements and the treatment procedures, is willing to comply with all protocol-required evaluations and provides written informed consent before any study specific tests or procedures are performed

Exclusion Criteria:

1. A history of hepatic disease such as chronic hepatitis C virus or concurrent active hepatitis B virus (i.e., serum positive for hepatitis B surface antigen)

2. Autoimmune hepatitis

3. Primary biliary cirrhosis

4. Sclerosing cholangitis

5. Hereditary hemochromatosis

6. History of chronic / repeat blood transfusion (i.e., = 20 units of blood)

7. Alpha-1 anti-trypsin deficiency

8. Wilson's disease

9. Thyroid disease

10. Bariatric surgery within 5 years prior to Screening Visit 1

11. Hepatic disease due to substance abuse

12. Have any concurrent disease or condition not listed above that, in the opinion of the PI, would make the patient unsuitable for participation in the study

13. Currently taking thiazolidines (glitazone therapy, i.e., Rosiglitazone, Pioglitazone)

14. Liver biopsy in the past 90 days with negative results for cirrhosis and steatosis

15. No evidence of hepatic decompensation or elevated serum bilirubin > 1.5 times the upper limit of normal

16. Estimated glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease equation

17. Known substance abuse

18. Current smoker or a history of smoking (> 10 cigarettes, > 3 cigars or > 3 pipes/day)

19. Current consumption of > 3 units of alcohol per day (> 21 units per week) for men and > 2 units of alcohol per day (> 14 units per week) for women

20. Currently participating in another clinical study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Placebo
Control
• ARI-3037MO
Treatment

Locations

Country	Name	City	State
United States	Gastroenterology & Hepatology CRU, St Louis University	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Arisaph Pharmaceuticals Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy as measured by change in intra hepatic fat content	Change in intra hepatic fat content by MRI	24 wks	No
Primary	Efficacy as measured by change in plasma ALT levels	Change in plasma ALT levels from baseline	24 wks	No
Primary	Efficacy as measured by change in plasma TG levels	Change in plasma TG levels from baseline	24 wks	No
Secondary	Safety as measured by the occurrence of flushing (number of episodes) and itching (number of episodes)	Occurrence of cutaneous symptoms	24 wks	Yes
Secondary	Safety as measured by effect of ARI-3037MO on on glycemic control	Change in HbA1c levels from baseline	24 wks	Yes
Secondary	Safety as measured by effect of ARI-3037MO on serum bilirubin, alkaline phosphatase, Prothrombin time and plasma albumin levels	Change of liver function tests from baseline	24 wks	Yes
Secondary	Safety as measured by effect of ARI-3037MO on gastrointestinal systems; episodes of nausea, vomiting and diarrhea	occurrence of GI symptoms	24 wks	Yes