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

Primary Purpose

Nonalcoholic Steatohepatitis

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo

ARI-3037MO

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female patients ≥ 18 years of age at study entry
Female patients must be of nonchildbearing potential
Have a stable diet and agree to maintain this diet throughout the study
Have not gained or lost ≥ 10 lbs (4.5 kg) of body weight within 6months prior to Screening Visit 1
Have a body mass index (BMI) between 28 and 45 kg.m-2, inclusive
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.
Have HbA1c of < 9.5
Have a intrahepatic fat content of ≥ 10% confirmed by liver MRI
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.
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:

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)
Autoimmune hepatitis
Primary biliary cirrhosis
Sclerosing cholangitis
Hereditary hemochromatosis
History of chronic / repeat blood transfusion (i.e., ≥ 20 units of blood)
Alpha-1 anti-trypsin deficiency
Wilson's disease
Thyroid disease
Bariatric surgery within 5 years prior to Screening Visit 1
Hepatic disease due to substance abuse
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
Currently taking thiazolidines (glitazone therapy, i.e., Rosiglitazone, Pioglitazone)
Liver biopsy in the past 90 days with negative results for cirrhosis and steatosis
No evidence of hepatic decompensation or elevated serum bilirubin > 1.5 times the upper limit of normal
Estimated glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease equation
Known substance abuse
Current smoker or a history of smoking (> 10 cigarettes, > 3 cigars or > 3 pipes/day)
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
Currently participating in another clinical study

Sites / Locations

Gastroenterology & Hepatology CRU, St Louis University

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

ARI-3037MO

Arm Description

Placebo

ARI-3037MO

Outcomes

Primary Outcome Measures

Efficacy as measured by change in intra hepatic fat content

Change in intra hepatic fat content by MRI

Efficacy as measured by change in plasma ALT levels

Change in plasma ALT levels from baseline

Efficacy as measured by change in plasma TG levels

Change in plasma TG levels from baseline

Secondary Outcome Measures

Safety as measured by the occurrence of flushing (number of episodes) and itching (number of episodes)

Occurrence of cutaneous symptoms

Safety as measured by effect of ARI-3037MO on on glycemic control

Change in HbA1c levels from baseline

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

Safety as measured by effect of ARI-3037MO on gastrointestinal systems; episodes of nausea, vomiting and diarrhea

occurrence of GI symptoms

Full Information

NCT ID

NCT02574325

First Posted

October 8, 2015

Last Updated

August 5, 2016

Sponsor

Arisaph Pharmaceuticals Inc

1. Study Identification

Unique Protocol Identification Number

NCT02574325

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

October 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Arisaph Pharmaceuticals Inc

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nonalcoholic Steatohepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Arm Title

ARI-3037MO

Arm Type

Experimental

Arm Description

ARI-3037MO

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Control

Intervention Type

Drug

Intervention Name(s)

ARI-3037MO

Intervention Description

Treatment

Primary Outcome Measure Information:

Title

Efficacy as measured by change in intra hepatic fat content

Description

Change in intra hepatic fat content by MRI

Time Frame

24 wks

Title

Efficacy as measured by change in plasma ALT levels

Description

Change in plasma ALT levels from baseline

Time Frame

24 wks

Title

Efficacy as measured by change in plasma TG levels

Description

Change in plasma TG levels from baseline

Time Frame

24 wks

Secondary Outcome Measure Information:

Title

Safety as measured by the occurrence of flushing (number of episodes) and itching (number of episodes)

Description

Occurrence of cutaneous symptoms

Time Frame

24 wks

Title

Safety as measured by effect of ARI-3037MO on on glycemic control

Description

Change in HbA1c levels from baseline

Time Frame

24 wks

Title

Safety as measured by effect of ARI-3037MO on serum bilirubin, alkaline phosphatase, Prothrombin time and plasma albumin levels

Description

Change of liver function tests from baseline

Time Frame

24 wks

Title

Safety as measured by effect of ARI-3037MO on gastrointestinal systems; episodes of nausea, vomiting and diarrhea

Description

occurrence of GI symptoms

Time Frame

24 wks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female patients ≥ 18 years of age at study entry Female patients must be of nonchildbearing potential Have a stable diet and agree to maintain this diet throughout the study Have not gained or lost ≥ 10 lbs (4.5 kg) of body weight within 6months prior to Screening Visit 1 Have a body mass index (BMI) between 28 and 45 kg.m-2, inclusive 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. Have HbA1c of < 9.5 Have a intrahepatic fat content of ≥ 10% confirmed by liver MRI 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. 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: 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) Autoimmune hepatitis Primary biliary cirrhosis Sclerosing cholangitis Hereditary hemochromatosis History of chronic / repeat blood transfusion (i.e., ≥ 20 units of blood) Alpha-1 anti-trypsin deficiency Wilson's disease Thyroid disease Bariatric surgery within 5 years prior to Screening Visit 1 Hepatic disease due to substance abuse 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 Currently taking thiazolidines (glitazone therapy, i.e., Rosiglitazone, Pioglitazone) Liver biopsy in the past 90 days with negative results for cirrhosis and steatosis No evidence of hepatic decompensation or elevated serum bilirubin > 1.5 times the upper limit of normal Estimated glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease equation Known substance abuse Current smoker or a history of smoking (> 10 cigarettes, > 3 cigars or > 3 pipes/day) 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 Currently participating in another clinical study

Facility Information:

Facility Name

Gastroenterology & Hepatology CRU, St Louis University

City

St Louis

State/Province

Missouri

ZIP/Postal Code

63104

Country

United States

12. IPD Sharing Statement

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

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