A Pilot Study to Assess the Safety of Oral Insulin in Patients With Nonalcolholic Steatohepatitis (NASH)

March 12, 2024 updated by: Oramed, Ltd.

An Open-Label Pilot Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Potential of Oral Insulin to Reduce Liver Fat Content and Fibrosis in Patients With Nonalcolholic Steatohepatitis (NASH)

This is an open, pilot study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM or pre-diabetes. The study will consist of a Screening, placebo run-in, treatment phase and end-of-study phase.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This exploratory study will first enroll 10 patients with NASH and type 2 DM, to evaluate the safety of oral insulin and to measure the change in liver fat content.

At the completion of their 4-week follow-up period, results will be presented to the Helsinki Committee. Following approval, an additional 20 patients will be enrolled. The size of the study population was determined by the investigator (with literature review) to be sufficient to show trends of reducing liver fat content by analysis of MRI PDFF (MRI-Proton Density Fat Fraction) images, the FibroMax™ Test and Fibroscan® including Controlled Attenuation Parameter (CAP™). CAP™ is a measure of the ultrasound attenuation to quantify steatosis in the liver.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel
        • Hadassah Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Known type 2 DM according to American Diabetic Association (one of the three needed): Fasting Plasma Glucose ≥126 mg/dl or 2h postprandial (PG) following 75g OGTT ≥ 200 mg/dl or HbA1C > 5.7% or on treatment with metformin
  • Abdominal ultrasound (US) proven fatty liver performed within 6 months before randomization, confirmed by central US.
  • Fat concentration in the liver of S2 (moderate steatosis, 6-32% hepatocytes with steatosis) or more as measured by Fibromax.
  • Signature of the written informed consent.
  • Negative pregnancy test at study entry for females of child bearing potential.
  • Females must have a negative urine pregnancy test result at screening, prior to the start of the run-in period, and at initiation of active dosing. A negative urine and serum pregnancy test must be obtained prior to active dosing. Males and females of childbearing potential must use two methods of contraception.
  • Females of non-childbearing potential are defined as postmenopausal who a) had more than 24 months since last menstrual cycle with menopausal levels of FSH, b) who are surgically menopausal.
  • For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening with BP < 150/<95 mmHg
  • Patients previously treated with vitamin E (>400IU/day).
  • Glycaemia must be controlled (Glycosylated Hemoglobin A1C ≤9%) while any HbA1C increment should not exceed 1% during 6 months prior to enrolment).

Exclusion Criteria:

  • Patients with active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, genetic hemochromatosis, Wilson disease, alpha 1antitripsin deficiency, alcohol liver disease, drug induced liver disease) at the time of randomization.
  • ALT or AST ≥ 2 times ULN
  • Abnormal synthetic liver function (serum albumin ≤3.5gm%, INR >1.3).
  • Known alcohol and/or any other drug abuse or dependence in the last five years.
  • Weight >120 Kg
  • Known history or presence of clinically significant cardiovascular, gastrointestinal, metabolic (other than diabetes mellitus), neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephrotic syndrome.
  • History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including bile salt metabolites (e.g. inflammatory bowel disease (IBD), previous intestinal (ileal or colonic) operation, chronic pancreatitis, celiac disease or previous vagotomy.
  • Weight loss of more than 5% within 6 months prior to randomization.
  • History of bariatric surgery.
  • Uncontrolled blood pressure BP ≥150/95.
  • Non type 2 DM (type I, endocrinopathy, genetic syndromes etc).
  • Patients with HIV.
  • Daily alcohol intake >20 g/day for women and >30 g/day for men.
  • Treatment anti-diabetic medications other than metformin, such as DPP-4 inhibitors, GLP-1 receptor agonists, TZDs, etc.
  • Metformin, Fibrates, Statins, not provided on a stable dose in the last 6 months.
  • Patients who are treated with Valproic acid, Tamoxifen, Methotrexate, Amiodaron.
  • Chronic treatment with antibiotics (e.g. Rifaximin).
  • Homeopathic and/or Alternative treatments.
  • Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone >2X the upper limit of normal (UNLN).
  • Patients with renal dysfunction: eGFR< 40 ml/min.
  • Unexplained serum creatinine phosphokinase

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Insulin
treatment
Biological: Oral Insulin
all patients will receive treatment regimen of a soft gel capsule of ORMD-0801.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in MRI-Proton Density Fat Fraction (MRI-PDFF)
Time Frame: Two timepoints: Baseline (week 0) and Week 12
Absolute Change in MRI-Proton Density Fat Fraction (expressed as percent fat in the liver) from baseline to week 12
Two timepoints: Baseline (week 0) and Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Transient Elastography Measurement (Fibroscan)
Time Frame: Two timepoints: Baseline (week 0) and Week 12
Mean Transient elasticity, measured in kPA (kilo Pascal),
Two timepoints: Baseline (week 0) and Week 12
Mean Fibrosis Score CAP™ (FibroMax)
Time Frame: Two timepoints: Baseline (week 0) and Week 12
Mean fibrosis score (severity scale of liver fibrosis) measured at baseline and week 12. Fibrosis Score CAP measures the amount of steatosis (fatty change) in the liver. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m with higher values indicating more fatty change
Two timepoints: Baseline (week 0) and Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oramed, Ltd.

Collaborators

Hadassah Medical Organization

Investigators

  • Principal Investigator: Rifaat Safadi, M.D., Hadassah Medical Organization

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2018

Primary Completion (Actual)

March 1, 2020

Study Completion (Actual)

April 1, 2020

Study Registration Dates

First Submitted

December 24, 2015

First Submitted That Met QC Criteria

January 8, 2016

First Posted (Estimated)

January 12, 2016

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORA-D-N01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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