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

NCT02653300 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ORA-D-N01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Alcoholic Steatohepatitis (NASH); Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in MRI-Proton Density Fat Fraction (MRI-PDFF)

  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 Outcomes (2)

• Mean Transient Elastography Measurement (Fibroscan)

  Two timepoints: Baseline (week 0) and Week 12

• Mean Fibrosis Score CAP™ (FibroMax)

  Two timepoints: Baseline (week 0) and Week 12

Study Arms (1)

Oral Insulin

EXPERIMENTAL

treatment

Biological: Oral Insulin

Interventions

Oral Insulin BIOLOGICAL

all patients will receive treatment regimen of a soft gel capsule of ORMD-0801.

Oral Insulin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oramed, Ltd.: lead
• Hadassah Medical Organization: collaborator

Study Sites (1)

Hadassah Medical Center

Jerusalem, Israel

Location

Related Publications (4)

• Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.

  PMID: 22488764 BACKGROUND

• Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol. 2010 Aug;53(2):372-84. doi: 10.1016/j.jhep.2010.04.008. Epub 2010 May 7. No abstract available.

  PMID: 20494470 BACKGROUND

• Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.

  PMID: 21623852 BACKGROUND

• Lin SC, Heba E, Bettencourt R, Lin GY, Valasek MA, Lunde O, Hamilton G, Sirlin CB, Loomba R. Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging. Aliment Pharmacol Ther. 2017 Mar;45(6):844-854. doi: 10.1111/apt.13951. Epub 2017 Jan 24.

  PMID: 28116801 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Insulin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This is a pilot study with ten subjects enrolled, and eight subjects analyzed.

Results Point of Contact

• Title: Miriam Kidron, Ph.D.
• Organization: Oramed Pharmaceuticals

miriam@oramed.com

+972-2-566-0100

Study Officials

• Rifaat Safadi, M.D.

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2015
• First Posted: January 12, 2016
• Study Start: September 20, 2018
• Primary Completion: March 1, 2020
• Study Completion: April 1, 2020
• Last Updated: March 13, 2024
• Results First Posted: September 23, 2021

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)