A Study of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH)

NCT04616014 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ORA-D-N01B
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

A Study to Assess the Safety and Potential of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients with Nonalcoholic Steatohepatitis (NASH)

Conditions

Nonalcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events.

  The safety of Oral Insulin will be measured by the number of treatment-related adverse events according to CTCAE version 5.0 A biostatistician reviewed the study data and determined that it is of poor quality and cannot be appropriately analyzed. Conclusions about this study cannot be made based on the study data.

  Week -6 through Week 12 inclusive

Secondary Outcomes (3)

• Change From Screening in Liver Fat Content as Measured by MRI Proton Density Fat Fraction (MR PDFF)

  Week -6 (screening) and Week 12

• Change From Screening in Liver Fibrosis (Elasticity)

  Week -6 (Screening) and Week 12

• Change From Screening in Liver Steatosis

  Week -6 and Week 12

Study Arms (1)

ORMD-0801 QD

EXPERIMENTAL

16 mg QD, daily, in the morning (two capsules of ORMD--801, 8 mg each

Drug: ORMD-0801 QD

Interventions

ORMD-0801 QD DRUG

16 mg, QD, two capsules, 8 mg each.

Also known as: Oral Insulin

ORMD-0801 QD

Eligibility Criteria

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

You may qualify if:

• Male or female aged 18-70 years.
• BMI ≥25.
• 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 \> 6.5%28 or on treatment with at least one and no more than three of the following oral anti-diabetic medications, metformin, sulfonylurea, DPP-4 inhibitors, oral GLP-1 receptor agonists (semaglutide), SGLT-2 inhibitor, or Thiazolidinediones (TZDs).
• Diagnosis of NAFLD by non-invasive determination of hepatic steatosis grade S1, defined as hepatic steatosis\>8%. by MRI- PDFF and CAP FibroScan ≥ 238 dB/m.
• Liver enzyme abnormalities: ULN≤5 times.
• Fibrosis score 21≤F≤3 as defined by FibroScan measurement (Liver stiffness measurement, LSM) of 6 ≤ LSM ≤ 12 kPa.
• Signature of the written informed consent.
• Negative urineserum pregnancy test at Screening study entry for women of childbearing potential (WCBP).
• Females must have a negative urine pregnancy test result at screening, prior to the start of the run-in period, at initiation of active dosing and every 4 weeks till the end of the study. 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, one of which must be a highly effective method from the time of screening to the last dosing study visit (22 weeks).
• Highly effective methods include:
• combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal or transdermal) associated with inhibition of ovulation
• progestogen-only hormonal contraception (oral, injectable or implantable) associated with inhibition of ovulation
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion

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-1 antitrypsin deficiency, alcohol liver disease, drug induced liver disease) at the time of enrolment.
• ALT or AST \> 5 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 (264.6 lbs.).
• 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 enrolment.
• History of bariatric surgery.
• Uncontrolled blood pressure BP ≥150/≥95.
• Non-type 2 DM (type 1, endocrinopathy, genetic syndromes etc.).
• Patients with HIV.
• Daily alcohol intake \>20 g/day (2 units/day) for women and \>30 g/day (3 units/day) for men.
• Treatment with anti-diabetic medications other than at least one and no more than three of the following: metformin, sulfonylurea, DPP-4 inhibitors, oral GLP-1 receptor agons metformin and more than two of the following medications sulfonylurea, DPP-4 inhibitors, oral GLP-1 receptor agonists (semaglutide), SGLT-2 inhibitors, or TZDs.
• Fibrates and statins not provided on a stable dose in the last 6 months.

Sponsors & Collaborators

• Oramed, Ltd.: lead

Study Sites (1)

Universitaire Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Related Publications (3)

• 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

• Campos GM, Bambha K, Vittinghoff E, Rabl C, Posselt AM, Ciovica R, Tiwari U, Ferrel L, Pabst M, Bass NM, Merriman RB. A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients. Hepatology. 2008 Jun;47(6):1916-23. doi: 10.1002/hep.22241.

  PMID: 18433022 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

A biostatistician reviewed the study data and determined that it is of poor quality and cannot be appropriately analyzed. Conclusions about this study cannot be made based on the study data.

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Oramed, Ltd.

miriam@oramed.com

972-2-566-0001

Study Officials

• Miriam Kidron, PhD

  Oramed, Ltd.

  STUDY CHAIR

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
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open, multi-center study

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: November 4, 2020
• Study Start: March 1, 2021
• Primary Completion: July 1, 2022
• Study Completion: September 15, 2022
• Last Updated: March 29, 2024
• Results First Posted: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)