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Diabetes Mellitus, Type 2Phase 2NCT04618744

A Study to Assess the Safety and Efficacy of Oral Insulin in T2DM Patients With Nonalcoholic Steatohepatitis (NASH)

A Phase 2 study testing ORMD-0801 (Insulin) capsule 8 mg BD in people with Diabetes Mellitus, Type 2 and NASH - Nonalcoholic Steatohepatitis, run by Oramed, Ltd. at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a double-blind, randomized, placebo-controlled, multi-center study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
ORMD-0801 (Insulin) capsule 8 mg BD
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
3 sitesin 2 countries
Study dates
24 Nov 2020to 27 Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 metformin only or metformin in addition to no more than two of the following medications sulfonylurea, DPP-4 inhibitors, GLP-1 receptor agonists, 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.
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  • Signature of the written informed consent.
  • Negative urine serum pregnancy test at Screening study entry for females of childbearing potential (WCBP).
  • WCBP must have a negative urine pregnancy test result prior to the start of the run-in period and initiation if 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 (double barrier method), one of which must be an acceptable barrier method from the time of screening to the last dosing study visit (22 weeks). Barrier methods of contraception include male condoms plus spermicide, diaphragm with spermicide plus male condom, cervical cap with spermicide plus male condom, or oral contraceptives. Acceptable methods of birth control include abstinence, oral contraceptives, surgical sterilization, vasectomy, the contraceptive patch, and the contraceptive ring. If a subject is not usually sexually active but becomes active, he or his partner should use medically accepted forms of contraception. Sperm donations will not be allowed for the duration of the study and for 90 days after the last dose of study drug.
  • 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 (FSH Level > 40), b) who are surgically menopausal (surgical sterility defined by tubal occlusion, bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • For hypertensive patients, hypertension must be controlled by a stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study) with BP < 150/<95 mmHg
  • Patients previously treated with vitamin E (>400IU/day), Polyunsaturated fatty acid (>2g/day) or Ursodeoxycholic acid fish oil can be included if drugs are stopped at least 3 months prior to enrolment and up to the end of the study.
  • Glycaemia must be controlled (Glycosylated Hemoglobin A1C ≤8.5%) while any HbA1C increment should not exceed 1% during 6 months prior to enrolment).

Who cannot join

  • 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.
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  • 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 metformin and more than two of the following medications sulfonylurea, DPP-4 inhibitors, GLP-1 receptor agonists, TZDs
  • Metformin, fibrates, statins, not provided on a stable dose in the last 6 months.
  • Patients who are treated with valproic acid, Tamoxifen, methotrexate, amiodarone.
  • Chronic treatment with antibiotics (e.g. Rifaximin).
  • Homeopathic and/or Alternative treatments. Any treatment must be stopped before the screening period.
  • Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone >2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
  • Patients with renal dysfunction: eGFR< 40 ml/min.
  • Unexplained serum creatinine phosphokinase (CPK) >3X the upper limit of normal (ULN). Patients with a reason for CPK elevation may have the measurement repeated prior to enrolment; a CPK retest > 3X ULN leads to exclusion.
  • Subjects meeting criteria for contraindication for MRI - including the following:
  • History of severe claustrophobia impacting the ability to perform MRI during the study, even despite mild sedation/treatment with as anxiolytic.
  • Subjects with metal implants, devices, paramagnetic objects contained within the body, and excessive or metal-containing tattoos.
  • Subjects unable to lie still within the environment of the MRI scanner or maintain a breath-hold for the required period to acquire images, even despite mild sedation/treatment with an anxiolytic.
  • The subject participated in a clinical research study involving a new chemical entity within 4 weeks of study entry.
  • Known allergy to soy.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Israel2 sites

  • Hadassah Medical Center

    Jerusalem, International/Other

  • Tel Aviv Sourasky Medical Center- Ichilov Hospital

    Tel Aviv, International/Other, 6423906

Other trials in Israel

United States1 site

  • Orange County Research Center

    Tustin, California, 92780

Other trials in United States

About this study

Official title: A Double-Blind, Randomized, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH)

This is a double-blind, randomized, placebo-controlled, multi-center study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM.

Read the detailed description

This is a double-blind, randomized, placebo-controlled, multi-center study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM. The study will consist of a Screening Phase, Placebo Run-in Phase, Treatment Phase and an End-of-Study Phase. Approximately 36 subjects will be randomized in a 2:1 ratio to receive either 8 mg ORMD-0801, 1 capsule twice a day (once in the morning approximately 30 to 45 minutes prior to breakfast and no later than 10 AM, and once at night between 8 PM to Midnight and no sooner than 1 hour after dinner) or matching placebo.

Being tested
ORMD-0801 (Insulin) capsule 8 mg BD, Placebo
Medical subject headings
Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ORMD-0801 (Insulin) capsule 8 mg BDDrug

    Also called Oral Insulin

    8 mg ORMD-0801, 1 capsule, twice a day, once in the morning and once in the evening.

  • PlaceboOther

    Also called Fish oil

    Matching Placebo

Study groups in NCT04618744
Study groupRoleWhat they receive
PlaceboPlacebo comparatorFish oil
Receives: Other: Placebo
ORMD-0801 (Insulin) capsule 8 mg BDExperimentalORMD-0801 (insulin) capsule Dose: 8 mg BD Dosage Regimen: 1 capsule twice a day (once in the morning approximately 30 to 45 minutes prior to breakfast and no later than 10 AM, and once at night between 8 PM to Midnight and no sooner than 1 hour after dinner) Mode of Administration: Oral
Receives: Drug: ORMD-0801 (Insulin) capsule 8 mg BD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Treatment-Emergent Adverse Events

    The Number of Treatment-Emergent Adverse Events (TEAE) according to CTCAE version 4.03. A TEAE is an adverse event for which the start date is on or after the date that the treatment began.

    Measured: Screening through Week 16

Secondary outcomes (20)

  1. Median MRPDFF at Baseline and Week 12 of Whole Liver

    Median MRPDFF at Baseline and Week 12 of Whole Liver. Delineation by a central radiologist of the whole liver in the slice with the largest liver cross-section. The Liver was subdivided into 8 sections according to the Coinaud liver segmentation for MRI.

    Measured: Baseline and Week 12 (Visit 8)

  2. Percent Change From Baseline of Median MRPDFF of Whole Liver

    The percent change in MR PDFF from baseline to Week 12 of Whole Liver

    Measured: Baseline and Week 12 (Visit 8)

  3. Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver

    Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver at Baseline and Week12. The Whole liver was delineated by a central radiologist. The liver was subdivided into 8 sections according to the Coinaud liver segmentation for MRI.

    Measured: Baseline and Week 12

  4. Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver

    The percent change from basline in liver fat content as measured by the mean MRI Proton density Fat Fraction (MR PDFF) at baseline and at week 12 of Whole Liver

    Measured: Screening and Week 12 (Visit 8)

  5. Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3

    Median MRPDFF (percentage fat in the liver) of liver segment 3 as measured by MRI Proton Density Fat Fraction at baseline and at week 12. Delineation by a central radiologist of the Liver Segment 3 in the slice with the largest Liver Segment 3 cross-section.

    Measured: Baseline and Week 12 (Visit 8)

  6. Percent Change From Baseline of Median MRPDFF of Liver Segment 3

    Percent Change from Baseline Median MRPDFF of Liver Segment measured at baseline and Week 12 (Visit 8)

    Measured: Baseline and Week 12 (Visit 8)

  7. Mean MRPDFF of Liver Segment 3

    Mean MRPDFF of Liver Segment measured at baseline and Week 12

    Measured: Baseline and Week 12 (Visit 8)

  8. Percent Change of Mean MRPDFF of Liver Segment 3

    Percent change from baseline of mean MR PDFF measurement of liver segment 3 at baseline and week 12

    Measured: Baseline and Week 12 (Visit 8)

  9. Median MR PDFF of Liver Segment 6

    Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8). Delineation by a central radiologist of Liver Segment 6 in the slice with the largest Liver Segment 6 cross-section.

    Measured: Screening and Week 12 (Visit 8)

  10. Percent Change From Baseline of Median MR PDFF of Liver Segment 6

    Percent Change from Baseline of Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12

    Measured: Screening and Week 12 (Visit 8)

  11. Mean MR PDFF of Liver Segment 6

    Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8)

    Measured: Screening and Week 12 (Visit 8)

  12. Percent Change From Baseline of Mean MR PDFF of Liver Segment 6

    Percent Change from Baseline Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8)

    Measured: Screening and Week 12 (Visit 8)

  13. Median MRPDFF of Liver Segment 8

    Median MRPDFF of Liver Segment 8 measured at baseline and Week 12 (Visit 8)

    Measured: Baseline and Week 12 (Visit 8)

  14. Percent Change in Median MRPDFF of Liver Segment 8

    Percent change from baseline in median MRPDFF of Liver segment 8 measured at baseline and week 12 (Visit 8).

    Measured: Baseline and Week 12 (Visit 8)

  15. Mean MRPDFF of Liver Segment 8

    Liver fat percentage of liver segment 8 as measured by MRI Proton Density Fat Fraction (MR PDFF) at baseline and at week 12 (Visit 8). Delineation by a central radiologist of Liver Segment 8 in the slice with the largest Liver Segment 8 cross-section.

    Measured: Baseline and Week 12 (Visit 8)

  16. Percent Change From Baseline in Mean MRPDFF of Liver Segment 8

    Percent change from baseline in MRPDFF of liver segment 8 at baseline and at week 12 (Visit 8)

    Measured: Baseline and Week 12 (Visit 8)

  17. Liver Steatosis

    Liver steatosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M)

    Measured: Baseline and Week 12 (Visit 8)

  18. Change in Liver Steatosis From Baseline

    Change in Liver steatosis from baseline measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M)

    Measured: Baseline and Week 12 (Visit 8)

  19. Liver Fibrosis

    Liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).

    Measured: Baseline and Week 12 (Visit 8)

  20. Change From Baseline of Liver Fibrosis

    The change from baseline in liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).

    Measured: Baseline and Week 12 (Visit 8)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2020
  2. Study start24 Nov 2020
  3. Primary completion27 Jun 2022
  4. Study completion27 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study will consist of a Screening Phase, Placebo Run-in Phase, Treatment Phase, and an End-of-Study Phase. Approximately 36 subjects will be randomized in a 2:1 ratio to receive either 8 mg ORMD-0801, 1 capsule twice a day (once in the morning approximately 30 to 45 minutes prior to breakfast and no later than 10 AM, and once at night between 8 PM to Midnight and no sooner than 1 hour after dinner) or matching placebo.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04618744
Sponsor's protocol ID
ORA-D-N02
Status last verified
Jul 2024
First submitted
1 Nov 2020
Last updated
7 Aug 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 28116801

  • 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.

    PubMed 22488764

  • 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.

    PubMed 20494470

  • 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.

    PubMed 21623852

  • Germain T, Favelier S, Cercueil JP, Denys A, Krause D, Guiu B. Liver segmentation: practical tips. Diagn Interv Imaging. 2014 Nov;95(11):1003-16. doi: 10.1016/j.diii.2013.11.004. Epub 2013 Dec 30.

    PubMed 24388431

  • Ishay Y, Neutel J, Kolben Y, Gelman R, Arbib OS, Lopez O, Katchman H, Mohseni R, Kidron M, Ilan Y. Oral Insulin Alleviates Liver Fibrosis and Reduces Liver Steatosis in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes: Results of Phase II Randomized, Placebo-controlled Feasibility Clinical Trial. Gastro Hep Adv. 2023 Dec 7;3(3):417-425. doi: 10.1016/j.gastha.2023.11.016. eCollection 2024.

    PubMed 39131144

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ORMD-0801 (Insulin) capsule 8 mg BD in people with Diabetes Mellitus, Type 2 and NASH - Nonalcoholic Steatohepatitis, run by Oramed, Ltd. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Israel, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Treatment-Emergent Adverse Events (time frame: Screening through Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04618744, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.

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