Nonalcoholic Steatohepatitis (NASH)Phase 2NCT04616014
A Study of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH)
A Phase 2 study testing ORMD-0801 QD in people with Nonalcoholic Steatohepatitis (NASH), run by Oramed, Ltd. at 1 site in Belgium.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis (NASH)
- What is being tested?
- ORMD-0801 QD
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Mar 2021to 15 Sep 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 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.
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- 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
- vasectomised partner (is the sole sexual partner of the WOCBP participating in the trial)
- sexual abstinence
- Acceptable methods include:
- Double barrier methods of contraception include male condoms plus spermicide, diaphragm with spermicide plus male condom, cervical cap with spermicide plus male condom. 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 the study drug.
- since last menstrual cycle with menopausal levels of FSH (FSH>40), b) who are surgically menopausal (surgical sterility defined by tubal occlusion, bilateral oophorectomy, bilaterally or hysterectomy).
- 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 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.
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 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.
- 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 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.
- 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
1 site in 1 country.
About this study
Official title: An Open-Label Multi-Center Study to Assess the Safety and Potential of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH)
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)
Read the detailed description
An Open-Label Multi-Center 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)
- Being tested
- ORMD-0801 QD
- Medical subject headings
- 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 QDDrug
Also called Oral Insulin
16 mg, QD, two capsules, 8 mg each.
| Study group | Role | What they receive |
|---|---|---|
| ORMD-0801 QD | Experimental | 16 mg QD, daily, in the morning (two capsules of ORMD--801, 8 mg each Receives: Drug: ORMD-0801 QD |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
The change in liver fat content measured by MRI-Proton Density Fat Fraction from week -6 to week 12 MR PDFF is expressed as a fat percentage in the liver.
Change in MR PDFF = MR PDFF (week 12) - MR PDFF( Screening)
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.
Measured: Week -6 (screening) and Week 12
Change From Screening in Liver Fibrosis (Elasticity)
Change from screening in Mean Transient Elasticity (Fibrosis) measured in kPA (kilo Pascal).
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.
Measured: Week -6 (Screening) and Week 12
Change From Screening in Liver Steatosis
Change in liver steatosis as measured by FibroScan Controlled Attenuation Parameter (CAP) in units of dB/meter. Mean fibrosis score (severity scale of liver fibrosis) measured at screening (week -6) and week 12. Fibrosis Score CAP measures the 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.
A biostatistician reviewed the study data and determined that it is of poor quality and cannot be properly analyzed.
Conclusions about this study cannot be made based on the study data.
Measured: Week -6 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2020
- Study start1 Mar 2021
- Primary completion1 Jul 2022
- Study completion15 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open, multi-center study
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oramed, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Miriam Kidron, PhD, Study chair, Oramed, Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04616014
- Sponsor's protocol ID
- ORA-D-N01B
- Status last verified
- Mar 2024
- First submitted
- 28 Oct 2020
- Last updated
- 29 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 20494470Vernon 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 21623852Campos 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.
PubMed 18433022
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Multi-Center Study to Assess the Safety and Potential of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT04616014
- Acronym / sponsor ID
- ORA-D-N01B
- Conditions
- Nonalcoholic Steatohepatitis (NASH)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Oramed, Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 1 Jul 2022 (actual)
- Study completion
- 15 Sep 2022 (actual)
- First posted
- 4 Nov 2020 (actual)
- Results
- Posted 29 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
An Open-Label Multi-Center Study to Assess the Safety and Potential of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients with Nonalcoholic Steatohepatitis (NASH)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open, multi-center study
| Arm | Type | Receives |
|---|---|---|
| ORMD-0801 QD | Experimental | Drug: ORMD-0801 QD16 mg QD, daily, in the morning (two capsules of ORMD--801, 8 mg each |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ORMD-0801 QDAlso: Oral Insulin16 mg, QD, two capsules, 8 mg each. | Drug | ORMD-0801 QD |
Primary outcome
Number of Participants With Treatment-related Adverse Events.
Time frame: Week -6 through Week 12 inclusive
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.
3 secondary outcomes
Change From Screening in Liver Fat Content as Measured by MRI Proton Density Fat Fraction (MR PDFF)
Time frame: Week -6 (screening) and Week 12
Change From Screening in Liver Fibrosis (Elasticity)
Time frame: Week -6 (Screening) and Week 12
Change From Screening in Liver Steatosis
Time frame: Week -6 and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20494470Ratziu 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.
- Background: PubMed 21623852Vernon 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.
- Background: PubMed 18433022Campos 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miriam Kidron, PhD study chair
Oramed, Ltd.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ORMD-0801 QD in people with Nonalcoholic Steatohepatitis (NASH), run by Oramed, Ltd. at 1 site in Belgium.
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 23 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 29 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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. 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 29 Mar 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 Participants With Treatment-related Adverse Events. (time frame: Week -6 through Week 12 inclusive). 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 NCT04616014, which also lists 3 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 29 Mar 2024.