CompletedNCT04618744Updated Aug 7, 2024Results posted

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

A Phase 2 interventional study of ORMD-0801 (Insulin) capsule 8 mg BD and Placebo in Diabetes Mellitus, Type 2 and NASH - Nonalcoholic Steatohepatitis, sponsored by Oramed, Ltd.. Completed at 3 sites in 2 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-08-07.

Sponsored by Oramed, Ltd. · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 32
Allocation: Randomized
Ages: 18 Years to 70 Years
Sex: All

Study 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 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.

Conditions studied

Diabetes Mellitus, Type 2
NASH - Nonalcoholic Steatohepatitis

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Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.
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).

Exclusion criteria

Exclusion Criteria:

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 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:
i. History of severe claustrophobia impacting the ability to perform MRI during the study, even despite mild sedation/treatment with as anxiolytic.

ii. Subjects with metal implants, devices, paramagnetic objects contained within the body, and excessive or metal-containing tattoos.

iii. 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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 32 participants (actual)

Study arms

Placebo comparator
Placebo
Fish oil
Other: Placebo
Experimental
ORMD-0801 (Insulin) capsule 8 mg BD
ORMD-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
Drug: ORMD-0801 (Insulin) capsule 8 mg BD

Interventions

DrugORMD-0801 (Insulin) capsule 8 mg BD
8 mg ORMD-0801, 1 capsule, twice a day, once in the morning and once in the evening.
Also known as: Oral Insulin
OtherPlacebo
Matching Placebo
Also known as: Fish oil

What researchers measure

Primary outcomes

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.
Time frame: Screening through Week 16

Secondary outcomes

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.
Time frame: Baseline and Week 12 (Visit 8)
Percent Change From Baseline of Median MRPDFF of Whole Liver
The percent change in MR PDFF from baseline to Week 12 of Whole Liver
Time frame: Baseline and Week 12 (Visit 8)
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.
Time frame: Baseline and Week 12
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
Time frame: Screening and Week 12 (Visit 8)
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.
Time frame: Baseline and Week 12 (Visit 8)
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)
Time frame: Baseline and Week 12 (Visit 8)
Mean MRPDFF of Liver Segment 3
Mean MRPDFF of Liver Segment measured at baseline and Week 12
Time frame: Baseline and Week 12 (Visit 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
Time frame: Baseline and Week 12 (Visit 8)
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.
Time frame: Screening and Week 12 (Visit 8)
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
Time frame: Screening and Week 12 (Visit 8)
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)
Time frame: Screening and Week 12 (Visit 8)
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)
Time frame: Screening and Week 12 (Visit 8)
Median MRPDFF of Liver Segment 8
Median MRPDFF of Liver Segment 8 measured at baseline and Week 12 (Visit 8)
Time frame: Baseline and Week 12 (Visit 8)
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).
Time frame: Baseline and Week 12 (Visit 8)
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.
Time frame: Baseline and Week 12 (Visit 8)
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)
Time frame: Baseline and Week 12 (Visit 8)
Liver Steatosis
Liver steatosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M)
Time frame: Baseline and Week 12 (Visit 8)
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)
Time frame: Baseline and Week 12 (Visit 8)
Liver Fibrosis
Liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).
Time frame: Baseline and Week 12 (Visit 8)
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).
Time frame: Baseline and Week 12 (Visit 8)

Results

Posted Aug 7, 2024

Participant flow

Participant flow — Overall Study
Milestone	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Started	11	21
Completed	11	19
Not completed	0	2
Withdrew: Adverse event	0	1
Withdrew: Withdrawal by subject	0	1

Outcome measures

PrimaryNumber 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.

Time frame:: Screening through Week 16
Reported as:: Number · Adverse Events

Number of Treatment-Emergent Adverse Events
Adverse Events	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Number of Treatment-Emergent Adverse Events	0	2

SecondaryMedian 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.

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · Percent fat (MRPDFF)

Median MRPDFF at Baseline and Week 12 of Whole Liver
Percent fat (MRPDFF)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Median MRPDFF at Baseline	24.350 (9.80 to 31.90)	15.340 (5.34 to 27.20)
Median MRPDFF (percentage fat) at Week 12	17.300 (3.66 to 29.50)	13.300 (3.33 to 26.80)

SecondaryPercent Change From Baseline of Median MRPDFF of Whole Liver

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

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · percent change

Percent Change From Baseline of Median MRPDFF of Whole Liver
percent change	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change From Baseline of Median MRPDFF of Whole Liver	-1.103 (-28.97 to 16.33)	-7.105 (-65.78 to 59.18)

SecondaryMean 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.

Time frame:: Baseline and Week 12
Reported as:: Mean · percentage of fat

Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver
percentage of fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Mean MRPDFF of Whole Liver at Baseline	21.558 ± 8.2072	15.683 ± 6.1605
Mean MR PDFF of Whole Liver at Week 12	17.414 ± 8.6331	14.274 ± 6.8032

SecondaryPercent 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

Time frame:: Screening and Week 12 (Visit 8)
Reported as:: Mean · Percentage of change in MRPDFF

Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver
Percentage of change in MRPDFF	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver	-6.526 ± 15.3158	-7.489 ± 27.3972

SecondaryMedian 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.

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · percentage fat

Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3
percentage fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Median MRPDFF Liver Segment 3 Baseline	21.10 (6.97 to 33.50)	13.900 (5.34 to 26.90)
Median MRPDFF Liver Segment 3 Week 12	15.150 (3.11 to 28.70)	11.900 (3.28 to 26.43)

SecondaryPercent 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)

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · percentage change

Percent Change From Baseline of Median MRPDFF of Liver Segment 3
percentage change	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change From Baseline of Median MRPDFF of Liver Segment 3	0.000 (-26.97 to 26.40)	-6.424 (-66.67 to 10.19)

SecondaryMean MRPDFF of Liver Segment 3

Mean MRPDFF of Liver Segment measured at baseline and Week 12

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Mean · percentage fat

Mean MRPDFF of Liver Segment 3
percentage fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
MRPDFF of Liver Segment 3 at baseline	20.617 ± 9.1032	14.560 ± 5.3974
MR PDFF of Liver Segment 3 at Week 12	16.610 ± 9.2736	13.119 ± 6.2239

SecondaryPercent 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

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Mean · percentage of Change in MR PDFF

Percent Change of Mean MRPDFF of Liver Segment 3
percentage of Change in MR PDFF	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change of Mean MRPDFF of Liver Segment 3	0.105 ± 17.2630	-10.763 ± 20.9231

SecondaryMedian 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.

Time frame:: Screening and Week 12 (Visit 8)
Reported as:: Median · percentage of liver fat

Median MR PDFF of Liver Segment 6
percentage of liver fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Median MRPDFF of Liver Segment 6 Baseline	22.900 (8.76 to 37.00)	15.420 (4.81 to 30.00)
Median MRPDFF of Liver Segment 6 Week 12	15.400 (3.28 to 27.40)	12.600 (5.19 to 27.13)

SecondaryPercent 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

Time frame:: Screening and Week 12 (Visit 8)
Reported as:: Median · percent change

Percent Change From Baseline of Median MR PDFF of Liver Segment 6
percent change	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change From Baseline of Median MR PDFF of Liver Segment 6	-4.965 (-37.19 to 15.01)	-6.488 (-41.49 to 54.63)

SecondaryMean 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)

Time frame:: Screening and Week 12 (Visit 8)
Reported as:: Mean · percentage liver fat

Mean MR PDFF of Liver Segment 6
percentage liver fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Mean MRPDFF of liver segment 6 at Baseline	22.174 ± 8.9629	15.828 ± 7.3523
Mean MRPDFF of Liver segment 6 at Week 12	16.226 ± 8.4452	14.009 ± 7.1855

SecondaryPercent 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)

Time frame:: Screening and Week 12 (Visit 8)
Reported as:: Mean · percent change

Percent Change From Baseline of Mean MR PDFF of Liver Segment 6
percent change	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change From Baseline of Mean MR PDFF of Liver Segment 6	-9.891 ± 15.3865	-9.310 ± 21.7602

SecondaryMedian MRPDFF of Liver Segment 8

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

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · percentage liver fat

Median MRPDFF of Liver Segment 8
percentage liver fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Median MRPDFF of Liver Segment 8 at baseline	25.100 (8.06 to 31.20)	15.600 (6.63 to 28.20)
Median MR PDFF of Liver Segment 8 at Week 12	18.200 (3.66 to 27.90)	13.500 (3.27 to 28.03)

SecondaryPercent 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).

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · percent change of the median MRPDFF

Percent Change in Median MRPDFF of Liver Segment 8
percent change of the median MRPDFF	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change in Median MRPDFF of Liver Segment 8	-6.376 (-35.71 to 12.54)	-5.419 (-65.18 to 32.75)

SecondaryMean 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.

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Mean · percentage fat

Mean MRPDFF of Liver Segment 8
percentage fat	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Mean MRPDFF of liver segment 8 at Baseline	22.565 ± 7.8978	16.071 ± 6.3147
Mean MRPDFF of Liver segment 8 at Week 12	17.451 ± 2.8338	14.817 ± 7.1945

SecondaryPercent 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)

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Mean · percentage change in MRPDFF

Percent Change From Baseline in Mean MRPDFF of Liver Segment 8
percentage change in MRPDFF	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Percent Change From Baseline in Mean MRPDFF of Liver Segment 8	17.451 ± 8.6343	14.817 ± 7.1945

SecondaryLiver Steatosis

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

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · dB/M

Liver Steatosis
dB/M	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Median Liver Steatosis Baseline	335 (276 to 345)	329 (299 to 357)
Median Liver Steatosis Week 12	345.0 (320.0 to 360.0)	329.0 (279.0 to 351.0)

SecondaryChange 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)

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · dB/M

Change in Liver Steatosis From Baseline
dB/M	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Change in Liver Steatosis From Baseline	13.0 (0.0 to 38.0)	-16.0 (-38.0 to 22)

SecondaryLiver Fibrosis

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

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · kPa (kilo Pascals)

Liver Fibrosis
kPa (kilo Pascals)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Median Liver Fibrosis Baseline	8.4 (6.4 to 9.0)	8.6 (6.7 to 9.2)
Median Liver Fibrosis Week 12	7.4 (6.5 to 8.7)	7.4 (6.4 to 9.7)

SecondaryChange 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).

Time frame:: Baseline and Week 12 (Visit 8)
Reported as:: Median · kPa (kilo Pascals)

Change From Baseline of Liver Fibrosis
kPa (kilo Pascals)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Change From Baseline of Liver Fibrosis	0.3 (-2.6 to 2.3)	-0.8 (-2.5 to 3.8)

Adverse events

Collected over Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo	0/11 (0%)	1/11 (9.1%)	4/11 (36.4%)
ORMD-0801 (Insulin) Capsule 8 mg BD	0/21 (0%)	1/21 (4.8%)	7/21 (33.3%)

Most frequent serious events

Most frequent serious events
Event	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Atrial fibrillationCardiac disorders	1/11	0/21
Gastrointenstinal hemorrhageGastrointestinal disorders	0/11	1/21

Most frequent other events

Most frequent other events
Event	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD
Addominal DistentionGastrointestinal disorders	0/11	5/21
NauseaGastrointestinal disorders	0/11	2/21
Atrial FibrillationCardiac disorders	1/11	1/21
Atrial FlutterCardiac disorders	1/11	0/21
COVID-19Infections and infestations	1/11	0/21
HyperglycemiaMetabolism and nutrition disorders	1/11	0/21
HypokalaemiaMetabolism and nutrition disorders	0/11	1/21

Baseline characteristics

Intent to Treat

Age, Continuous
Age, Continuous(Years)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
Mean	56.73 ± 10.355	58.67 ± 7.565	58.00 ± 8.508

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
Female	5	7	12
Male	6	14	20

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
Hispanic or Latino	7	11	18
Not Hispanic or Latino	4	10	14
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
American Indian or Alaska Native	0	0	0
Asian	1	0	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	1	1
White	10	19	29
More than one race	0	1	1
Unknown or Not Reported	0	0	0

Body Mass Index (BMI)
Body Mass Index (BMI)(Kg/m^2)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
Mean	32.109 ± 4.5496	33.567 ± 5.2981	33.066 ± 5.0281

Childbearing Status
Childbearing Status(Participants)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
Of Childbearing Potential	0	0	0
Surgically Sterilized	2	4	6
At least 24 months Post-Menopausal	3	3	6
Not Applicable	6	14	20

Median Magnetic Resonance Proton Fat Fraction (MRPDFF)
Median Magnetic Resonance Proton Fat Fraction (MRPDFF)(percent liver fat)	Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD	Total
Median	21.100 (6.97 to 33.50)	13.900 (5.34 to 26.90)	14.250 (5.34 to 33.50)

Study locations

3 sites

Orange County Research Center
Tustin, California 92780, United States
Hadassah Medical Center
Jerusalem, International/Other, Israel
Tel Aviv Sourasky Medical Center- Ichilov Hospital
Tel Aviv, International/Other 6423906, Israel

References and documents

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 ↗

Study documents

Protocol and statistical analysis plan · Aug 25, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT04618744
Lead sponsor: Oramed, Ltd.
Collaborators: Integrium
Responsible party: Sponsor
First posted: Nov 6, 2020
Start date: Nov 24, 2020
Primary completion: Jun 27, 2022
Completion: Jun 27, 2022
Results posted: Aug 7, 2024
Last update: Aug 7, 2024

Study contacts

Miriam Kidron, Ph.D.

study director · Oramed, Ltd.

Joel M Neutel, M. D.

principal investigator · Integrium

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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