Non-alcoholic Steatohepatitis (NASH)
Conditions
Brief summary
This study will evaluate the safety and preliminary efficacy of two dose levels of IMM-124E in reducing liver fat and/or serum alanine aminotransaminase (ALT) compared with placebo.
Detailed description
Subjects who provide voluntary written informed consent will be screened for eligibility. Subjects meeting all of the inclusion and none of the exclusion criteria will be eligible to participate. Eligible subjects will be randomized at the Baseline visit to receive one of the three study treatments three times daily for a period of 24 weeks. Each subject will return to the study clinic for assessment and required study procedures on Day 7, 14 and 28 and every 4 weeks thereafter until Week 24.
Interventions
BIOLOGICALIMM-124E
IMM-124E
OTHERPlacebo
Matched placebo
Sponsors
Immuron Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Provision of written informed consent. 3. Diagnosis of NASH, histologically proven within 12 months of Screening with * NASH activity score (NAS) of 4 or more * cytologic ballooning score of at least 1; * 10% or more macrovescicular steatosis. * Hematoxylin & Eosin (H&E) stained slides and/or paraffin block available for independent assessment. 4. HBA1C of \<9.0 5. Agree to the use of effective contraceptive measures if either male or female of child bearing potential.
Exclusion criteria
1. Presence of vascular liver disease or cirrhosis; 2. Presence of liver disease with other cause (autoimmune, metabolic, medication induced); 3. BMI \<25 kg/m\^2; 4. Alcohol use \>30 g/day; 5. Type 1 diabetes; 6. 6\. History of major bariatric surgery (not including balloon / sleeve gastrectomy); 7. Weight loss or gain of 5kg or more in the past 6 months or \>10% change in bodyweight in the past 12 months; 8. Contraindication for MRI; 9. Inadequate venous access; 10. Lactating/breastfeeding/pregnant at Screening or Baseline; 11. HIV antibody positive, hepatitis B surface antigen positive (HBsAg) or Hepatitis C virus (HCV)-RNA positive; 12. Receiving an elemental diet or parenteral nutrition; 13. Concurrent conditions * Inflammatory bowel disease; * Unstable angina, myocardial infarction, transient ischemic events, or stroke within 24 weeks of Screening; * Ongoing infectious, ongoing multi-systemic immune-mediated and/or concurrent or past malignant disease; * Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or on the interpretation of the study data; 14. Concurrent medications including: * anti-NASH therapy(s) taken for more than 10 continuous days in the last 3 months. These include S-adenosyl methionine (SAM-e), betaine, milk thistle, probiotic supplements (other than yoghurt), vitamin E and gemfibrozil. * NB: If vitamin E or gemfibrozil are used, the dose must be stable and liver biopsy confirming diagnosis of NASH subsequent to commencing treatment; commencing treatment; * Wash out for any of the anti-NASH therapies is as follows: under 10 days no washout required, more than 10 days and up to 3 months treatment requires 6 weeks washout. Any treatment of over 3 months would require to re-biopsy to ensure histological eligibility * thiazolidinediones (glitazones), dipeptidyl peptidase 4 inhibitors (gliptins) or glucagon-like peptide-1 analogs in the last 6 months. If treatment commenced and is stable for more than 6 month prior to the determinant biopsy and the dose is still stable at time of study entry, subjects will be eligible for recruitment. * Allowable anti-diabetic treatment includes metformin and/or sulfonylureas administered at constant dose for at least 2 months prior to study entry. * Subjects treated with Insulin are eligible if clinically stable on insulin treatment (i.e. no recurrent acute hypo-/hyperglycemic episodes diagnosed clinically and by Glucose serum levels of \<50 mg/dL and \>200 mg/dL respectively) for at least 2 months prior to study entry. * immune modulatory agents including * In the last 3 months: * systemic steroids for more than 7 days. * daily treatment with multiple non-steroidal anti-inflammatory drugs (such as aspirin \>100mg/day, ibuprofen, naproxen, meloxicam, celecoxib) for more than 1 month within 3 months prior to study entry; * In the last 12 months: * azathioprine, 6-mercaptopurine, methotrexate, cyclosporin, anti-TNFα therapies (infliximab, adalimumab, etanercept) or anti-integrin therapies (namixilab) ; * more than 10 consecutive days oral or parenteral antibiotics within 4 weeks prior to study entry (Note: such subjects would not be included in the stool and PBMC analysis). * variable dose of antilipidemic agents (3-hydroxy-3-methyl-glutaryl (HMG)-Co-A reductase inhibitors - statins) in the 3 months prior to study entry. 15. The following laboratory abnormalities: * Neutrophil count ≤1.0 x 10\^9/L * Platelets \<100 x 10\^9/L * Hemoglobin \<10 g/dL * Albumin \<3.5 g/dL * International Normalized Ratio (INR) \>1.5 * Total bilirubin \>1.5 x upper limit of reference range (unless Gilbert's syndrome or extrahepatic source as denoted by increased indirect bilirubin fraction) * Either creatinine clearance ≤60 mL/minute calculated by Cockroft Gault or creatinine \>1.5x upper limit of reference range. 16. Known substance abuse, including inhaled or injected drugs in the year prior to Screening. 17. Cow milk allergy, lactose intolerance or any known or suspected hypersensitivity to study products.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome Measure | 24 Weeks | Incidence of adverse events per arm/group |
| Severity of Adverse Events | 24 weeks | Number of grade 3-5 adverse events |
| Adverse Events | 24 weeks | Number of patients with treatment-related adverse events |
| Percentage Fat Content of the Liver | baseline and 24 weeks | Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Serum Concentration (Cmin) | 0, 4, 12 and 24 Weeks | Minimum serum concentration (Cmin) of IMM-124E |
| Body Mass Index (BMI) | 24 Weeks | Change from Baseline of Body Mass Index (BMI) at 24 weeks |
| Waist Circumference | 24 Weeks | Change from Baseline of Waist Circumference at 24 weeks |
| Waist:Hip Ratio | 24 Weeks | Change from Baseline of Waist:Hip Ratio at 24 weeks |
| Hemoglobin (HB)A1C | 24 Weeks | Change from Baseline of Hemoglobin(HB)A1C at 24 weeks |
| Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | baseline and 24 Weeks | Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks |
| Total Cholesterol | 24 Weeks | Change from Baseline of Total Cholesterol at 24 weeks |
| Triglycerides | 24 Weeks | Change from Baseline of Triglycerides at 24 weeks |
| Low Density Lipoprotein (LDL) | 24 Weeks | Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks |
| High Density Lipoprotein (HDL) | 24 Weeks | Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks |
| Serum Aspartate Aminotransaminase (AST) | baseline to 24 Weeks | Mean change from Baseline of Serum AST |
| Bilirubin | baseline to 24 Weeks | Mean change from Baseline of Bilirubin |
| Albumin | baseline to 24 Weeks | Mean change from Baseline of Albumin |
| Gamma Glutamyl Transpeptidase (GGT) | baseline to 24 Weeks | Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT) |
| Systolic Blood Pressure | baseline and 24 weeks | Mean change in Systolic Blood Pressure |
| Pulse Rate | baseline and 24 weeks | Mean change in Pulse Rate from baseline to week 24 |
| Diastolic Blood Pressure | baseline and 24 weeks | Change in Diastolic Blood Pressure |
| Respiratory Rate | baseline and 24 weeks | Mean change in Respiratory Rate from baseline to week 24 |
| Serum Alanine Aminotransaminase (ALT) | baseline and 24 weeks | Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24 |
| Peak Serum Concentration (Cmax) | 0, 4, 12 and 24 Weeks | Peak serum concentration (Cmax) of IMM-124E |
| Area Under the Concentration Time Curve (AUC) | 0, 4, 12 and 24 Weeks | Area Under the Concentration Time Curve (AUC) of IMM-124E. Time points at which data were collected: baseline pre-dose, week 4, week 12 and week 24. |
| Elimination Half Life (T1/2) | 0, 4, 12 and 24 Weeks | Elimination Half Life (T1/2) of IMM-124E |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentrations of CK-18 Fragments | baseline to 24 weeks | The proportion of subjects with significant reduction of CK-18 (≥ 15%) between IMP 1200mg group to placebo. |
| Serum Concentrations of Human Adiponectin | 0 to 24 Weeks | Change from Run-in to Post-treatment in serum concentration of human Adiponectin. |
| Serum Concentrations of Cytokine IL-6 | 24 weeks | Mean Change from baseline to week 24 of serum concentration of cytokine IL-6 |
| Serum Concentration of Cytokine IL-12p70 | 24 weeks | Mean change from baseline to week 24 of Serum concentration of Cytokine IL-12p70 |
| Serum Concentration of Interferon Gamma (IFN-γ) | 24 weeks | Mean Change from baseline to week 24 of serum concentration of IFN-gamma |
| Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α) | 24 weeks | Mean Change from baseline to week 24 of serum concentration of TNF-α |
| Serum Concentration of Glucagon-like Peptide-1 (GLP-1) | 24 weeks | Mean Change from baseline to week 24 of serum concentration of GLP-1 |
| Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells | 0 and 24 Weeks | Change in percent of FoxP3+CD25-CD8+ cells in Peripheral Blood Mononuclear Cells |
| Serum Concentrations of C-Reactive Protein (CRP) | baseline to 24 Weeks | Mean Serum Concentrations of C-Reactive Protein (CRP) at week 24 |
| Serum Concentrations of Lipopolysaccharide (LPS) | 0, 4, 12 and 24 Weeks | The percentage of subjects reporting at least 15% reduction in LPS, from baseline to Week 24 |
| Serum Concentrations of LPS | baseline to 24 Weeks | Serum Concentrations of Lipopolysaccharide (LPS) (ng/mL) levels and change from Baseline |
| Gut Microbiome From Fecal Samples | 0, 4, 12 and 24 Weeks | Number of participants with measurable differences in gut microbiome constituents post-treatment |
| Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells | 0 and 24 Weeks | Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells |
Countries
Australia, Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm A IMM-124E, 600 mg three times daily, orally plus matching placebo
IMM-124E: IMM-124E | 43 |
| Treatment Arm B IMM-124E, 1200 mg three times daily, orally
IMM-124E: IMM-124E | 46 |
| Treatment Arm C Matching placebo, three times daily, orally
Placebo: Matched placebo | 44 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 0 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Non compliance | 3 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | TBC | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Treatment Arm C | Treatment Arm B | Treatment Arm A |
|---|---|---|---|---|
| Age, Continuous | 50.59 years STANDARD_DEVIATION 12.31 | 50.2 years STANDARD_DEVIATION 11.1 | 50.2 years STANDARD_DEVIATION 13.7 | 51.4 years STANDARD_DEVIATION 11.9 |
| Body Mass Index (BMI) | 34.21 kg/m^2 STANDARD_DEVIATION 5.653 | 34.54 kg/m^2 STANDARD_DEVIATION 5.678 | 34.12 kg/m^2 STANDARD_DEVIATION 5.802 | 33.97 kg/m^2 STANDARD_DEVIATION 5.439 |
| HbA1c | 6.141 % STANDARD_DEVIATION 0.896 | 6.12 % STANDARD_DEVIATION 0.916 | 6.16 % STANDARD_DEVIATION 0.999 | 6.14 % STANDARD_DEVIATION 0.765 |
| Hepatic Fat | 19.04 % STANDARD_DEVIATION 8.219 | 18.39 % STANDARD_DEVIATION 7.067 | 19.11 % STANDARD_DEVIATION 8.166 | 19.64 % STANDARD_DEVIATION 9.237 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 5 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 104 Participants | 34 Participants | 40 Participants | 30 Participants |
| Region of Enrollment Australia | 21 participants | 5 participants | 8 participants | 8 participants |
| Region of Enrollment Israel | 12 participants | 5 participants | 6 participants | 1 participants |
| Region of Enrollment United States | 100 participants | 34 participants | 32 participants | 34 participants |
| Sex: Female, Male Female | 70 Participants | 20 Participants | 27 Participants | 23 Participants |
| Sex: Female, Male Male | 63 Participants | 24 Participants | 19 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 46 | 1 / 44 |
| other Total, other adverse events | 39 / 43 | 41 / 46 | 38 / 44 |
| serious Total, serious adverse events | 1 / 43 | 2 / 46 | 3 / 44 |
Outcome results
Primary
Adverse Events
Number of patients with treatment-related adverse events
Time frame: 24 weeks
Population: Number of patients with any treatment-related AE
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IMM-124E, 600 mg | Adverse Events | 17 Participants |
| IMM-124E, 1200 mg | Adverse Events | 14 Participants |
| Matching Placebo | Adverse Events | 13 Participants |
Primary
Percentage Fat Content of the Liver
Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24
Time frame: baseline and 24 weeks
Population: The analysis population includes subjects with both baseline MRI and week 24 MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Percentage Fat Content of the Liver | -1.55 percentage of hepatic fat fraction | Standard Deviation 0.903 |
| IMM-124E, 1200 mg | Percentage Fat Content of the Liver | -0.90 percentage of hepatic fat fraction | Standard Deviation 0.818 |
| Matching Placebo | Percentage Fat Content of the Liver | -1.85 percentage of hepatic fat fraction | Standard Deviation 0.81 |
Primary
Safety Outcome Measure
Incidence of adverse events per arm/group
Time frame: 24 Weeks
Population: Number of treatment emerged AEs per arm/group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMM-124E, 600 mg | Safety Outcome Measure | 185 AEs |
| IMM-124E, 1200 mg | Safety Outcome Measure | 207 AEs |
| Matching Placebo | Safety Outcome Measure | 155 AEs |
Primary
Severity of Adverse Events
Number of grade 3-5 adverse events
Time frame: 24 weeks
Population: Number of grade 3-5 AEs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMM-124E, 600 mg | Severity of Adverse Events | 12 events |
| IMM-124E, 1200 mg | Severity of Adverse Events | 10 events |
| Matching Placebo | Severity of Adverse Events | 7 events |
Secondary
Albumin
Mean change from Baseline of Albumin
Time frame: baseline to 24 Weeks
Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Albumin | -0.8 g/dL | Standard Deviation 0.35 |
| IMM-124E, 1200 mg | Albumin | -0.2 g/dL | Standard Deviation 0.32 |
| Matching Placebo | Albumin | 0.3 g/dL | Standard Deviation 0.32 |
Secondary
Area Under the Concentration Time Curve (AUC)
Area Under the Concentration Time Curve (AUC) of IMM-124E. Time points at which data were collected: baseline pre-dose, week 4, week 12 and week 24.
Time frame: 0, 4, 12 and 24 Weeks
Population: The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Area Under the Concentration Time Curve (AUC) | 0 ng/mL | Standard Deviation 0 |
| IMM-124E, 1200 mg | Area Under the Concentration Time Curve (AUC) | 0 ng/mL | Standard Deviation 0 |
| Matching Placebo | Area Under the Concentration Time Curve (AUC) | 0 ng/mL | Standard Deviation 0 |
Secondary
Bilirubin
Mean change from Baseline of Bilirubin
Time frame: baseline to 24 Weeks
Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Bilirubin | -1.0 umol/l | Standard Deviation 3.56 |
| IMM-124E, 1200 mg | Bilirubin | -1.0 umol/l | Standard Deviation 0.54 |
| Matching Placebo | Bilirubin | 0.3 umol/l | Standard Deviation 0.53 |
Secondary
Body Mass Index (BMI)
Change from Baseline of Body Mass Index (BMI) at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Body Mass Index (BMI) | 0.20 kg/m^2 | Standard Deviation 1.024 |
| IMM-124E, 1200 mg | Body Mass Index (BMI) | -0.33 kg/m^2 | Standard Deviation 1.701 |
| Matching Placebo | Body Mass Index (BMI) | 0.09 kg/m^2 | Standard Deviation 1.35 |
Secondary
Diastolic Blood Pressure
Change in Diastolic Blood Pressure
Time frame: baseline and 24 weeks
Population: The analysis population include subjects with data of both baseline and week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Diastolic Blood Pressure | 0.6 mmHg | Standard Deviation 11.17 |
| IMM-124E, 1200 mg | Diastolic Blood Pressure | -0.5 mmHg | Standard Deviation 6.4 |
| Matching Placebo | Diastolic Blood Pressure | -0.3 mmHg | Standard Deviation 8.37 |
Secondary
Elimination Half Life (T1/2)
Elimination Half Life (T1/2) of IMM-124E
Time frame: 0, 4, 12 and 24 Weeks
Population: The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Elimination Half Life (T1/2) | 0 seconds | Standard Deviation 0 |
| IMM-124E, 1200 mg | Elimination Half Life (T1/2) | 0 seconds | Standard Deviation 0 |
| Matching Placebo | Elimination Half Life (T1/2) | 0 seconds | Standard Deviation 0 |
Secondary
Gamma Glutamyl Transpeptidase (GGT)
Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT)
Time frame: baseline to 24 Weeks
Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Gamma Glutamyl Transpeptidase (GGT) | -7.1 U/L | Standard Deviation 5.03 |
| IMM-124E, 1200 mg | Gamma Glutamyl Transpeptidase (GGT) | -9.7 U/L | Standard Deviation 4.62 |
| Matching Placebo | Gamma Glutamyl Transpeptidase (GGT) | -5.7 U/L | Standard Deviation 4.56 |
Secondary
Hemoglobin (HB)A1C
Change from Baseline of Hemoglobin(HB)A1C at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Hemoglobin (HB)A1C | 1.0 percentage | Standard Deviation 0.88 |
| IMM-124E, 1200 mg | Hemoglobin (HB)A1C | 0.1 percentage | Standard Deviation 0.84 |
| Matching Placebo | Hemoglobin (HB)A1C | 0.2 percentage | Standard Deviation 0.81 |
Secondary
High Density Lipoprotein (HDL)
Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | High Density Lipoprotein (HDL) | 0.0 mmol/l | Standard Deviation 0.03 |
| IMM-124E, 1200 mg | High Density Lipoprotein (HDL) | 0.0 mmol/l | Standard Deviation 0.02 |
| Matching Placebo | High Density Lipoprotein (HDL) | 0.1 mmol/l | Standard Deviation 0.02 |
Secondary
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks
Time frame: baseline and 24 Weeks
Population: HOMA-IR is calculated according to the formula: fasting insulin (mU/mL) x fasting glucose (mmol/L)/22.5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 2.098 no unit | Standard Deviation 2.3374 |
| IMM-124E, 1200 mg | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 0.057 no unit | Standard Deviation 2.134 |
| Matching Placebo | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 0.655 no unit | Standard Deviation 2.1648 |
Secondary
Low Density Lipoprotein (LDL)
Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Low Density Lipoprotein (LDL) | -0.1 mmol/l | Standard Deviation 0.09 |
| IMM-124E, 1200 mg | Low Density Lipoprotein (LDL) | 0.1 mmol/l | Standard Deviation 0.08 |
| Matching Placebo | Low Density Lipoprotein (LDL) | 0.0 mmol/l | Standard Deviation 0.08 |
Secondary
Minimum Serum Concentration (Cmin)
Minimum serum concentration (Cmin) of IMM-124E
Time frame: 0, 4, 12 and 24 Weeks
Population: The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Minimum Serum Concentration (Cmin) | 0 ng/mL | Standard Deviation 0 |
| IMM-124E, 1200 mg | Minimum Serum Concentration (Cmin) | 0 ng/mL | Standard Deviation 0 |
| Matching Placebo | Minimum Serum Concentration (Cmin) | 0 ng/mL | Standard Deviation 0 |
Secondary
Peak Serum Concentration (Cmax)
Peak serum concentration (Cmax) of IMM-124E
Time frame: 0, 4, 12 and 24 Weeks
Population: The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Peak Serum Concentration (Cmax) | 0 ng/mL | Standard Deviation 0 |
| IMM-124E, 1200 mg | Peak Serum Concentration (Cmax) | 0 ng/mL | Standard Deviation 0 |
| Matching Placebo | Peak Serum Concentration (Cmax) | 0 ng/mL | Standard Deviation 0 |
Secondary
Pulse Rate
Mean change in Pulse Rate from baseline to week 24
Time frame: baseline and 24 weeks
Population: The analysis population include subjects with Pulse Rate data of both baseline and week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Pulse Rate | -0.8 beats/minute | Standard Deviation 10.91 |
| IMM-124E, 1200 mg | Pulse Rate | -1.9 beats/minute | Standard Deviation 9.29 |
| Matching Placebo | Pulse Rate | 2.1 beats/minute | Standard Deviation 10 |
Secondary
Respiratory Rate
Mean change in Respiratory Rate from baseline to week 24
Time frame: baseline and 24 weeks
Population: The analysis population includes subjects with both respiratory rate data at baseline and week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Respiratory Rate | -0.2 breaths/minute | Standard Deviation 1.63 |
| IMM-124E, 1200 mg | Respiratory Rate | -0.3 breaths/minute | Standard Deviation 1.68 |
| Matching Placebo | Respiratory Rate | 0.1 breaths/minute | Standard Deviation 2.08 |
Secondary
Serum Alanine Aminotransaminase (ALT)
Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Alanine Aminotransaminase (ALT) | -14.4 IU/L | Standard Deviation 4.95 |
| IMM-124E, 1200 mg | Serum Alanine Aminotransaminase (ALT) | -10.7 IU/L | Standard Deviation 4.55 |
| Matching Placebo | Serum Alanine Aminotransaminase (ALT) | -10.3 IU/L | Standard Deviation 4.49 |
Secondary
Serum Alanine Aminotransaminase (ALT)
Number of patients with ALT within the normal reference range at Week 24 (defined a \<19 IU/L for women and \<30 IU/L for men)
Time frame: 24 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IMM-124E, 600 mg | Serum Alanine Aminotransaminase (ALT) | 3 Participants |
| IMM-124E, 1200 mg | Serum Alanine Aminotransaminase (ALT) | 4 Participants |
| Matching Placebo | Serum Alanine Aminotransaminase (ALT) | 2 Participants |
Secondary
Serum Alanine Aminotransaminase (ALT)
Mean change from Baseline of serum ALT
Time frame: baseline to 24 weeks
Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Alanine Aminotransaminase (ALT) | -14.4 IU/L | Standard Deviation 4.95 |
| IMM-124E, 1200 mg | Serum Alanine Aminotransaminase (ALT) | -10.7 IU/L | Standard Deviation 4.55 |
| Matching Placebo | Serum Alanine Aminotransaminase (ALT) | -10.3 IU/L | Standard Deviation 4.49 |
Secondary
Serum Aspartate Aminotransaminase (AST)
Mean change from Baseline of Serum AST
Time frame: baseline to 24 Weeks
Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Aspartate Aminotransaminase (AST) | -7.8 IU/L | Standard Deviation 3.32 |
| IMM-124E, 1200 mg | Serum Aspartate Aminotransaminase (AST) | -7.4 IU/L | Standard Deviation 3.05 |
| Matching Placebo | Serum Aspartate Aminotransaminase (AST) | -7.5 IU/L | Standard Deviation 3.01 |
Secondary
Systolic Blood Pressure
Mean change in Systolic Blood Pressure
Time frame: baseline and 24 weeks
Population: The analysis population include subjects with data of both baseline and week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Systolic Blood Pressure | 6.1 mmHg | Standard Deviation 16.19 |
| IMM-124E, 1200 mg | Systolic Blood Pressure | 2.0 mmHg | Standard Deviation 12.73 |
| Matching Placebo | Systolic Blood Pressure | 0.2 mmHg | Standard Deviation 14.75 |
Secondary
Total Cholesterol
Change from Baseline of Total Cholesterol at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Total Cholesterol | -0.1 mmol/l | Standard Deviation 0.11 |
| IMM-124E, 1200 mg | Total Cholesterol | 0.0 mmol/l | Standard Deviation 0.1 |
| Matching Placebo | Total Cholesterol | 0.0 mmol/l | Standard Deviation 0.1 |
Secondary
Triglycerides
Change from Baseline of Triglycerides at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Triglycerides | -0.7 mmol/l | Standard Deviation 1.25 |
| IMM-124E, 1200 mg | Triglycerides | -0.3 mmol/l | Standard Deviation 1.15 |
| Matching Placebo | Triglycerides | -0.4 mmol/l | Standard Deviation 1.14 |
Secondary
Waist Circumference
Change from Baseline of Waist Circumference at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Waist Circumference | -1.20 cm | Standard Deviation 4.353 |
| IMM-124E, 1200 mg | Waist Circumference | -0.35 cm | Standard Deviation 5.969 |
| Matching Placebo | Waist Circumference | -0.92 cm | Standard Deviation 6.09 |
Secondary
Waist:Hip Ratio
Change from Baseline of Waist:Hip Ratio at 24 weeks
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Waist:Hip Ratio | -0.02 ratio | Standard Deviation 0.051 |
| IMM-124E, 1200 mg | Waist:Hip Ratio | 0.01 ratio | Standard Deviation 0.063 |
| Matching Placebo | Waist:Hip Ratio | 0.01 ratio | Standard Deviation 0.079 |
Other Pre-specified
Gut Microbiome From Fecal Samples
Number of participants with measurable differences in gut microbiome constituents post-treatment
Time frame: 0, 4, 12 and 24 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IMM-124E, 600 mg | Gut Microbiome From Fecal Samples | 0 Participants |
| IMM-124E, 1200 mg | Gut Microbiome From Fecal Samples | 0 Participants |
| Matching Placebo | Gut Microbiome From Fecal Samples | 0 Participants |
Other Pre-specified
Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells
Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells
Time frame: 0 and 24 Weeks
Population: Sub group population with PBMC FACS data, selected sites only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells | NA percentage of cells | — |
| IMM-124E, 1200 mg | Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells | 0.46 percentage of cells | Standard Deviation 0.26 |
| Matching Placebo | Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells | 14.59 percentage of cells | Standard Deviation 14.58 |
Other Pre-specified
Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells
Change in percent of FoxP3+CD25-CD8+ cells in Peripheral Blood Mononuclear Cells
Time frame: 0 and 24 Weeks
Population: Sub group population with PBMC FACS data, selected sites only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells | NA percentage of cells | — |
| IMM-124E, 1200 mg | Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells | -0.01 percentage of cells | Standard Deviation 0.33 |
| Matching Placebo | Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells | 12.52 percentage of cells | Standard Deviation 12.32 |
Other Pre-specified
Serum Concentration of Cytokine IL-12p70
Mean change from baseline to week 24 of Serum concentration of Cytokine IL-12p70
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentration of Cytokine IL-12p70 | 0.0494 pg/mL | Standard Deviation 1.0006 |
| IMM-124E, 1200 mg | Serum Concentration of Cytokine IL-12p70 | 0.3274 pg/mL | Standard Deviation 2.76062 |
| Matching Placebo | Serum Concentration of Cytokine IL-12p70 | 0.0579 pg/mL | Standard Deviation 1.35852 |
Other Pre-specified
Serum Concentration of Glucagon-like Peptide-1 (GLP-1)
Mean Change from baseline to week 24 of serum concentration of GLP-1
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentration of Glucagon-like Peptide-1 (GLP-1) | 1.6457 pM | Standard Deviation 15.79917 |
| IMM-124E, 1200 mg | Serum Concentration of Glucagon-like Peptide-1 (GLP-1) | -1.5310 pM | Standard Deviation 13.07262 |
| Matching Placebo | Serum Concentration of Glucagon-like Peptide-1 (GLP-1) | 3.4820 pM | Standard Deviation 33.36977 |
Other Pre-specified
Serum Concentration of Interferon Gamma (IFN-γ)
Mean Change from baseline to week 24 of serum concentration of IFN-gamma
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentration of Interferon Gamma (IFN-γ) | 0.9523 pg/mL | Standard Deviation 6.25581 |
| IMM-124E, 1200 mg | Serum Concentration of Interferon Gamma (IFN-γ) | 0.8058 pg/mL | Standard Deviation 6.59164 |
| Matching Placebo | Serum Concentration of Interferon Gamma (IFN-γ) | 1.4514 pg/mL | Standard Deviation 7.56336 |
Other Pre-specified
Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α)
Mean Change from baseline to week 24 of serum concentration of TNF-α
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α) | -0.1691 pg/mL | Standard Deviation 1.68068 |
| IMM-124E, 1200 mg | Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α) | -0.5082 pg/mL | Standard Deviation 1.59892 |
| Matching Placebo | Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α) | -0.3877 pg/mL | Standard Deviation 2.16469 |
Other Pre-specified
Serum Concentrations of CK-18 Fragments
The proportion of subjects with significant reduction of CK-18 (≥ 15%) between IMP 1200mg group to placebo.
Time frame: baseline to 24 weeks
Population: FAS population, excluding outlier sites. this Outcome Measure was pre-specified to be assessed in the 1200mg and Placebo Arms/Groups \*only\*
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IMM-124E, 1200 mg | Serum Concentrations of CK-18 Fragments | 14 Participants |
| Matching Placebo | Serum Concentrations of CK-18 Fragments | 6 Participants |
Other Pre-specified
Serum Concentrations of C-Reactive Protein (CRP)
Mean Serum Concentrations of C-Reactive Protein (CRP) at week 24
Time frame: baseline to 24 Weeks
Population: assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentrations of C-Reactive Protein (CRP) | 0.711 mg/L | Standard Deviation 0.68 |
| IMM-124E, 1200 mg | Serum Concentrations of C-Reactive Protein (CRP) | 1.129 mg/L | Standard Deviation 1.637 |
| Matching Placebo | Serum Concentrations of C-Reactive Protein (CRP) | 1.364 mg/L | Standard Deviation 2.317 |
Other Pre-specified
Serum Concentrations of Cytokine IL-6
Mean Change from baseline to week 24 of serum concentration of cytokine IL-6
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentrations of Cytokine IL-6 | 0.1234 pg/mL | Standard Deviation 0.90505 |
| IMM-124E, 1200 mg | Serum Concentrations of Cytokine IL-6 | 0.1031 pg/mL | Standard Deviation 1.63948 |
| Matching Placebo | Serum Concentrations of Cytokine IL-6 | 0.4117 pg/mL | Standard Deviation 1.50248 |
Other Pre-specified
Serum Concentrations of Human Adiponectin
Change from Run-in to Post-treatment in serum concentration of human Adiponectin.
Time frame: 0 to 24 Weeks
Population: ITT population. Run-in = mean of screening and baseline values. assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentrations of Human Adiponectin | 107560.15 pg/mL | Standard Deviation 1082735 |
| IMM-124E, 1200 mg | Serum Concentrations of Human Adiponectin | 208185.48 pg/mL | Standard Deviation 1115352.8 |
| Matching Placebo | Serum Concentrations of Human Adiponectin | 1082735.0 pg/mL | Standard Deviation 1900710.5 |
Other Pre-specified
Serum Concentrations of Lipopolysaccharide (LPS)
The percentage of subjects reporting at least 15% reduction in LPS, from baseline to Week 24
Time frame: 0, 4, 12 and 24 Weeks
Population: excluding subjects with \< 250 LPS at baseline (comparing 1200mg IMP group to Placebo group). PP population, excluding outliers sites. this Outcome Measure was pre-specified to be assessed in the 1200mg and Placebo Arms/Groups \*only\*
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IMM-124E, 1200 mg | Serum Concentrations of Lipopolysaccharide (LPS) | 18 Participants |
| Matching Placebo | Serum Concentrations of Lipopolysaccharide (LPS) | 10 Participants |
Other Pre-specified
Serum Concentrations of LPS
Serum Concentrations of Lipopolysaccharide (LPS) (ng/mL) levels and change from Baseline
Time frame: baseline to 24 Weeks
Population: assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E, 600 mg | Serum Concentrations of LPS | -130.763 ng/mL | Standard Deviation 188.153 |
| IMM-124E, 1200 mg | Serum Concentrations of LPS | 78.488 ng/mL | Standard Deviation 173.029 |
| Matching Placebo | Serum Concentrations of LPS | 414.912 ng/mL | Standard Deviation 182.632 |