Trial Outcomes & Findings for A Phase ll Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis (NCT NCT02316717)

Results Overview

Incidence of adverse events per arm/group

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

133 participants

Primary outcome timeframe

24 Weeks

Results posted on

2020-02-21

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Arm A IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E	Treatment Arm B IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E	Treatment Arm C Matching placebo, three times daily, orally Placebo: Matched placebo
Overall Study STARTED	43	46	44
Overall Study COMPLETED	32	39	41
Overall Study NOT COMPLETED	11	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Arm A IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E	Treatment Arm B IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E	Treatment Arm C Matching placebo, three times daily, orally Placebo: Matched placebo
Overall Study Adverse Event	2	2	0
Overall Study Lost to Follow-up	1	2	1
Overall Study Non compliance	3	1	0
Overall Study Protocol Violation	2	0	0
Overall Study Withdrawal by Subject	2	1	1
Overall Study Death	0	0	1
Overall Study Physician Decision	0	1	0
Overall Study TBC	1	0	0

Baseline Characteristics

A Phase ll Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm A n=43 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E	Treatment Arm B n=46 Participants IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E	Treatment Arm C n=44 Participants Matching placebo, three times daily, orally Placebo: Matched placebo	Total n=133 Participants Total of all reporting groups
Age, Continuous	51.4 years STANDARD_DEVIATION 11.9 • n=5 Participants	50.2 years STANDARD_DEVIATION 13.7 • n=7 Participants	50.2 years STANDARD_DEVIATION 11.1 • n=5 Participants	50.59 years STANDARD_DEVIATION 12.31 • n=4 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	27 Participants n=7 Participants	20 Participants n=5 Participants	70 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	19 Participants n=7 Participants	24 Participants n=5 Participants	63 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	40 Participants n=7 Participants	34 Participants n=5 Participants	104 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment United States	34 participants n=5 Participants	32 participants n=7 Participants	34 participants n=5 Participants	100 participants n=4 Participants
Region of Enrollment Israel	1 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	12 participants n=4 Participants
Region of Enrollment Australia	8 participants n=5 Participants	8 participants n=7 Participants	5 participants n=5 Participants	21 participants n=4 Participants
Body Mass Index (BMI)	33.97 kg/m^2 STANDARD_DEVIATION 5.439 • n=5 Participants	34.12 kg/m^2 STANDARD_DEVIATION 5.802 • n=7 Participants	34.54 kg/m^2 STANDARD_DEVIATION 5.678 • n=5 Participants	34.21 kg/m^2 STANDARD_DEVIATION 5.653 • n=4 Participants
HbA1c	6.14 % STANDARD_DEVIATION 0.765 • n=5 Participants	6.16 % STANDARD_DEVIATION 0.999 • n=7 Participants	6.12 % STANDARD_DEVIATION 0.916 • n=5 Participants	6.141 % STANDARD_DEVIATION 0.896 • n=4 Participants
Hepatic Fat	19.64 % STANDARD_DEVIATION 9.237 • n=5 Participants	19.11 % STANDARD_DEVIATION 8.166 • n=7 Participants	18.39 % STANDARD_DEVIATION 7.067 • n=5 Participants	19.04 % STANDARD_DEVIATION 8.219 • n=4 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: Number of treatment emerged AEs per arm/group

Incidence of adverse events per arm/group

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=43 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=46 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=44 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Safety Outcome Measure	185 AEs	207 AEs	155 AEs

PRIMARY outcome

Timeframe: baseline and 24 weeks

Population: The analysis population includes subjects with both baseline MRI and week 24 MRI.

Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=35 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=40 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=41 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Percentage Fat Content of the Liver	-1.55 percentage of hepatic fat fraction Standard Deviation 0.903	-0.90 percentage of hepatic fat fraction Standard Deviation 0.818	-1.85 percentage of hepatic fat fraction Standard Deviation 0.810

PRIMARY outcome

Timeframe: 24 weeks

Population: Number of patients with any treatment-related AE

Number of patients with treatment-related adverse events

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=43 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=46 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=44 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Adverse Events	17 Participants	14 Participants	13 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Number of grade 3-5 AEs

Number of grade 3-5 adverse events

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=43 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=46 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=44 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Severity of Adverse Events	12 events	10 events	7 events

SECONDARY outcome

Timeframe: baseline and 24 weeks

Population: The analysis population include subjects with data of both baseline and week 24

Mean change in Systolic Blood Pressure

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=41 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Systolic Blood Pressure	6.1 mmHg Standard Deviation 16.19	2.0 mmHg Standard Deviation 12.73	0.2 mmHg Standard Deviation 14.75

SECONDARY outcome

Timeframe: baseline and 24 weeks

Population: The analysis population include subjects with Pulse Rate data of both baseline and week 24

Mean change in Pulse Rate from baseline to week 24

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=41 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Pulse Rate	-0.8 beats/minute Standard Deviation 10.91	-1.9 beats/minute Standard Deviation 9.29	2.1 beats/minute Standard Deviation 10.00

SECONDARY outcome

Timeframe: baseline and 24 weeks

Population: The analysis population include subjects with data of both baseline and week 24

Change in Diastolic Blood Pressure

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=41 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Diastolic Blood Pressure	0.6 mmHg Standard Deviation 11.17	-0.5 mmHg Standard Deviation 6.40	-0.3 mmHg Standard Deviation 8.37

SECONDARY outcome

Timeframe: baseline and 24 weeks

Population: The analysis population includes subjects with both respiratory rate data at baseline and week 24

Mean change in Respiratory Rate from baseline to week 24

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=41 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Respiratory Rate	-0.2 breaths/minute Standard Deviation 1.63	-0.3 breaths/minute Standard Deviation 1.68	0.1 breaths/minute Standard Deviation 2.08

SECONDARY outcome

Timeframe: baseline and 24 weeks

Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Alanine Aminotransaminase (ALT)	-14.4 IU/L Standard Deviation 4.95	-10.7 IU/L Standard Deviation 4.55	-10.3 IU/L Standard Deviation 4.49

SECONDARY outcome

Timeframe: 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.

Peak serum concentration (Cmax) of IMM-124E

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Peak Serum Concentration (Cmax)	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0

SECONDARY outcome

Timeframe: 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.

Minimum serum concentration (Cmin) of IMM-124E

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Minimum Serum Concentration (Cmin)	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Area Under the Concentration Time Curve (AUC)	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0

SECONDARY outcome

Timeframe: 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.

Elimination Half Life (T1/2) of IMM-124E

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Elimination Half Life (T1/2)	0 seconds Standard Deviation 0	0 seconds Standard Deviation 0	0 seconds Standard Deviation 0

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Body Mass Index (BMI) at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Body Mass Index (BMI)	0.20 kg/m^2 Standard Deviation 1.024	-0.33 kg/m^2 Standard Deviation 1.701	0.09 kg/m^2 Standard Deviation 1.350

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Waist Circumference at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=21 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=33 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=29 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Waist Circumference	-1.20 cm Standard Deviation 4.353	-0.35 cm Standard Deviation 5.969	-0.92 cm Standard Deviation 6.090

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Waist:Hip Ratio at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=21 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=33 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=29 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Waist:Hip Ratio	-0.02 ratio Standard Deviation 0.051	0.01 ratio Standard Deviation 0.063	0.01 ratio Standard Deviation 0.079

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Hemoglobin(HB)A1C at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=36 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=39 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Hemoglobin (HB)A1C	1.0 percentage Standard Deviation 0.88	0.1 percentage Standard Deviation 0.84	0.2 percentage Standard Deviation 0.81

SECONDARY outcome

Timeframe: baseline and 24 Weeks

Population: HOMA-IR is calculated according to the formula: fasting insulin (mU/mL) x fasting glucose (mmol/L)/22.5

Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=30 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=36 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=35 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	2.098 no unit Standard Deviation 2.3374	0.057 no unit Standard Deviation 2.1340	0.655 no unit Standard Deviation 2.1648

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Total Cholesterol at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Total Cholesterol	-0.1 mmol/l Standard Deviation 0.11	0.0 mmol/l Standard Deviation 0.10	0.0 mmol/l Standard Deviation 0.10

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Triglycerides at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Triglycerides	-0.7 mmol/l Standard Deviation 1.25	-0.3 mmol/l Standard Deviation 1.15	-0.4 mmol/l Standard Deviation 1.14

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=30 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=37 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=37 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Low Density Lipoprotein (LDL)	-0.1 mmol/l Standard Deviation 0.09	0.1 mmol/l Standard Deviation 0.08	0.0 mmol/l Standard Deviation 0.08

SECONDARY outcome

Timeframe: 24 Weeks

Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
High Density Lipoprotein (HDL)	0.0 mmol/l Standard Deviation 0.03	0.0 mmol/l Standard Deviation 0.02	0.1 mmol/l Standard Deviation 0.02

SECONDARY outcome

Timeframe: baseline to 24 weeks

Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Mean change from Baseline of serum ALT

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Alanine Aminotransaminase (ALT)	-14.4 IU/L Standard Deviation 4.95	-10.7 IU/L Standard Deviation 4.55	-10.3 IU/L Standard Deviation 4.49

SECONDARY outcome

Timeframe: baseline to 24 Weeks

Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Mean change from Baseline of Serum AST

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Aspartate Aminotransaminase (AST)	-7.8 IU/L Standard Deviation 3.32	-7.4 IU/L Standard Deviation 3.05	-7.5 IU/L Standard Deviation 3.01

SECONDARY outcome

Timeframe: baseline to 24 Weeks

Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Mean change from Baseline of Bilirubin

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Bilirubin	-1.0 umol/l Standard Deviation 3.56	-1.0 umol/l Standard Deviation 0.54	0.3 umol/l Standard Deviation 0.53

SECONDARY outcome

Timeframe: baseline to 24 Weeks

Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Mean change from Baseline of Albumin

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Albumin	-0.8 g/dL Standard Deviation 0.35	-0.2 g/dL Standard Deviation 0.32	0.3 g/dL Standard Deviation 0.32

SECONDARY outcome

Timeframe: baseline to 24 Weeks

Population: assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT)

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Gamma Glutamyl Transpeptidase (GGT)	-7.1 U/L Standard Deviation 5.03	-9.7 U/L Standard Deviation 4.62	-5.7 U/L Standard Deviation 4.56

SECONDARY outcome

Timeframe: 24 Weeks

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)

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=40 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Alanine Aminotransaminase (ALT)	3 Participants	4 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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\*

The percentage of subjects reporting at least 15% reduction in LPS, from baseline to Week 24

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=28 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=29 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentrations of Lipopolysaccharide (LPS)	—	18 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 and 24 Weeks

Population: Sub group population with PBMC FACS data, selected sites only.

Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=1 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=8 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=3 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells	NA percentage of cells Standard Deviation NA only 1 participant's data analyzed in 600mg arm.	0.46 percentage of cells Standard Deviation 0.26	14.59 percentage of cells Standard Deviation 14.58

OTHER_PRE_SPECIFIED outcome

Timeframe: 0, 4, 12 and 24 Weeks

Number of participants with measurable differences in gut microbiome constituents post-treatment

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=4 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=12 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=5 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Gut Microbiome From Fecal Samples	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 24 Weeks

Population: assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported

Serum Concentrations of Lipopolysaccharide (LPS) (ng/mL) levels and change from Baseline

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=33 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=39 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=35 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentrations of LPS	-130.763 ng/mL Standard Deviation 188.153	78.488 ng/mL Standard Deviation 173.029	414.912 ng/mL Standard Deviation 182.632

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 24 Weeks

Population: assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported

Mean Serum Concentrations of C-Reactive Protein (CRP) at week 24

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=35 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=40 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=41 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentrations of C-Reactive Protein (CRP)	0.711 mg/L Standard Deviation 0.68	1.129 mg/L Standard Deviation 1.637	1.364 mg/L Standard Deviation 2.317

OTHER_PRE_SPECIFIED outcome

Timeframe: 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\*

The proportion of subjects with significant reduction of CK-18 (≥ 15%) between IMP 1200mg group to placebo.

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=36 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=33 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentrations of CK-18 Fragments	—	14 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Change from Run-in to Post-treatment in serum concentration of human Adiponectin.

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=38 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=43 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=37 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentrations of Human Adiponectin	107560.15 pg/mL Standard Deviation 1082735.0	208185.48 pg/mL Standard Deviation 1115352.8	1082735.0 pg/mL Standard Deviation 1900710.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: ITT population

Mean Change from baseline to week 24 of serum concentration of cytokine IL-6

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=36 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=41 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=39 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentrations of Cytokine IL-6	0.1234 pg/mL Standard Deviation 0.90505	0.1031 pg/mL Standard Deviation 1.63948	0.4117 pg/mL Standard Deviation 1.50248

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: ITT population

Mean change from baseline to week 24 of Serum concentration of Cytokine IL-12p70

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=36 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=41 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=39 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentration of Cytokine IL-12p70	0.0494 pg/mL Standard Deviation 1.00060	0.3274 pg/mL Standard Deviation 2.76062	0.0579 pg/mL Standard Deviation 1.35852

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: ITT population

Mean Change from baseline to week 24 of serum concentration of IFN-gamma

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=36 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=41 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=39 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentration of Interferon Gamma (IFN-γ)	0.9523 pg/mL Standard Deviation 6.25581	0.8058 pg/mL Standard Deviation 6.59164	1.4514 pg/mL Standard Deviation 7.56336

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: ITT population

Mean Change from baseline to week 24 of serum concentration of TNF-α

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=36 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=41 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=39 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α)	-0.1691 pg/mL Standard Deviation 1.68068	-0.5082 pg/mL Standard Deviation 1.59892	-0.3877 pg/mL Standard Deviation 2.16469

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: ITT population

Mean Change from baseline to week 24 of serum concentration of GLP-1

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=37 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=41 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=39 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Serum Concentration of Glucagon-like Peptide-1 (GLP-1)	1.6457 pM Standard Deviation 15.79917	-1.5310 pM Standard Deviation 13.07262	3.4820 pM Standard Deviation 33.36977

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 and 24 Weeks

Population: Sub group population with PBMC FACS data, selected sites only.

Change in percent of FoxP3+CD25-CD8+ cells in Peripheral Blood Mononuclear Cells

Outcome measures

Outcome measures
Measure	IMM-124E, 600 mg n=1 Participants IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=8 Participants IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=3 Participants Matching placebo, three times daily, orally 24 weeks of treatment
Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells	NA percentage of cells Standard Deviation NA only 1 participant's data analyzed in 600mg arm.	-0.01 percentage of cells Standard Deviation 0.33	12.52 percentage of cells Standard Deviation 12.32

Adverse Events

IMM-124E, 600 mg

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

IMM-124E, 1200 mg

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Matching Placebo

Serious events: 3 serious events

Other events: 38 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	IMM-124E, 600 mg n=43 participants at risk IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	IMM-124E, 1200 mg n=46 participants at risk IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	Matching Placebo n=44 participants at risk Matching placebo, three times daily, orally 24 weeks of treatment
General disorders Chest Pain	0.00% 0/43 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	2.2% 1/46 • Number of events 1 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/44 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/43 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/46 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	2.3% 1/44 • Number of events 1 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.
Investigations Blood creatine phosphokinase increased	0.00% 0/43 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/46 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	2.3% 1/44 • Number of events 1 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	2.3% 1/43 • Number of events 1 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/46 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/44 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.
Product Issues Anxiety	0.00% 0/43 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	2.2% 1/46 • Number of events 1 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/44 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.
Surgical and medical procedures Hospitalisation	0.00% 0/43 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	0.00% 0/46 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.	2.3% 1/44 • Number of events 1 • 28 weeks after participant received first dose The adverse event information collected in the clinical study is collected based on the adverse event definition of ''Results Data Element Definitions for Adverse Events''. The adverse events data was collected based on physician's assessments, laboratory assessments, subjects reporting and questionnaires.

Other adverse events

Additional Information

Neta Tobis, Clinical Director

Immuron

Phone: +972549277334

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place