Trial Outcomes & Findings for Use of a Novel Drug in People With Non-alcoholic Steatohepatitis (NASH) or Non-alcoholic Fatty Liver Disease (NAFLD) (NCT NCT02605616)

NCT ID: NCT02605616

Last Updated: 2024-03-01

Results Overview

Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of \<5% is used to distinguish between normal and fatty liver.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 93 participants
• Primary outcome timeframe: baseline, approximately 12 weeks
• Results posted on: 2024-03-01

Participant Flow

Participant milestones

Measure	Active Drug AZ Compound AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Overall Study STARTED	46	47
Overall Study COMPLETED	42	43
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Use of a Novel Drug in People With Non-alcoholic Steatohepatitis (NASH) or Non-alcoholic Fatty Liver Disease (NAFLD)

Baseline characteristics by cohort

Measure	Active Drug AZ Compound n=46 Participants AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo n=47 Participants Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Total n=93 Participants Total of all reporting groups
Age, Continuous	53.7 years STANDARD_DEVIATION 11.7 • n=5 Participants	53.3 years STANDARD_DEVIATION 11.4 • n=7 Participants	53.7 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	43 Participants n=7 Participants	88 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	45 Participants n=7 Participants	88 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	46 participants n=5 Participants	47 participants n=7 Participants	93 participants n=5 Participants
Number of baseline particpants	46 Participants n=5 Participants	47 Participants n=7 Participants	93 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, approximately 12 weeks

Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of <5% is used to distinguish between normal and fatty liver.

Outcome measures

Measure	Active Drug AZ Compound n=42 Participants AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo n=43 Participants Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Percentage Change in Hepatic Fat	-0.667 Percentage change in liver fat fraction Standard Deviation 5.246	0.139 Percentage change in liver fat fraction Standard Deviation 4.323

PRIMARY outcome

Timeframe: baseline, approximately 12 weeks

Hepatic conversion of [13C] cortisone to [13C] cortisol was assessed before and after the treatment in both groups using the triple tracer cortisol test.

Outcome measures

Measure	Active Drug AZ Compound n=42 Participants AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo n=43 Participants Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Number of Participants With no Conversion of [13C] Cortisone to [13C] Cortisol	42 Participants	0 Participants

SECONDARY outcome

Timeframe: baseline, approximately 12 weeks

Liver fibrosis will be measured with Magnetic Resonance Enterography (MRE) at baseline and then compared after ~12 weeks of treatment. A clinical cut-off of 2.93 kPa was used to classify the results as either normal or elevated liver stiffness. Change in Liver fibrosis (kPa) is compared in between the groups.

Outcome measures

Measure	Active Drug AZ Compound n=42 Participants AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo n=43 Participants Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Liver Fibrosis Measured With MRE in kPa	-0.639 kPa Standard Deviation 0.991	-0.662 kPa Standard Deviation 0.977

SECONDARY outcome

Timeframe: baseline, approximately 12 weeks

Population: Insulin Sensitivity was measured in the participants that completed the oral glucose tolerance test .

Total insulin sensitivity (Si) and hepatic insulin sensitivity (Si liver) will be measured with an Oral glucose Tolerance test at baseline and after ~12 weeks of treatment.

Outcome measures

Measure	Active Drug AZ Compound n=29 Participants AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo n=32 Participants Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver) Change in SI	-0.225 10^-4 dl/kg/min per uU/ml Standard Deviation 1.918	0.719 10^-4 dl/kg/min per uU/ml Standard Deviation 3.361
Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver) Change in Si liver	0.075 10^-4 dl/kg/min per uU/ml Standard Deviation 1.948	0.126 10^-4 dl/kg/min per uU/ml Standard Deviation 2.369

Adverse Events

Active Drug AZ Compound

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Active Drug AZ Compound n=46 participants at risk AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).	Placebo n=47 participants at risk Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).
General disorders Headache	17.4% 8/46 • 3 months	8.5% 4/47 • 3 months
Gastrointestinal disorders Diarrhea	19.6% 9/46 • 3 months	12.8% 6/47 • 3 months
Endocrine disorders Increased TSH	6.5% 3/46 • 3 months	0.00% 0/47 • 3 months

Additional Information

Dr. Rita Basu

University of Virginia

Phone: 434-924-5183

Email: rb4vd@virginia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place