Trial Outcomes & Findings for Gemcabene for the Treatment of Pediatric NAFLD (NCT NCT03436420)

NCT ID: NCT03436420

Last Updated: 2020-12-31

Results Overview

Percent change in alanine aminotransferase (ALT) from baseline to 12 weeks was examined. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 units/Liter (U/L) for boys and girls aged 1-18. Children with a sustained ALT ≥ 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2020-12-31

Participant Flow

Children were recruited from the patient population of Children's Healthcare of Atlanta, in Atlanta, Georgia. Enrollment began on March 29, 2018 and study follow up was completed on August 27, 2019.

Participant milestones

Measure	Gemcabene Children with nonalcoholic fatty liver disease (NAFLD) receiving 12 weeks of treatment with gemcabene
Overall Study STARTED	6
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Gemcabene Children with nonalcoholic fatty liver disease (NAFLD) receiving 12 weeks of treatment with gemcabene
Overall Study Lack of Efficacy	3

Baseline Characteristics

Gemcabene for the Treatment of Pediatric NAFLD

Baseline characteristics by cohort

Measure	Gemcabene n=6 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Age, Categorical <=18 years	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Percent change in alanine aminotransferase (ALT) from baseline to 12 weeks was examined. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 units/Liter (U/L) for boys and girls aged 1-18. Children with a sustained ALT ≥ 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Percent Change in Alanine Aminotransferase (ALT)	79.86 Percent change Standard Deviation 27.02

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12.

Absolute change in ALT among study participants is reported here. ALT elevation is the most common screening test used for detecting NAFLD. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 U/L for boys and girls aged 1-18. Children with a sustained ALT ≥ 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage.

Outcome measures

Measure	Gemcabene n=4 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in ALT Baseline to Week 6	55.50 Units/Liter (U/L) Standard Deviation 49.55
Absolute Change in ALT Baseline to Week 12	80.33 Units/Liter (U/L) Standard Deviation 63.26

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12.

Percent change in ALT from baseline to week 6 and the mean of week 6 and week 12 was examined. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 U/L for boys and girls aged 1-18. Children with a sustained ALT ≥ 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage.

Outcome measures

Measure	Gemcabene n=4 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Percent Change in ALT Between Study Visits Baseline to Week 6	58.47 Percent change Standard Deviation 48.90
Percent Change in ALT Between Study Visits Week 6 to Week 12	4.58 Percent change Standard Deviation 12.31

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Hepatic steatosis (fat accumulation in the liver) was measured by MRI using liver fat fraction (HepaFat-Scan by Resonance Health). NAFLD is characterized by an accumulation of fat in the liver. Having a fat percentage greater than 5% of the weight of the liver is a typical cut point to indicate NAFLD. The HepaFat-Scan software is a non-invasive method of measuring the volumetric liver fat fraction and is validated in children.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Hepatic Steatosis	9.87 percentage of fat Standard Deviation 4.06

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of treatment.

Pancreatic fat was measured by MRI (HepaFat). Increased pancreatic fat is associated with more severe liver disease in children with NAFLD.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Pancreatic Fat	2.70 percentage of fat Standard Deviation 2.26

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12.

AST is a common screening test used for detecting NAFLD. The normal range for AST varies by age, sex, and the specific assay used but is approximately 13-32 U/L for boys and 12-24 units/Liter for girls aged 7-18. Elevated AST levels indicate increased liver disease.

Outcome measures

Measure	Gemcabene n=4 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Aspartate Aminotransferase (AST) Baseline to Week 6	17.25 Units/Liter (U/L) Standard Deviation 12.15
Absolute Change in Aspartate Aminotransferase (AST) Baseline to Week 12	30.33 Units/Liter (U/L) Standard Deviation 23.38

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Insulin sensitivity was determined by assessment of fasting insulin. Fasting insulin increases with insulin resistance and tends to occur with NAFLD.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Change in Fasting Insulin Baseline to Week 6	5.73 micro international unit per mL (uIU/mL) Standard Deviation 16.22
Change in Fasting Insulin Baseline to Week 12	16.03 micro international unit per mL (uIU/mL) Standard Deviation 20.93

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Insulin sensitivity was determined by assessment of fasting glucose. The normal range for fasting glucose in children is 70-99 mg/dL. Diabetes mellitus is indicated with fasting glucose levels of 126 or greater.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Change in Fasting Glucose Baseline to Week 6	-1.03 milligrams per deciliter (mg/dL) Standard Deviation 9.65
Change in Fasting Glucose Baseline to Week 12	-2.63 milligrams per deciliter (mg/dL) Standard Deviation 1.40

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to week 6 or week 12 and who had their blood sample analyzed.

The HOMA-IR score is calculated as fasting blood glucose level (nmol/L) multiplied by fasting insulin level (microU/L), divided by 22.5. Higher scores indicate increasing insulin resistance, although pediatric cut-points for HOMA-IR scores vary by gender and age.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score Baseline to Week 6	1.11 units on a scale Standard Deviation 4.32
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score Baseline to Week 12	3.75 units on a scale Standard Deviation 5.38

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12.

Gamma-glutamyl transferase (GGT) is a biomarker for NAFLD. Normal GGT values vary by age and the specific assay used. The normal range for males and females aged 11-18 is approximately 5-15 U/L. Increased GGT is associated with more severe NAFLD.

Outcome measures

Measure	Gemcabene n=4 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Gamma-glutamyltransferase (GGT) Baseline to Week 6	2.00 International units per liter (IU/L) Standard Deviation 3.16
Absolute Change in Gamma-glutamyltransferase (GGT) Baseline to Week 12	6.67 International units per liter (IU/L) Standard Deviation 2.31

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Blood was drawn for a clinical lipid profile, including total cholesterol. Cholesterol is waxy substance which is produced by the liver or comes from food consumed. Cholesterol concentrations are commonly used as a marker for cardiovascular disease risk in adulthood Total cholesterol levels below 170 mg/100 milliliters (mL) of blood are in the normal range while levels at 200 and above are considered high.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Total Cholesterol Baseline to Week 6	-4.00 mg/dL Standard Deviation 17.78
Absolute Change in Total Cholesterol Baseline to Week 12	-2.33 mg/dL Standard Deviation 15.31

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Blood was drawn for a clinical lipid profile, including total non-HDL-C. A measurement of non-HDL-C is obtained by subtracting high-density lipoprotein (HDL) level from total cholesterol. Non-HDL-C can predict atherosclerosis with as much accuracy as other lipoproteins can. Non-HDL-C values of 129 mg/dL or greater are considered high.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Blood was drawn for a clinical lipid profile, including total HDL cholesterol. HDL cholesterol is the "good" cholesterol because it is a type of fat that removes cholesterol from blood, thereby preventing build up. A healthy value for HDL cholesterol is 35 mg/dL and higher. Values under 35 mg/dL mean the child has a higher risk of developing heart disease.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in High-density Lipoprotein (HDL) Cholesterol Baseline to Week 6	-1.97 milligrams per deciliter (mg/dL) Standard Deviation 2.55
Absolute Change in High-density Lipoprotein (HDL) Cholesterol Baseline to Week 12	-2.97 milligrams per deciliter (mg/dL) Standard Deviation 4.96

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Blood was drawn for a clinical lipid profile, including total VLDL cholesterol. VLDL cholesterol is produced in the liver and high levels are associated with increased plaque buildup in arteries. Values of VLDL-C that are 29 mg/dL or greater are considered high.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Blood was drawn for a clinical lipid profile, including LDL cholesterol. LDL cholesterol levels below 110 mg/100 mL of blood are in the normal range while levels at 130 and above are considered high.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Low-density Lipoprotein (LDL) Cholesterol Baseline to Week 6	-1.33 milligrams per deciliter (mg/dL) Standard Deviation 18.88
Absolute Change in Low-density Lipoprotein (LDL) Cholesterol Baseline to Week 12	-2.67 milligrams per deciliter (mg/dL) Standard Deviation 12.74

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Blood was drawn for a clinical lipid profile, including triglycerides. Triglycerides are made by the body and come from food consumed. High triglyceride levels increases the risk of heart disease and stroke. Triglyceride levels below 150 mg/dL are considered acceptable while levels greater than 200 mg/dL are considered high.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Triglycerides (TG) Baseline to Week 6	-7.33 milligrams per deciliter (mg/dL) Standard Deviation 41.31
Absolute Change in Triglycerides (TG) Baseline to Week 12	31.67 milligrams per deciliter (mg/dL) Standard Deviation 7.64

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoA-1 is a component of HDL ("good cholesterol") which transports cholesterol and phospholipids through the body to the liver. Among children aged 2 to 17 years, an ApoA-1 level of less than 115 mg/dL is considered low and levels greater than 120 mg/dL are considered acceptable.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Apolipoprotein A-1 (ApoA-1) Baseline to Week 6	-2.27 milligrams per deciliter (mg/dL) Standard Deviation 10.27
Absolute Change in Apolipoprotein A-1 (ApoA-1) Baseline to Week 12	0.80 milligrams per deciliter (mg/dL) Standard Deviation 15.09

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoB is a component of VLDL, intermediate-density lipoproteins (IDL), LDL, and chylomicrons. Among children aged 2 to 17 years, an ApoB level of less than 90 mg/dL is considered acceptable and levels of 100 mg/dL and greater are considered high.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Apolipoprotein B (ApoB) Baseline to Week 6	0.90 milligrams per deciliter (mg/dL) Standard Deviation 15.02
Absolute Change in Apolipoprotein B (ApoB) Baseline to Week 12	3.07 milligrams per deciliter (mg/dL) Standard Deviation 8.19

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoC-II is a component of VLDL and chylomicrons. Normal values are between 3-5 mg/dL and abnormal values may be caused by a lipoprotein lipase deficiency resulting in fats not being broken down normally. Abnormal ApoC-II measurements may explain elevated levels of cholesterol and triglycerides.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Apolipoprotein C-II (ApoC-II) Baseline to Week 6	0.03 milligrams per deciliter (mg/dL) Standard Deviation 0.89
Absolute Change in Apolipoprotein C-II (ApoC-II) Baseline to Week 12	0.95 milligrams per deciliter (mg/dL) Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoE is a component of IDL and chylomicrons and carry cholesterol to the brain. Normal values of ApoE are between 3-7 mg/dL. Elevated ApoE may be associated with increased risk of dyslipidemia and atherosclerosis.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Apolipoprotein E (ApoE) Baseline to Week 6	0.24 milligrams per deciliter (mg/dL) Standard Deviation 0.54
Absolute Change in Apolipoprotein E (ApoE) Baseline to Week 12	0.26 milligrams per deciliter (mg/dL) Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoCIII is a component of VLDL, HDL, and triglyceride-rich chylomicrons and regulates lipid metabolism. Elevated ApoCIII is associated with atherosclerosis and cardiovascular disease.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Apolipoprotein CIII (ApoCIII) Baseline to Week 6	-1.80 mg/dL Standard Deviation 2.59
Absolute Change in Apolipoprotein CIII (ApoCIII) Baseline to Week 12	0.87 mg/dL Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis includes participants who completed the trial up to Week 6 or Week 12 and who had their blood sample analyzed.

High Sensitivity C-Reactive Protein (hsCRP) is a measurement assessing inflammation. Increased levels of hsCRP are associated with increased risk of cardiovascular disease or cardiovascular events such as stroke or heart attack. Values of hsCRP that are less than 1.0 mg/L are considered low risk, 1.0 to 3.0 mg/L indicates average risk, and values greater than 3.0 mg/L are considered high risk.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in High Sensitivity C-Reactive Protein (hsCRP) Baseline to Week 6	0.21 milligrams per liter (mg/L) Standard Deviation 0.15
Absolute Change in High Sensitivity C-Reactive Protein (hsCRP) Baseline to Week 12	1.15 milligrams per liter (mg/L) Standard Deviation 1.42

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Interleukin 1 beta is a cytokine protein involved in inflammatory response. A normal value for IL-1B is less than 3.9 picograms per milliliter (pg/mL). Increased IL-1B levels have been found to be associated with congestive heart failure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Interleukin 6 is a cytokine protein involved in the pro-inflammatory and anti-inflammatory response and stimulates an inflammatory response in many diseases, including atherosclerosis. Higher levels are generally interpreted as worsening of a disease condition.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Procollagen III peptide levels can be used to assess the degree of collagen turnover and liver fibrosis. Increases in serum concentrations of procollagen III indicate a worsening disease state.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Lipoprotein particle size will be assessed by Nuclear Magnetic Resonance (NMR). VLDL size ranges from 30-90 nanometers (nm) and is impacted by eating a meal high in fat. A linear relationship has been seen between VLDL particle size and NAFLD degree of severity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Lipoprotein particle size will be assessed by Nuclear Magnetic Resonance (NMR). HDL size ranges from 7-13 nanometers (nm). Different sizes of HDL perform different functions in the body and this study will examine how HDL particle size is altered over time by the study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Lipoprotein particle size will be assessed by Nuclear Magnetic Resonance (NMR). LDL size ranges from 21-27 nanometers (nm) and is impacted by metabolic factors. This study will examine how LDL particle size is altered over time by the study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

The size of chylomicrons in blood will be assessed throughout the study period. Chylomicrons are lipoprotein particles comprised of primarily of triglycerides and also contain phospholipids, and proteins. The size of chylomicrons varies and typically range from 75 to 600 nanometers (nm) in diameter. Chylomicrons are larger immediately following a meal.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: This analysis was not performed due to early termination of the study. Frozen samples were to be run in batches upon completion of the study, however, very few samples had been collected as the study did not reach completion. As the milestones for study completion were not met, funding for running the samples was not available.

Rate of de novo lipogenesis (DNL) will be measured using stable isotope tracers. DNL is a biochemical process occurring in the liver where fatty acids are synthesized into carbohydrates. This study will examine how the rate of DNL is altered over time by the study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Abdominal visceral fat was measured with the AMRA Medical body composition profile calculated from MRI images.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Abdominal Visceral Fat	0.66 Liters Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Abdominal subcutaneous fat was measured with the AMRA Body composition profile calculated from MRI images.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Abdominal Subcutaneous Fat	1.30 Liters Standard Deviation 0.35

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis was not performed due to early termination of the study. As the milestones for study completion were not met, funding for this analysis was not available.

LiverMultiScan by Perspectum Diagnostics is an imaging software tool that works with MRI providing a non-invasive way to diagnose liver disease. A LIF score of <1 represents a normal liver, 1-1.99 represents mild liver disease, 2-2.99 represents moderate liver disease, and a score ⩾3 represents severe liver disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

Height in centimeters was measured at each study visit.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Height	0.62 centimeters (cm) Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Weight in kilograms was measured at each study visit.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Weight	5.00 kilograms (kg) Standard Deviation 1.32

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Body mass index (BMI) was calculated as weight (in kilograms) divided by height (in meters) squared (kg/m^2). The change in BMI between Baseline and Week 12 is presented here.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Body Mass Index (BMI)	1.78 kilograms per meters^2 (kg/m^2) Standard Deviation 0.36

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Waist circumference was measured in centimeters at each study visit. The change is waist circumference between Baseline and Week 12 is presented here.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Absolute Change in Waist Circumference	5.73 centimeters (cm) Standard Deviation 6.33

SECONDARY outcome

Timeframe: Week 12

Population: This analysis includes participants completing 12 weeks of gemcabene.

Adherence was assessed by pill counts of returned bottles. A total of 120 pills were dispensed for the 12 week study period. Taking one pill per day for 12 weeks means that 36 pills would be returned if the participant had perfect adherence. Pill counts greater than 36 mean that doses were skipped.

Outcome measures

Measure	Gemcabene n=3 Participants Children with NAFLD receiving 12 weeks of treatment with gemcabene
Pill Count	52.0 Number of pills returned Standard Deviation 19.1

Adverse Events

Gemcabene

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Gemcabene n=6 participants at risk Children with NAFLD receiving 12 weeks of treatment with gemcabene
Hepatobiliary disorders Increase in liver fat percentage	50.0% 3/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
General disorders Increase in Creatine Kinase	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
Hepatobiliary disorders Elevated liver enzymes	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
General disorders Nausea	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Sinus Infection	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
Psychiatric disorders Anxiety	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.
Gastrointestinal disorders Vomitting	16.7% 1/6 • Adverse events were monitored and documented from the time of first dose of study drug (Study Day 1) until the Week 16 Follow-up Visit.

Additional Information

Miriam Vos, MD

Emory University

Phone: 404-727-9930

Email: mvos@emory.edu

Results disclosure agreements

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