Trial Outcomes & Findings for Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy (NCT NCT01679197)

NCT ID: NCT01679197

Last Updated: 2017-06-14

Results Overview

Primary outcome will be the total non-alcoholic steatohepatitis (NASH) score read histopathologically from the liver biopsy samples. This outcome measure quantifies the severity of fatty liver disease. At baseline and at the end of the year, patients have undergone a transcutaneous liver biopsy and the specimens were graded for the severity of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) pathology. Histological features of NAFLD/NASH were scored using the validated NASH-CRN (NASH Clinical Research Network) scoring system. This scoring system is the total of 4 subscales: steatosis (0-3), lobular inflammation (0-3), hepatocellular ballooning (0-2) and fibrosis (0-4), which are evaluated semi-quantitatively. The total scale range for this scoring system is 0-12, with 0 representing no features of fatty liver disease, and 12 representing the highest degree of fatty liver disease.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2017-06-14

Participant Flow

Participant milestones

Measure	Treatment Metreleptin Metreleptin
Overall Study STARTED	23
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy

Baseline characteristics by cohort

Measure	Treatment n=23 Participants Metreleptin Metreleptin
Age, Categorical <=18 years	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	42.35 years STANDARD_DEVIATION 15.82 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	22 Participants n=5 Participants
Race/Ethnicity, Customized African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized Native American	0 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants
Race/Ethnicity, Customized Decline to answer	0 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.

Primary outcome will be the total non-alcoholic steatohepatitis (NASH) score read histopathologically from the liver biopsy samples. This outcome measure quantifies the severity of fatty liver disease. At baseline and at the end of the year, patients have undergone a transcutaneous liver biopsy and the specimens were graded for the severity of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) pathology. Histological features of NAFLD/NASH were scored using the validated NASH-CRN (NASH Clinical Research Network) scoring system. This scoring system is the total of 4 subscales: steatosis (0-3), lobular inflammation (0-3), hepatocellular ballooning (0-2) and fibrosis (0-4), which are evaluated semi-quantitatively. The total scale range for this scoring system is 0-12, with 0 representing no features of fatty liver disease, and 12 representing the highest degree of fatty liver disease.

Outcome measures

Measure	Treatment n=23 Participants Metreleptin Metreleptin	Liver Function ALT	HDL Cholesterol mg/dL Lipid measurement	LDL mg/dL Lipid measurement
Liver Histopathology Baseline	6 units on a scale Standard Deviation 2	—	—	—
Liver Histopathology Month 12	5 units on a scale Standard Deviation 2	—	—	—

SECONDARY outcome

Timeframe: 1 year

Population: The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.

All enrolled patients will have a baseline MRI of the liver to evaluate liver volume and liver fat. For determination of hepatic fat content by MRI and MR spectroscopy in patients, a series of out-phase and in-phase MRI at multiple flip angles are used. By combination of out-phase and in-phase MRI at multiple flip-angles and TE times, relaxation-time effects can be removed to yield quantitative intra-hepatic (and other organs') fractional fat content throughout the liver in a few breath-hold intervals.

Outcome measures

Measure	Treatment n=23 Participants Metreleptin Metreleptin	Liver Function ALT	HDL Cholesterol mg/dL Lipid measurement	LDL mg/dL Lipid measurement
Liver Fat by MRI and MR Spectroscopy Baseline	19.19 %fat Standard Deviation 11.11	—	—	—
Liver Fat by MRI and MR Spectroscopy Month 12	13.47 %fat Standard Deviation 9.02	—	—	—

SECONDARY outcome

Timeframe: 1 year

Population: The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.

AST and ALT are the liver function tests. We are reporting the liver function tests where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.

Outcome measures

Measure	Treatment n=23 Participants Metreleptin Metreleptin	Liver Function ALT n=23 Participants	HDL Cholesterol mg/dL Lipid measurement	LDL mg/dL Lipid measurement
Liver Function Tests Baseline	41.52 IU/L Standard Deviation 27.46	53.22 IU/L Standard Deviation 37.03	—	—
Liver Function Tests Month 12	30.37 IU/L Standard Deviation 14.04	36 IU/L Standard Deviation 22.84	—	—

SECONDARY outcome

Timeframe: 1 year

Population: The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.

Cholesterol, triglycerides, HDL cholesterol, and LDL together make up the lipid profile and must be reported together. We are reporting the lipid profile where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.

Outcome measures

Measure	Treatment n=23 Participants Metreleptin Metreleptin	Liver Function ALT n=23 Participants	HDL Cholesterol mg/dL n=23 Participants Lipid measurement	LDL mg/dL n=23 Participants Lipid measurement
Fasting Lipids Baseline	256.91 mg/dL Standard Deviation 136.87	1057.48 mg/dL Standard Deviation 1744.89	35.83 mg/dL Standard Deviation 11.01	95.39 mg/dL Standard Deviation 48.30
Fasting Lipids Month 12	189.11 mg/dL Standard Deviation 64.73	478.47 mg/dL Standard Deviation 790.85	33.42 mg/dL Standard Deviation 6.41	95.95 mg/dL Standard Deviation 32.64

SECONDARY outcome

Timeframe: 1 year

Population: The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.

Outcome measures

Measure	Treatment n=23 Participants Metreleptin Metreleptin	Liver Function ALT	HDL Cholesterol mg/dL Lipid measurement	LDL mg/dL Lipid measurement
Fasting Glucose Month 12	163.53 mg/dL Standard Deviation 66.79	—	—	—
Fasting Glucose Baseline	178.91 mg/dL Standard Deviation 82.36	—	—	—

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	Treatment n=23 Participants Metreleptin Metreleptin	Liver Function ALT	HDL Cholesterol mg/dL Lipid measurement	LDL mg/dL Lipid measurement
Body Weight Baseline	77.2 kg Standard Deviation 21.4	—	—	—
Body Weight Month 12	75.0 kg Standard Deviation 23.1	—	—	—

Adverse Events

Treatment

Serious events: 7 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment n=23 participants at risk Metreleptin Metreleptin
Cardiac disorders Left shoulder pain, atypical chest pain	4.3% 1/23 • Number of events 1
Immune system disorders Granulomatous tissue reaction	4.3% 1/23 • Number of events 1
Respiratory, thoracic and mediastinal disorders Bronchial pneumonia	4.3% 1/23 • Number of events 1
Musculoskeletal and connective tissue disorders Fall, hip fracture	4.3% 1/23 • Number of events 1
Metabolism and nutrition disorders Hypertriglyceridemia	4.3% 1/23 • Number of events 1
Nervous system disorders Transient ischemic attack vs. cerebrovascular attack vs. complicated migraine	4.3% 1/23 • Number of events 1
Gastrointestinal disorders Epigastric pain, mild chest pain	4.3% 1/23 • Number of events 1
Metabolism and nutrition disorders Secondary diabetes mellitus with keatoacidosis	4.3% 1/23 • Number of events 1
Nervous system disorders Bell's palsy left side weakness	4.3% 1/23 • Number of events 1
Renal and urinary disorders UTI abdominal pain	4.3% 1/23 • Number of events 1
Surgical and medical procedures Rectal prolapse surgery	4.3% 1/23 • Number of events 1
Musculoskeletal and connective tissue disorders Chest pain	4.3% 1/23 • Number of events 1

Other adverse events

Measure	Treatment n=23 participants at risk Metreleptin Metreleptin
Blood and lymphatic system disorders Hypoglycemia	30.4% 7/23 • Number of events 12
Musculoskeletal and connective tissue disorders Muscle cramping	8.7% 2/23 • Number of events 2
General disorders Dizziness	8.7% 2/23 • Number of events 2
Immune system disorders Upper respiratory tract infection	39.1% 9/23 • Number of events 10
Gastrointestinal disorders Diarrhea	21.7% 5/23 • Number of events 6
Renal and urinary disorders Urinary tract infection	8.7% 2/23 • Number of events 3
Musculoskeletal and connective tissue disorders Fall	8.7% 2/23 • Number of events 2
Skin and subcutaneous tissue disorders Alopecia	8.7% 2/23 • Number of events 2
General disorders Nausea	13.0% 3/23 • Number of events 4
Respiratory, thoracic and mediastinal disorders Bronchitis	8.7% 2/23 • Number of events 2
Gastrointestinal disorders Vomiting	8.7% 2/23 • Number of events 3
Respiratory, thoracic and mediastinal disorders Asthma	13.0% 3/23 • Number of events 3
Renal and urinary disorders Hematuria	8.7% 2/23 • Number of events 2
Respiratory, thoracic and mediastinal disorders Cough	8.7% 2/23 • Number of events 2
Gastrointestinal disorders Abdominal pain/discomfort	13.0% 3/23 • Number of events 3
Skin and subcutaneous tissue disorders Injection site reaction	13.0% 3/23 • Number of events 3
Skin and subcutaneous tissue disorders Rash	8.7% 2/23 • Number of events 2
Infections and infestations Cold/Flu-like symptoms	17.4% 4/23 • Number of events 4

Additional Information

Dr. Elif Oral

University of Michigan

Phone: 7346157271

Email: eliforal@med.umich.edu

Results disclosure agreements

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