Trial Outcomes & Findings for Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH) (NCT NCT00596934)

NCT ID: NCT00596934

Last Updated: 2017-11-24

Results Overview

Non-alcoholic steatohepatitis (NASH) score after approximately one year of treatment with metreleptin. Total NASH scores can range from 0 to 14. The higher the NASH score the more severe the liver disease.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2017-11-24

Participant Flow

Patient recruitment occurred from February 2007 and concluded in October 2007.

One of ten enrolled participants screen failed during baseline visit, liver biopsy showed no non-alcoholic steatohepatitis. Therefore he is not included in any tables or analyses.

Participant milestones

Measure	NASH02 Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Overall Study STARTED	9
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	NASH02 Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH)

Baseline characteristics by cohort

Measure	Metreleptin Treatment Arm n=9 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Age, Continuous	44.3 years n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	9 Participants n=93 Participants
Region of Enrollment United States	9 participants n=93 Participants
Non-alcoholic steatohepatitis (NASH) score	8.1 units on a scale STANDARD_DEVIATION 3.3 • n=93 Participants
Body Weight	90.9 kg STANDARD_DEVIATION 9.0 • n=93 Participants
Liver fat percentage by Magnetic Resonance Imaging (MRI - Dixon method)	19.0 liver fat percentage STANDARD_DEVIATION 7.7 • n=93 Participants
Liver function test: Alanine aminotransferase (ALT)	50.9 IU/L STANDARD_DEVIATION 19.4 • n=93 Participants
Liver function test: Aspartate aminotransferase (AST)	33.5 IU/L STANDARD_DEVIATION 13.3 • n=93 Participants
Fasting glucose	98.1 mg/dL STANDARD_DEVIATION 7.2 • n=93 Participants
Insulin Resistance: homeostatic model assessment (HOMA)	7.4 mU/L x mg/dL STANDARD_DEVIATION 3.2 • n=93 Participants
Fasting triglycerides	129.4 mg/dL STANDARD_DEVIATION 66.2 • n=93 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Individuals who completed the year of metreleptin treatment and had follow-up liver biopsies after one year.

Non-alcoholic steatohepatitis (NASH) score after approximately one year of treatment with metreleptin. Total NASH scores can range from 0 to 14. The higher the NASH score the more severe the liver disease.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months	5 units on a scale Standard Deviation 1.73

SECONDARY outcome

Timeframe: 1 year

Population: Subjects that completed 12 months of metreleptin treatment.

Body weight (kg) after one year of treatment on metreleptin for patients that completed 12 months of metreleptin treatment.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Body Weight at 12 Months	86.4 kg Standard Deviation 9.9

SECONDARY outcome

Timeframe: 1 year

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	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months	13.7 liver fat percentage Standard Deviation 9.1

SECONDARY outcome

Timeframe: 1 year

Population: 7 subjects who completed 12 months of metreleptin treatment.

ALT value in subjects that completed 12 months of metreleptin treatment.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months	44.3 IU/L Standard Deviation 29.1

SECONDARY outcome

Timeframe: 1 year

Population: 7 subjects who completed 12 months of metreleptin treatment.

AST value in subjects that completed 12 months of metreleptin treatment.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months	34.9 IU/L Standard Deviation 13.9

SECONDARY outcome

Timeframe: 1 year

Population: 7 subjects who completed 12 months of metreleptin treatment.

Fasting glucose value in subjects that completed 12 months of metreleptin treatment.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Fasting Glucose Value at 12 Months	92.1 mg/dL Standard Deviation 5.9

SECONDARY outcome

Timeframe: 1 year

Population: 7 subjects who completed 12 months of metreleptin treatment.

Fasting triglyceride value in subjects that completed 12 months of metreleptin treatment.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Fasting Triglycerides Value at 12 Months	146.4 mg/dL Standard Deviation 75.7

SECONDARY outcome

Timeframe: 1 year

Population: 7 subjects who completed 12 months of metreleptin treatment.

HOMA values in subjects that completed 12 months of metreleptin treatment.

Outcome measures

Measure	Metreleptin Treatment Arm n=7 Participants Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Insulin Resistance: Homeostatic Model Assessment (HOMA) at 12 Months	4.1 mU/L x mg/dL Standard Deviation 3.0

Adverse Events

Metreleptin Treatment Arm

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metreleptin Treatment Arm n=9 participants at risk Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Blood and lymphatic system disorders toxoplasmosis	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.

Other adverse events

Measure	Metreleptin Treatment Arm n=9 participants at risk Treatment group metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections
Musculoskeletal and connective tissue disorders left side muscle pain	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Nervous system disorders vertigo	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Renal and urinary disorders polyuria	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Skin and subcutaneous tissue disorders actinic keratoses	11.1% 1/9 • Number of events 10 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Renal and urinary disorders haematuria	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Reproductive system and breast disorders rectal pressure with ejaculation	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Blood and lymphatic system disorders right sternocleidomastoid lymphadenopathy	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
Blood and lymphatic system disorders right axilla lymphadenopathy	11.1% 1/9 • Number of events 1 • 13 months from patient baseline appointment. Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.

Additional Information

Dr. Elif A. Oral

University of Michigan

Phone: 734-615-7271

Email: eliforal@med.umich.edu

Results disclosure agreements

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