Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy
Condition: Fatty Liver Disease, Nonalcoholic; Nonalcoholic Steatohepatitis; Lipodystrophy
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Lipodystrophy
Intervention: Metreleptin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: No
Keywords: Nonalcoholic fatty liver disease; NAFLD; Nonalcoholic steatohepatitis; NASH; Lipodystrophy; Leptin; Metreleptin; Hypertriglyceridemia; Diabetes mellitus

Summary:

      This study involves research about an investigational medicine called metreleptin. The reason
      for this study is to find out how metreleptin can improve non-alcoholic steatohepatitis or
      nonalcoholic fatty liver disease associated with lipodystrophy, a rare disorder associated
      with abnormal loss of the body's fat tissue. In this study, metreleptin is considered to be
      investigational for the treatment of lipodystrophy. Metreleptin will be given via injections
      under the skin. We plan to continue therapy for a period of one year and evaluate the change
      in liver disease by a liver biopsy. We will also follow the metabolic parameters (e.g. blood
      cholesterol, liver function, insulin resistance) and body composition characteristics (e.g.
      the pattern of fat distribution in the body).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is male or female ≥ 5 years old at baseline.

          -  Is male, female not of childbearing potential, or meets all the following criteria if
             female of childbearing potential (including perimenopausal women who have had a
             menstrual period within one year):

               -  Not breastfeeding

               -  Negative pregnancy test result (human chorionic gonadotropin, beta subunit
                  [βhCG]) at baseline (not applicable to hysterectomized females).

               -  Must practice and be willing to continue to practice appropriate birth control
                  (defined as a method which results in a low failure rate when use consistently
                  and correctly, such as implants, injectables, oral contraceptives, some
                  intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a
                  vasectomized partner) during the entire duration of metreleptin treatment.

          -  Has physician-confirmed lipodystrophy as defined by evidence of generalized (whole
             body) or partial (limbs) loss of body fat outside the range of normal variation.

          -  Alcohol consumption of less than 40 grams/week.

          -  A liver ultrasound confirming non-alcoholic fatty liver disease, or previous liver
             biopsy confirming NASH status.

          -  If ≥ 18 years of age, is able to read, understand and sign the U of M IRBMED approved
             informed consent form (ICF), communicate with study physician and study team,
             understand and comply with protocol requirements.

          -  If < 18 and ≥ 7 years of age, is able to read, understand and sign the appropriate U
             of M IRBMED approved assent form and has a parent or legal guardian that is able to
             read, understand and sign the ICF.

          -  If < 7 and ≥ 5 years of age or unable to read, the appropriate assent form must be
             explained to the child.

          -  If previously treated with thiazolidinediones or Vitamin E, stable dose of these
             medications for at least 3 months.

        Exclusion Criteria:

          -  Presence of advanced liver disease (as evidenced by abnormal synthetic function,
             abnormal PT or albumin).

          -  Evidence of other etiologies of viral hepatitis.

          -  Presence of clinically significant hematologic abnormalities (such as neutropenia
             and/or lymphadenopathy).

          -  Presence of HIV infection.

          -  Very poorly controlled diabetes; HbA1c >10%

          -  Inability to give informed consent.

          -  Presence of ESRD, any type of active cancer, or >class 2 congestive heart failure
             ((New York Heart Association Functional Classification System), based on medical
             history and physical examination.

          -  Active infection (may be transient).

          -  Has known allergies to E. coli-derived proteins or hypersensitivity to any component
             of metreleptin treatment.

          -  Any other condition in the opinion of the investigators that may impede successful
             data collection.